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Basic Science Research Related to Chiropractic Spinal Adjusting: The State of the Art and Recommendations Revisited

      Abstract

      Objective

      The objectives of this white paper are to review and summarize the basic science literature relevant to spinal fixation (subluxation) and spinal adjusting procedures and to make specific recommendations for future research.

      Methods

      PubMed, CINAHL, ICL, OSTMED, and MANTIS databases were searched by a multidisciplinary team for reports of basic science research (since 1995) related to spinal fixation (subluxation) and spinal adjusting (spinal manipulation). In addition, hand searches of the reference sections of studies judged to be important by the authors were also obtained. Each author used key words they determined to be most important to their field in designing their individual search strategy. Both animal and human studies were included in the literature searches, summaries, and recommendations for future research produced in this project.

      Discussion

      The following topic areas were identified: anatomy, biomechanics, somatic nervous system, animal models, immune system, and human studies related to the autonomic nervous system. A relevant summary of each topic area and specific recommendations for future research in each area were the primary objectives of this project.

      Conclusions

      The summaries of the literature for the 6 topic sections (anatomy, biomechanics, somatic nervous system, animal models, immune system, and human studies related to the autonomic nervous system) indicated that a significant body of basic science research evaluating chiropractic spinal adjusting has been completed and published since the 1997 basic science white paper. Much more basic science research in these fields needs to be accomplished, and the recommendations at the end of each topic section should help researchers, funding agencies, and other decision makers develop specific research priorities.

      Key indexing terms

      Chiropractors use a variety of diagnostic procedures and therapies to treat a wide array of disorders. The mode of treatment that is common to all chiropractors and most frequently used is spinal adjusting (manipulation). As a result, since the 1997 basic science white paper,
      • Brennan PC
      • Cramer GD
      • Kirstukas SJ
      • Cullum ME
      Basic science research in chiropractic: the state of the art and recommendations for a research agenda.
      there has been significant research activity evaluating the mechanisms of spinal fixation and spinal adjusting. This white paper is focused on that activity.
      The objectives of this article are: (1) to review and summarize the basic science literature relevant to spinal fixation (subluxation) and spinal adjusting procedures since the publication of the last white paper in 1997, and (2) to make specific recommendations for future research.

      Methods

      A multidisciplinary team of active basic science researchers was assembled to search the literature. The researchers represented anatomy, biomechanics, and neuroscience. PubMed, CINAHL, ICL, OSTMED, and MANTIS databases were searched for reports of basic science research (since 1995) related to spinal fixation (subluxation) and spinal adjusting (spinal manipulation [SM]). Both animal and human studies were included in the literature searches. In addition, hand searches of the reference sections of articles judged to be important by the authors were also obtained. Each author used key words they determined to be most important to their field and other related fields in designing their individual search strategy.
      Subsections for this article were chosen to reflect the most active areas of basic science research related to SM. Rather than have a section titled “Other” or “Miscellaneous,” summaries of relevant research that were not easily categorized were placed in the section to which they were most closely related. In a few instances, the results of investigations applied to more than 1 subsection. In these cases, the results were mentioned in each relevant section; however, the summaries for different subsections reflected the relevance to the topic area under discussion, and strong effort was made to avoid redundancy. The 1997 white paper had large sections discussing research in anatomy, neuroanatomy, and biomechanics. Topics such as animal models made up rather small subsections of the article. Those main areas of focus reflected the state of the science at that time. In the decade that has followed, a significant amount of basic science research related to chiropractic spinal adjusting has been conducted and the findings published in peer reviewed journals. This white paper features separate sections on research related to the somatic nervous system, animal models (including studies involving the autonomic nervous system), and human studies related to autonomic nervous system function. All of these sections describe important achievements. Biomechanical research continues to be an active field, and this new article reflects that activity. Relevant findings related to anatomy have also been published within recent years, and these are summarized. Finally, a section on studies of the immune system and chiropractic adjusting has also been included.
      The topics are covered in the following order: anatomy, biomechanics, somatic nervous system, animal models, immune system, and human studies related to the autonomic nervous system. Each topic section includes a summary of the relevant literature from 1995 to the present. The year 1995 was used to ensure that all literature not included in the 1997 white paper would be captured for this article. Included are some study summaries not directly related to chiropractic adjusting but that provide important information to research in a particular field that may influence future research related to chiropractic procedures. Specific recommendations for future research are included at the end of each topic section. When a recommendation is rather far-reaching or comprehensive, it is followed by suggested action steps to accomplish the recommendation. The topic sections and the organization and content of each is meant to provide a useful resource to new and active investigators interested in basic science research related to SM.

      Discussion

      Anatomical Research

      The topic of anatomical research will be divided into studies that relate specifically to SM (“Studies Related to SM”) and those that add detail to the understanding of the spine (“Studies Adding to the Knowledge Base of the Spine”).

      Studies Related to SM

      Gapping of the zygapophysial joints

      Dysfunction of the spine that is treated by chiropractors has been described as the vertebral subluxation complex. This complex, as described by Lantz
      • Lantz CA
      The vertebral subluxation complex.
      and Rosner,
      • Rosner AL
      has several components. These components include myologic, connective, vascular, neurologic, and lymphatic tissue involvement. Many hypothesize that a fundamental component of the vertebral subluxation complex is the development of adhesions in the zygapophysial joints (Z joints) after hypomobility of these structures
      • Janse J
      Principles and practice of chiropractic: an anthology.
      • Mooney V
      • Robertson J
      The facet syndrome.
      • Triano J
      Interaction of spinal biomechanics and physiology.
      . Spinal adjusting of the lumbar region is thought to separate the articular surfaces of the Z joints.
      • Kos J
      • Wolf J
      Les menisques intervertebraux et le role possible dans les blocages vertebraux (translation).
      • Engel R
      • Bogduk N
      The menisci of the lumbar zygapophysial joints.
      • Giles LG
      • Taylor JR
      Human zygapophyseal joint capsule and synovial fold innervation.
      This “gapping” is theoretically the action that “breaks up” adhesions. Elimination of adhesions would allow the Z joints to become more mobile, thus helping the motion segment (2 adjacent vertebrae and the ligamentous structures connecting them) to reestablish a physiologic range of motion (ROM).
      • Mooney V
      • Robertson J
      The facet syndrome.
      Although the idea that gapping the Z joints would occur during a SM and that this action would break up adhesions seems logical to those who have performed these procedures, no anatomical or physiologic evidence existed
      • Brennan PC
      • Cramer GD
      • Kirstukas SJ
      • Cullum ME
      Basic science research in chiropractic: the state of the art and recommendations for a research agenda.
      to show that gapping of the Z joints actually occurred or that adhesions in the Z joints could potentially be broken until relatively recently.
      • Cramer GD
      • Tuck NR
      • Knudsen JT
      • Fonda SD
      • Schliesser JS
      • Fournier JT
      • et al.
      Effects of side-posture positioning and side-posture adjusting on the lumbar zygapophyseal joints as evaluated by magnetic resonance imaging: a before and after study with randomization.
      • Cramer GD
      • Gregerson DM
      • Knudsen JT
      • Hubbard BB
      • Ustas LM
      • Cantu JA
      The effects of side-posture positioning and spinal adjusting on the lumbar Z joints: a randomized controlled trial with sixty-four subjects.
      Cramer et al
      • Cramer GD
      • Tuck NR
      • Knudsen JT
      • Fonda SD
      • Schliesser JS
      • Fournier JT
      • et al.
      Effects of side-posture positioning and side-posture adjusting on the lumbar zygapophyseal joints as evaluated by magnetic resonance imaging: a before and after study with randomization.
      • Cramer GD
      • Gregerson DM
      • Knudsen JT
      • Hubbard BB
      • Ustas LM
      • Cantu JA
      The effects of side-posture positioning and spinal adjusting on the lumbar Z joints: a randomized controlled trial with sixty-four subjects.
      found that in healthy volunteers, the lumbar Z joints did gap during both side-posture positioning and during chiropractic adjusting and the joints gapped significantly more during the latter procedure. However, no reports have been published by any group regarding gapping of the Z joints in the low back pain population.

      Degeneration of the z joints after hypomobility

      Paris
      • Paris S
      Anatomy as related to function and pain. Symposium on evaluation and care of lumbar spine problems.
      has reportedly identified adhesions in the Z joints after hypomobility. More recently, degenerative changes have been identified in the Z joints of rats after induced hypomobility.
      • Cramer GD
      • Fournier JT
      • Henderson CNR
      • Wolcott CC
      Degenerative changes following spinal fixation in a small animal model.
      See the section on Animal Models for further details.

      Advances in magnetic resonance imaging relevant to the spine and spinal adjusting

      Functional magnetic resonance imaging (MRI) evaluation of the spinal cord maps MRI signal changes following a specific stimulus designed to change neural activity. This procedure may become fundamental in the future workup of spinal cord injury
      • Stroman PW
      • Tomanek B
      • Krause V
      • Frankenstein UN
      • Malisza KL
      Mapping of neuronal function in the healthy and injured human spinal cord with spinal fMRI.
      and may provide intriguing possibilities to the assessment of the spinal cord following procedures such as spinal adjusting. Diffusion and perfusion MRI provides information related to the structure and function of tissue at a microscopic level and will play a more prominent role in future neurovascular imaging.
      • Valentini V
      • Gaudino S
      • Spagnolo P
      • Armenise S
      • Tartaglione T
      • Marano P
      Diffusion and perfusion MR imaging.
      As MRI at the molecular level becomes possible, opportunities for advances in research (and clinical practice) increase.
      • Rollo FD
      Molecular imaging: an overview and clinical applications.
      Research is also being done involving morphometry of the spine by means of MRI.
      • Cramer GD
      • Cantu JA
      • Dorsett RD
      • Greenstein JS
      • McGregor M
      • Howe JE
      • et al.
      Dimensions of the lumbar intervertebral foramina as determined from the sagittal plane magnetic resonance imaging scans of 95 normal subjects.
      Morphometric measurements allow for an increased ability to study the structures influenced by chiropractic adjusting.
      • Cramer GD
      • Gregerson DM
      • Knudsen JT
      • Hubbard BB
      • Ustas LM
      • Cantu JA
      The effects of side-posture positioning and spinal adjusting on the lumbar Z joints: a randomized controlled trial with sixty-four subjects.
      • Cramer GD
      • Cantu JA
      • Dorsett RD
      • Greenstein JS
      • McGregor M
      • Howe JE
      • et al.
      Dimensions of the lumbar intervertebral foramina as determined from the sagittal plane magnetic resonance imaging scans of 95 normal subjects.
      Of related interest is that direct oblique cervical MRI provides more accurate assessment of all of the borders of the cervical intervertebral foramens (IVFs) than standard sagittal MRI.
      • Cramer GD
      • Gregerson DM
      • Knudsen JT
      • Hubbard BB
      • Ustas LM
      • Cantu JA
      The effects of side-posture positioning and spinal adjusting on the lumbar Z joints: a randomized controlled trial with sixty-four subjects.

      Studies Adding to the Knowledge Base of the Spine

      Zygapophysial joints

      Between 15% and 40% of chronic low back pain is related to the Z joints.
      • Dreyer SJ
      • Dreyfuss PH
      Low back pain and the zygapophysial (facet) joints.
      The Z joint capsule receives a significant sensory innervation,
      • Cavanaugh JM
      Neural mechanisms of lumbar pain.
      • Vandenabeele F
      • Creemers J
      • Lambrichts I
      • Lippens P
      • Jans M
      Encapsulated Ruffini-like endings in human lumbar facet joints.
      much of which is probably related to nociception, that is, signaling potential or real tissue damage. The medial branches of the posterior primary divisions innervating a Z joint terminate as 1 of 3 types of sensory receptors: free nerve endings (nociceptive), complex unencapsulated nerve endings, and encapsulated nerve endings. The free nerve endings are associated with nociception. The ultrastructure of these receptors has been described.
      • Vandenabeele F
      • Creemers J
      • Lambrichts I
      • Lippens P
      • Jans M
      Encapsulated Ruffini-like endings in human lumbar facet joints.
      • McLain RF
      • Pickar JG
      Mechanoreceptor endings in human thoracic and lumbar facet joints.
      The Z joint capsules throughout the vertebral column are thought to do little to limit motion.
      • Onan OA
      • Heggeness MH
      • Hipp JA
      A motion analysis of the cervical facet joint.
      However, the capsules probably help to stabilize the Z joints during motions.
      • Boszczyk BM
      • Boszczyk AA
      • Putz R
      • Buttner A
      • Benjamin M
      • Milz S
      An immunohistochemical study of the dorsal capsule of the lumbar and thoracic facet joints.
      The gross and microscopic anatomy of the Z joint capsules has been described in detail.
      • Boszczyk BM
      • Boszczyk AA
      • Putz R
      • Buttner A
      • Benjamin M
      • Milz S
      An immunohistochemical study of the dorsal capsule of the lumbar and thoracic facet joints.
      • Yamashita T
      • Minaki Y
      • Ozaktay AC
      • Cavanaugh JM
      • King AI
      A morphological study of the fibrous capsule of the human lumbar facet joint.
      See the sections on Biomechanics and Somatic Nervous System for further details of current research related to the Z joints and spinal adjusting.

      Ligaments of the spine

      Nerve tracing techniques indicate that stretching of spinal ligaments results in “a barrage of sensory feedback from several spinal cord levels on both sides of the spinal cord.”
      • Jiang H
      Identification of the location, extent, and pathway of sensory neurologic feedback after mechanical stimulation of a lateral spinal ligament in chickens.
      The sensory information has been found to ascend to many higher (cortical) centers. Such findings provide provocative evidence that the spinal ligaments, along with the Z joint capsules, and the small muscles of the spine (interspinales, intertransversarii, and transversospinalis muscles) play an important role in mechanisms related to spinal proprioception (joint position sense) and may play a role in the neural activity related to spinal adjusting.
      • Cramer GD
      General characteristics of the spine.
      Recent work has also been done assessing the structure of spinal ligaments. The attachment sites and dimensions of the anterior and posterior longitudinal ligaments
      • Cramer GD
      • Roberts V
      • Tuck NR
      • Skogsbergh D
      • Yu SW
      Identification of the anterior longitudinal ligament on cadaveric spines and comparison with appearance on MRI.
      • Cramer GD
      • Tuck NR
      • Sapira I
      • Wilding AL
      • Knudsen T
      Morphometric evaluation of the anterior longitudinal ligament on cadaveric spines by means of magnetic resonance imaging.
      and the innervation and gross and light microscopic structure of the ligamenta flava
      • Viejo-Fuertes D
      • Liguoro D
      • Rivel J
      • Midy D
      • Guerin J
      Morphologic and histologic study of the ligamentum flavum in the thoraco-lumbar region.
      • Bucknill AT
      • Coward K
      • Plumpton C
      • Tate S
      • Bountra C
      • Birch R
      • et al.
      Nerve fibers in lumbar spine structures and injured spinal roots express the sensory neuron-specific sodium channels SNS/PN3 and NaN/SNS2.
      and iliolumbar ligaments
      • Aihara T
      • Takahashi K
      • Ono Y
      • Moriya H
      Does the morphology of the iliolumbar ligament affect lumbosacral disc degeneration?.
      have been studied in detail.
      The long posterior sacroiliac ligament may be important in transmitting loads from the lower extremity to the spine.
      • Vleeming A
      • Pool-Goudzwaard AL
      • Hammudoghlu D
      • Stoeckart R
      • Snidjers CJ
      • Mens JM
      The function of the long dorsal sacroiliac ligament: Its implication for understanding low back pain.
      The strongest fibers course from the posterior superior iliac spine to the sacrotuberous ligament, and many important structures attach to this band, including the aponeurotic attachments of the common origin of the erector spinae muscle. The ligament is tensed during counternutation of the sacrum and slackened during nutation.
      • Vleeming A
      • Pool-Goudzwaard AL
      • Hammudoghlu D
      • Stoeckart R
      • Snidjers CJ
      • Mens JM
      The function of the long dorsal sacroiliac ligament: Its implication for understanding low back pain.
      These findings are considered to be important by those involved with the study of the “kinetic chain concept” of load transmission from the lower extremity to the spine.

      The intervertebral disk and intervertebral disk degeneration

      Many relevant studies on the biology of the intervertebral disks (IVDs) have been completed in recent years. Disk degeneration is characterized by loss of fluid pressure, disruption or breakdown of collagen and proteoglycans, and sclerosis of the cartilaginous end plate and the adjacent subchondral bone. All of these hallmark signs of IVD degeneration can also occur as part of the normal aging process of the IVD. For these reasons, disk degeneration and normal aging of the disk are frequently discussed interchangeably
      • Kraemer J
      Natural course and prognosis of intervertebral disc diseases. International Society for the Study of the Lumbar Spine Seattle, Washington, June 1994.
      • Boos N
      • Weissbach S
      • Rohrback H
      • Weiler C
      • Spratt KF
      • Nerlich AG
      Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo award in basic science.
      , although the biochemical processes may be distinct. The IVD seems to age differently from other tissues, probably because of its lack of a blood supply, and the degenerative process may begin as early as 20 years of age (earlier in some cases).
      • Kraemer J
      Natural course and prognosis of intervertebral disc diseases. International Society for the Study of the Lumbar Spine Seattle, Washington, June 1994.
      In fact, certain teenagers may experience back pain because of IVD degeneration.
      • Herzog RJ
      The radiologic assessment for a lumbar disc herniation.
      There is an extremely wide variation in aging and degeneration of the IVD. Some individuals in their 70s have disks of equivalent health to some in their 30s. The aging and degenerative stages of the IVD from prenatal development through the ninth decade of life have been worked out in considerable detail at the gross and light microscopic levels.
      • Boos N
      • Weissbach S
      • Rohrback H
      • Weiler C
      • Spratt KF
      • Nerlich AG
      Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo award in basic science.
      • Brown MD
      The pathophysiology of disc disease.
      • Chandraraj S
      • Briggs CA
      • Opeskin K
      Disc herniations in the young and end-plate vascularity.
      • Gruber H
      • Hanley EJ
      Analysis of aging and degeneration of the human intervertebral disc: Comparison of surgical specimens with normal controls.
      • Hutton WC
      • Elmer WA
      • Boden SD
      • Hyons S
      • Toribatake Y
      • Tomita K
      • Hair GA
      The effect of hydrostatic pressure on intervertebral disc metabolism.
      • Horner HA
      • Urban JP
      2001 Volvo Award Winner in Basic Science Studies: effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc.
      Calcification of the IVD during the aging process is much more common than was once thought, being found in 58.3% of subjects at autopsy. Such calcification is “significantly underestimated” by conventional radiography.
      • Chen C
      • Cavanaugh JM
      • Ozaktay AC
      • Kallakuri S
      • King AI
      Effects of phospholipase A2 on lumbar nerve root structure and function.
      Several conditions promote or even possibly initiate disk degeneration. These include traumatic Schmorl's node formation, advanced aortic atherosclerosis,
      • Kauppila LI
      • McAlindon T
      • Evans S
      • Wilson PWF
      • Kiel D
      • Felson DT
      Disc degeneration/back pain and calcification of the abdominal aorta: A 25-year follow-up study in Framingham.
      and possibly, nicotine consumption.
      • Iwahashi M
      Mechanism of intervertebral disc degeneration caused by nicotine in rabbits to explicate intervertebral disc disorders caused by smoking.
      The biochemistry of IVD degeneration is also being elucidated. In this regard, extruded nucleus pulposus has been found to spontaneously produce increased amounts of many chemokines that not only initiate a series of events that decrease the size of the IVD bulge but also result in IVD degeneration.
      • Cramer GD
      General characteristics of the spine.
      • Herzog RJ
      The radiologic assessment for a lumbar disc herniation.
      • Kang JD
      • Georgescu HI
      • McIntyre-Larkin L
      • Stefanovic-Racic M
      • Donaldson WF
      • Evans CH
      Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2.
      • Kang JD
      • Stefanovic-Racic M
      • McIntyre LA
      • Georgescu HI
      • Evans CH
      Toward a biochemical understanding of human intervertebral disc degeneration and herniation: contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases.
      • Crean JKG
      • Roberts S
      • Jaffray DC
      • Eisenstein SM
      • Duance VC
      Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis.
      • Duance VC
      • Crean JK
      • Sims TJ
      • Avery N
      • Smith S
      • Menage J
      • et al.
      Changes in collagen cross-linking in degenerative disc disease and scoliosis.

      Intervertebral disk protrusion

      The normal mechanics of the IVD continue to be investigated.
      • Kraemer J
      Natural course and prognosis of intervertebral disc diseases. International Society for the Study of the Lumbar Spine Seattle, Washington, June 1994.
      • Boos N
      • Wallin A
      • Aebi M
      • Boesch C
      A new magnetic resonance imaging analysis method for the measurement of disc height variations.
      • Fennell AJ
      • Jones AP
      • Hukins DWL
      Migration of the nucleus pulposus within the intervertebral disc during flexion and extension of the spine.
      • McGill SM
      • Axler CT
      Changes in spine height throughout 32 hours of bedrest.
      • Hedman TP
      • Fernie GR
      Mechanical response of the lumbar spine to seated postural loads.
      In addition, the mechanisms involved in IVD protrusion and failure have been studied in detail
      • Herzog RJ
      The radiologic assessment for a lumbar disc herniation.
      • Hutton WC
      • Elmer WA
      • Boden SD
      • Hyons S
      • Toribatake Y
      • Tomita K
      • Hair GA
      The effect of hydrostatic pressure on intervertebral disc metabolism.
      • Salminen JJ
      • Erkintalo M
      • Laine M
      • Pentti J
      Low back pain in the young.
      • Jönsson B
      • Stromqvist B
      Motor affliction of the L5 nerve root in lumbar nerve root compression syndromes.
      • Hutton WC
      • Toribatake Y
      • Elmer WA
      • Ganey TM
      • Tomita K
      • Whitesides TE
      The effect of compressive force applied to the intervertebral disc in vivo: a study of proteoglycans and collagen.
      • Hutton WC
      • Yoon ST
      • Elmer WA
      • Li J
      • Murakami H
      • Minamide A
      • Akamaru T
      Effect of tail suspension (or simulated weightlessness) on the lumbar intervertebral disc: study of proteoglycans and collagen.
      • Lu YM
      • Hutton WC
      • Gharpuray VM
      Do bending, twisting, and diurnal fluid changes in the disc affect the propensity to prolapse? A viscoelastic finite model.
      • McGill SM
      The biomechanics of low back injury: implications on current practice in industry and the clinic.
      • Natarajan RN
      • Andersson GBJ
      The influence of lumbar disc height and cross-sectional area on the mechanical response of the disc to physiological loading.
      • Taylor JR
      Ligaments and annulus fibrosus of cervical discs.
      • Krismer M
      • Haid C
      • Behensky H
      • Kapfinger P
      • Landauer F
      • Rachbauer F
      Motion in lumbar functional spine units during side bending and axial rotation moments depending on the degree of degeneration.
      • Edwards WT
      • Ordway NR
      • Zheng Y
      • McCullen G
      • Han Z
      • Yuan HA
      Peak stresses observed in the posterior lateral annulus.
      • Kuga N
      • Kawabuchi M
      Histology of intervertebral disc protrusion: an experimental study using an aged rat model.
      , as well as the effects of changing intradiscal pressure.
      • Handa T
      • Ishihara H
      • Ohshima H
      • Osada R
      • Tsuji
      • Obata K
      Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.
      • Lotz JC
      • Colliou OK
      • Chin JR
      • Duncan NA
      • Liebenberg E
      Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study.
      • Lotz JC
      • Chin BA
      • Urban JP
      Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading.
      In addition, a set of terms to be used when describing bulging of the IVD was established by the International Society for the Study of the Lumbar Spine.
      • Andersson GBJ
      • Weinstein JN
      Disc herniation.
      This terminology included disk bulge, protrusion (tearing of some inner layers of the anulus fibrosus with the nucleus extending into the radial tear), extrusion (tearing of all layers of the anulus fibrosus allowing nuclear material to enter the vertebral canal), and sequestration (a piece of extruded nucleus breaks off of the host IVD). Much recent research related to IVD protrusion in the cervical and lumbar regions (protrusion in the thoracic region has not been studied as extensively) has found that IVD protrusion is a very dynamic process and that after approximately 1 to 3 weeks, IVD protrusion will usually begin a 2-month to 1-year process of resolution, resulting in significant resorption and, from a patient's standpoint (ie, pain), often complete remission of signs and symptoms.
      • Kraemer J
      Natural course and prognosis of intervertebral disc diseases. International Society for the Study of the Lumbar Spine Seattle, Washington, June 1994.
      • Bush K
      • Chaudhuri R
      • Hillier S
      • Penny J
      The pathomorphologic changes that accompany the resolution of cervical radiculopathy: a prospective study with repeat magnetic resonance imaging.
      • Haro H
      • Komori H
      • Okawa A
      • Murakami S
      • Muneta T
      • Shinomiya K
      Sequential dynamics of monocyte chemotactic protein–1 expression in herniated nucleus pulposus resorption.
      • Otani K
      • Arai I
      • Mao GP
      • Konno S
      • Olmarker K
      • Kikuchi S
      Experimental disc herniation.
      In fact, histologic evidence of resorption of sequestered nuclei pulposi has been found,
      • Carreon LY
      • Ito T
      • Yamada M
      • Uchiyama S
      • Takahashi HE
      • Ikuta F
      Histologic changes in the disc after cervical spine trauma: evidence of disc absorption.
      • Carreon LY
      • Ito T
      • Yamada M
      • Uchiyama S
      • Takahashi HE
      Neovascularization induced by anulus and its inhibition by cartilage endplate. Its role in disc absorption.
      and shrinkage of protruded nuclei pulposi has been seen on both computed tomography and MRI.
      • Koike Y
      • Uzuki M
      • Kokubun S
      • Sawai T
      Angiogenesis and inflammatory cell infiltration in lumbar disc herniation.
      This provides hope to patients with protruded IVDs and for those using conservative methods to treat this condition. Adenovirus-mediated transfer of genes and the resultant production of therapeutic growth factors are being investigated as a means to further study the biology of the IVD and the potential for treatment of disk degeneration
      • Nishida K
      • Kang JD
      • Gilbertson LG
      • Moon SH
      • Suh JK
      • Vogt MT
      • et al.
      Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor β1 encoding gene.
      ; however, the low vascularity of the adult IVD may preclude the effective use of gene therapy in IVD disease.
      • Boos N
      • Weissbach S
      • Rohrback H
      • Weiler C
      • Spratt KF
      • Nerlich AG
      Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo award in basic science.
      Two published studies have shown that the inhibition of tumor necrosis factor–α (TNF-α) (extruded nucleus pulposus contains high levels of TNF-α) by a monoclonal antibody (Remicade [infliximab], Centocor, Inc., Horsham, Pa) is successful in alleviating sciatica.
      • Korhonen T
      • Karppinen J
      • Malmivaara A
      • Autio R
      • Niinimki J
      • Paimela L
      • et al.
      Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.
      • Karppinen J
      • Korhonen T
      • Malmivaara A
      • Paimela L
      • Kyllönen E
      • Lindgren K-A
      • et al.
      Tumor necrosis factor–α monoclonal anti-body, infliximab, used to manage severe sciatica.
      Finally, the mechanisms of radicular pain continue to be studied.
      • Chen C
      • Cavanaugh JM
      • Ozaktay AC
      • Kallakuri S
      • King AI
      Effects of phospholipase A2 on lumbar nerve root structure and function.
      • Kayama S
      • Konno S
      • Olmarker K
      • Yabuki S
      • Kikuchi S
      Incision of the annulus fibrosus induces nerve root morphologic, vascular, and functional changes: an experimental study.
      • Ohnmeiss DD
      • Vanharanta H
      • Ekholm J
      Degree of disc disruption and lower extremity pain.
      • Takahashi K
      • Shima I
      • Porter RW
      Nerve root pressure in lumbar disc herniation.

      Innervation of IVDs

      The significant innervation of the IVDs continues to be investigated in detail.
      • Morinaga T
      • Takahashi K
      • Yamagata M
      • Chiba T
      • Tanaka K
      • Takahashi Y
      • et al.
      Sensory innervation to the anterior portion of the lumbar intervertebral disc.
      • Yukawa Y
      • Kato F
      • Kajino G
      • Nakamura S
      Groin pain associated with lower lumbar disc herniation.
      • Ohtori S
      • Takahashi Y
      • Takahashi K
      • Yamagata M
      • Chiba T
      • Tanaka K
      • et al.
      Sensory innervation of the dorsal portion of the lumbar intervertebral disc in rats.
      • Ohtori S
      • Takahashi K
      • Chiba T
      • Yamagata M
      • Sameda H
      • Moriya H
      Sensory innervation of the dorsal portion of the lumbar intervertebral discs in rats.
      Degenerated disks have been found to receive increased innervation by sensory fibers conducting nociception.
      • Coppes MH
      • Marani E
      • Thomeer RTWM
      • Groen GJ
      Innervation of “painful” lumbar discs.
      The added innervation seems to be stimulated by Schwann cells of the nerves innervating the outer aspect of the anulus fibrosus.
      • Johnson WEB
      • Evans H
      • Menage J
      • Eisenstein SM
      • El Haj A
      • Roberts S
      Immunohistochemical detection of Schwann cells in innervated and vascularized human intervertebral discs.
      Consequently, injured or degenerated disks are likely to be more sensitive to pain than normal disks.

      Unique characteristics of the cervical IVDs

      The cervical IVDs have been found to differ significantly from the lumbar disks. Rather than being made up of many lamellae, the anulus fibrosus of each cervical disk is composed of a single, crescent-shaped piece of fibrocartilage that is thick anteriorly and becomes very narrow laterally and posteriorly.
      • Mercer S
      • Bogduk N
      The ligaments and anulus fibrosis of the human adult cervical intervertebral discs.

      Range of motion studies

      Noteworthy studies measuring both the ranges of motion in various regions of the spine (eg, cervical region) and the motions between individual vertebrae continue. The latter activity has led to studies attempting to better understand the concept of coupled motions in the spine. Finally, significant findings related specifically to motions in the sacroiliac joints have also been published in recent years. These findings are summarized next.
      Although ROMs (eg, cervical ROMs) can be measured reliably,
      • Nilsson N
      • Christensen HW
      • Hartvigsen J
      The interexaminer reliability of measuring passive cervical range of motion, revisited.
      measurements made on different days of the same individual can vary considerably.
      • Christensen HW
      • Nilsson N
      Natural variation of cervical range of motion: a one-way repeated-measures design.
      Coupled motion (eg, rotation of vertebrae during lateral flexion) of spinal segments continues to be actively studied. Current investigators are finding that (1) these motion patterns are very complex; (2) all spinal motions are coupled motions; and (3) coupling differs from 1 motion segment to the next. Furthermore, consensus has not been reached on many of these motion patterns.
      • Harrison DE
      • Harrison DD
      • Troyanovich SJ
      Three-dimensional spinal coupling mechanics: part 1; a review of the literature.
      The full ROM of the sacroiliac joint is not expressed until the extremes of hip motion are reached, moving an average of 7.5° (range, 3°-17°) in the sagittal plane during full flexion and extension of the hips.
      • Smidt GL
      • Wei SH
      • McQuade K
      • Barakatt E
      • Sun T
      • Stanford W
      Sacroiliac motion for extreme hip positions.
      Motions as high as 22° to 36° have been reported in preteen and early teenage children.
      • Barakatt E
      • Smidt GL
      • Dawson JD
      • Wei SH
      • Heiss DG
      Interinnominate motion and symmetry: comparison between gymnasts and nongymnasts.
      Contraction of the left and right transversus abdominis muscles increases stiffness of the sacroiliac joint, thus potentially reducing sprains of the ligaments that protect it.
      • Richardson CA
      • Snijders CJ
      • Hides JA
      • Damen L
      • Pas MS
      • Storm J
      The relation between the transverses abdominis muscles, sacroiliac joint mechanics, and low back pain.

      Morphometric studies

      Morphometry means “measurement of an organism or its parts.” The past decade has seen many morphometric studies of various spinal structures. These studies allow for more accurate biomechanical and computer modeling (finite element analysis) studies to be performed and also allow for more accurate patient treatment protocols (surgical and manipulative) to be designed. Table 1 shows many of the morphometric studies performed since 1995, the region of the spine investigated, and the specific anatomical structure analyzed.
      Table 1Examples of notable morphometric studies since 1995
      Region of SpineStructureStudy
      CervicalArticular cartilage of C1 and odontoid related to median atlantoaxial jointEbraheim et al
      • Ebraheim NA
      • Yang H
      • Lu J
      • Biyani A
      • Yeasting RA
      Cartilage and synovium of the human atlanto-odontoid joint. An anatomic and histological study.
      Odontoid process of C2Xu et al
      • Xu R
      • Nadaud MC
      • Ebraheim NA
      • Yeasting RA
      Morphology of the second cervical vertebra and the posterior projection of the C2 pedicle axis.
      C2 PediclesKazan et al
      • Kazan S
      • Yildirim F
      • Sindel M
      • Tuncer R
      Anatomical evaluation of the groove for the vertebral artery in the axis vertebrae for atlanto-axial transarticular screw fixation technique.
      Vertebral bodies (C3-C7)Lu et al
      • Lu J
      • Ebraheim NA
      • Yang H
      • Rollins J
      • Yeasting RA
      Anatomic basis for anterior spinal surgery: surgical anatomy of the cervical vertebral body and disc space.
      Uncinate processes (C3-C7)Ebraheim et al
      • Ebraheim NA
      • Lu J
      • Biyani A
      • Brown JA
      • Yeasting RA
      Anatomic considerations for uncovertebral involvement in cervical spondylosis.
      Articular processes and facets (C3-C7)Ebraheim et al
      • Ebraheim NA
      • Xu R
      • Challgren E
      • Yeasting RA
      Quantitative anatomy of the cervical facet and the posterior projection of its inferior facet.
      Dong et al
      • Dong Y
      • Xia Hong M
      • Jiany L
      • Yuan Lin M
      Quantitative anatomy of the lateral mass of the atlas.
      Laminae (C2-C7)Xu et al
      • Xu R
      • Burger A
      • Ebraheim NA
      • Yeasting RA
      The quantitative anatomy of the laminas of the spine.
      Relationships of dorsal root ganglia within the intervertebral foraminaYabuki and Kikuchi
      • Yabuki S
      • Kikuchi S
      Positions of dorsal root ganglia in the cervical spine.
      Relationships of the sympathetic truckEbraheim et al
      • Ebraheim NA
      • Lu J
      • Yang H
      • Heck BE
      • Yeasting RA
      Vulnerability of the sympathetic trunk during the anterior approach to the lower cervical spine.
      ThoracicPediclesMcLain et al
      • McLain RF
      • Ferrara L
      • Kabins M
      Pedicle morphometry in the upper thoracic spine: limits to safe screw placement in older patients.
      Relationship of pedicle to neural structuresEbraheim et al
      • Ebraheim NA
      • Jabaly G
      • Xu R
      • Yeasting RA
      Anatomic relations of the thoracic pedicle to the adjacent neural structures.
      Articular facetsEbraheim et al
      • Ebraheim NA
      • Xu R
      • Ahmad M
      • Yeasting RA
      The quantitative anatomy of the thoracic facet and the posterior projection of its inferior facet.
      Boyle et al
      • Boyle JJW
      • Singer KP
      • Milne N
      Morphological survey of the cervicothoracic junctional region.
      LumbarPediclesMitra et al
      • Mitra SR
      • Datir SP
      • Jadhav SO
      Morphometric study of the lumbar pedicle in the Indian population as related to pedicular screw fixation.
      Relationship of pedicle to neural structuresEbraheim et al
      • Ebraheim NA
      • Xu R
      • Darwich M
      • Yeasting RA
      Anatomic relations between the lumbar pedicle and the adjacent neural structures.
      Pars interarticularisEbraheim et al
      • Ebraheim NA
      • Lu J
      • Hao Y
      • Biyani A
      • Yeasting RA
      Anatomic considerations of the lumbar isthmus.
      Intervertebral foraminaCramer et al
      • Cramer GD
      • Cantu JA
      • Dorsett RD
      • Greenstein JS
      • McGregor M
      • Howe JE
      • et al.
      Dimensions of the lumbar intervertebral foramina as determined from the sagittal plane magnetic resonance imaging scans of 95 normal subjects.
      Ventral rami of the lumbosacral plexusEbraheim et al
      • Ebraheim NA
      • Lu J
      • Biyani A
      • Huntoon M
      • Yeasting RA
      The relationship of lumbosacral plexus to the sacrum and the sacroiliac joint.
      SacrumCortical bone densityEbraheim et al
      • Ebraheim NA
      • Sabry FF
      • Nadim Y
      • Xu R
      • Yeasting RA
      Internal architecture of the sacrum in the elderly. An anatomic and radiographic study.
      Location of dorsal root gangliaEbraheim and Lu
      • Ebraheim NA
      • Lu J
      Morphometric evaluation of the sacral dorsal root ganglia.
      Kikuchi et al
      • Kikuchi S
      • Sato K
      • Konno S
      • Hasue M
      Anatomic and radiographic study of dorsal root ganglia.
      Sacroiliac joint (plane of articulation)Ebraheim et al
      • Ebraheim NA
      • Mekhail AO
      • Wiley WF
      • Jackson WT
      • Yeasting RA
      Radiology of the sacroiliac joint.
      Certain anatomical findings can best be discussed with each spinal region. The following sections describe anatomical findings of particular significance in the cervical, thoracic, lumbar, and sacroiliac regions. Each of the topics discussed is related to an active area of research.

      Anatomical Findings of Clinical Significance by Spinal Region: Cervical Region

      Connective tissue attachments to the spinal dura mater

      Connective tissue attachments to the posterior aspect of the spinal dura arising from the foramen magnum, posterior arch of C1, the spinous process of C2,
      • Von Lanz T
      Uber die Ruckenmarkshaute. I. Die konstruktive Form der harten Haut des menschlichen Ruckenmarkes und ihrer Bander.
      the rectus capitis posterior minor muscle,
      • Hack GD
      • Koritzer RT
      • Robinson WL
      • Hallgren RC
      • Greenman PE
      Anatomic relation between the rectus capitis posterior minor muscle and the dura mater.
      • Hack GD
      • Koritzer RT
      • Robinson WL
      • Hallgren RC
      • Greenman PE
      In response.
      • Zumpano MP
      • Jagos CS
      • Hartwell-Ford S
      A cadaveric survey exploring the variation, prevalence, sex bias, and tissue type of the soft tissue bridge between rectus capitis posterior minor and the posterior atlanto-occipital membrane.
      the ligamentum nuchae,
      • Mitchell BS
      • Humphreys BK
      • O'Sullivan E
      Attachments of the ligamentum nuchae to cervical posterior spinal dura and the lateral part of the occipital bone.
      • Humphreys BK
      • Kenin S
      • Hubbard BB
      • Cramer GD
      Investigation of connective tissue attachments to the cervical spinal dura mater.
      and the ligamenta flava between C1-C2 and C6-C7
      • Shinomiya K
      • Dawson J
      • Spengler DM
      • Konrad P
      • Blumenkopf B
      An analysis of the posterior epidural ligament role on the cervical spinal cord.
      • Shinomiya K
      • Sato T
      • Spengler DM
      • Dawson J
      Isolated muscle atrophy of distal upper extremity in spinal compression disorders.
      have been described. These attachments may hold the dura mater posteriorly during cervical extension (to prevent buckling of the dura mater into the spinal cord) and flexion (to prevent the dura from moving forward and compressing the cord). Some authors have speculated that increased tension of the cervical paraspinal muscles may traction the connection between the rectus capitis posterior minor muscle and the dura, leading to headaches secondary to dural tension.
      • Alix ME
      • Bates DK
      A proposed etiology of cervicogenic headache: the neurophysiologic basis and anatomic relationship between dura mater and the rectus posteriorcapitis minor muscle.
      Others have proposed that tearing of these connective tissue attachments during the flexion component of flexion-extension (whiplash) type of injuries or other trauma to the cervical region could lead to buckling of the dura mater into the cervical segments of the spinal cord. Such dural buckling could conceivably result in the chronic neck pain, headaches, disorders of balance, and signs and symptoms of cervical myelopathy experienced by some patients who have had trauma to the cervical region.
      • Mitchell BS
      • Humphreys BK
      • O'Sullivan E
      Attachments of the ligamentum nuchae to cervical posterior spinal dura and the lateral part of the occipital bone.
      The experimental work of Shinomiya et al
      • Shinomiya K
      • Dawson J
      • Spengler DM
      • Konrad P
      • Blumenkopf B
      An analysis of the posterior epidural ligament role on the cervical spinal cord.
      • Shinomiya K
      • Sato T
      • Spengler DM
      • Dawson J
      Isolated muscle atrophy of distal upper extremity in spinal compression disorders.
      lends support to these theories. In addition, homologous attachments in the lumbar region, called meningovertebral ligaments, have been shown to traction the dura mater and the related nerve roots after IVD protrusion.

      Vertebral artery

      The structure of the vertebral artery continues to be studied. The tortuosity of the vertebral artery can occasionally increase with severe, multilevel IVD degeneration.
      • Oga M
      • Yuga I
      • Terada K
      • Shimizu A
      • Sugioka Y
      Tortuosity of the vertebral artery in patients with cervical spondylotic myelopathy: risk factor for the vertebral artery injury during anterior cervical decompression.
      Haynes et al
      • Haynes MJ
      • Cala LA
      • Melsom A
      • Mastaglia FL
      • Milne N
      • McGeachie JK
      Vertebral arteries and cervical rotation: modeling and magnetic resonance angiography studies.
      found that usually, there is no compression or stenosis of the vertebral artery with atlantoaxial rotation. Li et al
      • Li YK
      • Zhang YK
      • Lu CM
      • Zhong SZ
      Changes and implications of blood flow velocity of the vertebral artery during rotation and extension of the head.
      found that extreme extension and extension with rotation resulted in decreased flow in both vertebral arteries. Licht et al
      • Licht P
      • Christensen HW
      • Hojgaard P
      • Hoilund-Carlsen PF
      Triplex ultrasound of vertebral artery flow during cervical rotation.
      found a decrease in flow in the vertebral artery contralateral to rotation and, for the first time, documented an increase in flow on the ipsilateral side of rotation. Mitchell et al
      • Mitchell BS
      • Humphreys BK
      • O'Sullivan E
      Attachments of the ligamentum nuchae to cervical posterior spinal dura and the lateral part of the occipital bone.
      found a decrease in flow through both the left and right vertebral arteries (more in the contralateral vessel) with maximal rotation, especially in those arteries with underlying pathology (eg, atherosclerosis). Therefore, maximal rotation and extension seem to decrease flow through the vertebral arteries, but submaximal rotation seems to have less of an effect.

      Anatomical Findings of Clinical Significance by Spinal Region: Thoracic Region

      Idiopathic Scoliosis

      The cause of idiopathic scoliosis remains unknown, but it is thought to be the result of many factors. A genetic component
      • Kesling KL
      • Reinker KA
      Scoliosis in twins: a meta-analysis of the literature and report of six cases.
      • Lowe TG
      • Edgar M
      • Margulies JY
      • Miller NH
      • Raso VJ
      • Reinker KA
      Etiology of idiopathic scoliosis: current trends in research.
      to the disorder is likely with secondary factors that include a decrease in melatonin production
      • Kanemura T
      • Kawakami N
      • Deguchi M
      • Mimatsu K
      • Iwata H
      Natural cause of experimental scoliosis in pinealectomized chickens.
      • Wang X
      • Jiang H
      • Raso J
      • Moreau M
      • Mahood J
      • Zhao J
      • Bagnall K
      Characterization of the scoliosis that develops after pinealectomy in the chicken and comparison with adolescent idiopathic scoliosis in humans.
      • Cheung KMC
      • Zhang YG
      • Lu DS
      • Luk KDKM
      • Leong JCY
      Effect of melatonin suppression on scoliosis development in chickens by either constant light or surgical pinealectomy.
      and a related increase in circulating levels of the hormone calmodulin.
      • Lowe TG
      • Edgar M
      • Margulies JY
      • Miller NH
      • Raso VJ
      • Reinker KA
      Etiology of idiopathic scoliosis: current trends in research.
      Changes in skeletal muscle,
      • Carpintero P
      • Mesa M
      • Garcia J
      • Carpintero A
      Scoliosis induced by asymmetric lordosis and rotation.
      connective tissue
      • Crean JKG
      • Roberts S
      • Jaffray DC
      • Eisenstein SM
      • Duance VC
      Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis.
      • Duance VC
      • Crean JK
      • Sims TJ
      • Avery N
      • Smith S
      • Menage J
      • et al.
      Changes in collagen cross-linking in degenerative disc disease and scoliosis.
      , bone density, rib distortion,
      • Lowe TG
      • Edgar M
      • Margulies JY
      • Miller NH
      • Raso VJ
      • Reinker KA
      Etiology of idiopathic scoliosis: current trends in research.
      decreased height of the posterior vertebral arch,
      • Deane G
      • Duthie RB
      A new projectional look at articulated scoliotic spines.
      asymmetry of the neurocentral synchondrosis,
      • Vital J
      • Beguiristain JL
      • Algara C
      • Villas C
      • Lavignolle B
      • Grenier N
      • Senegas J
      The neurocentral vertebral cartilage: anatomy, physiology, and physiopathology.
      and the relatively common finding (up to 26%) of syrinx formation and other neuroanatomical abnormalities in the spinal cord
      • Evans SC
      • Edgar MA
      • Hall-Craggs MA
      • Powell MP
      • Taylor BA
      • Noordeen HH
      MRI of ‘idiopathic’ juvenile scoliosis: a prospective study.
      • Ghanem IB
      • Londono C
      • Delalande O
      • Dubousset JF
      Chiari I malformation associated with syringomyelia and scoliosis.
      are probably the result of the altered biomechanics of the spine and spinal cord that occur with spinal curvatures.
      • Lowe TG
      • Edgar M
      • Margulies JY
      • Miller NH
      • Raso VJ
      • Reinker KA
      Etiology of idiopathic scoliosis: current trends in research.
      In addition, increasing evidence exists supporting the theory that the primary disorder (probably related to genetic influences) is the involvement of high (cortical) brain centers involved in processing vestibular information.
      • Woods LA
      • Heller RJ
      • Hansen PD
      • Fukumoto DE
      • Herman RM
      Decreased incidence of scoliosis in hearing impaired children.
      • Dias RC
      • Miller F
      • Dabney K
      • Lipton GE
      Revision spine surgery in children with cerebral palsy.
      • Theiss SM
      • Smith MD
      • Winter RB
      The long-term follow-up of patients with Klippel-Feil syndrome and congenital scoliosis.
      An interesting study by D'Attilio et al
      • D'Attilio M
      • Filippi MR
      • Femminella B
      • Festa F
      • Tecco S
      The influence of an experimentally-induced malocclusion on vertebral alignment in rats: a controlled pilot study.
      may indicate that there could be more than 1 subpopulation of patients with idiopathic scoliosis. These investigators showed that the alignment of the spinal column may be strongly influenced by dental occlusion and temporomandibular joint disturbance. These investigators reported that all 15 rats in an experimental group with an induced malocclusion developed thoracolumbar scoliosis within 1 week after the intervention. The scoliotic curvature was then completely resolved in 83% of these rats 1 week after correction of the malocclusion. None of the 15 untreated control rats in their study developed scoliosis. They suggested that an anatomical and functional relationship between the stomatognathic apparatus and the spinal column could explain their observations. They noted the presence of convergent sensory inputs to the craniocervical cord from stomatognathic and cervical spine structures and posited that a consequential tilt of the first cervical vertebra (C1) could affect the alignment of adjacent vertebrae, destabilizing the vertical alignment of the spine.

      Anatomical Findings of Clinical Significance by Spinal Region: Lumbar Region

      Many of the findings described previously in the section entitled “Intervertebral Disk” were related to the lumbar IVDs and will not be repeated here.

      Lumbar intervertebral foramina

      Transforaminal ligaments of the IVF can be identified on MRI, with a positive predictive value of 86.7%.
      • Cramer GD
      • Skogsbergh DR
      • Bakkum BW
      • Winterstein JF
      • Yu S
      • Tuck NR
      Evaluation of transforaminal ligaments by magnetic resonance imaging.
      These ligaments are present in approximately 60.0% of lumbar IVFs (66.7% of L5-S1 IVFs)
      • Cramer GD
      • Skogsbergh DR
      • Bakkum BW
      • Winterstein JF
      • Yu S
      • Tuck NR
      Evaluation of transforaminal ligaments by magnetic resonance imaging.
      and have been implicated as both a cause of low back pain and nerve root entrapment.
      • Bachop W
      • Janse J
      The corporotransverse ligament at the L5 intervertebral foramen.
      • Giles LGF
      • Macnab I
      • McCulloh J
      • Olsewski JM
      • Simmons EH
      • Kallen FC
      • Mendel FC
      Evidence from cadavers suggestive of entrapment of fifth lumbar spinal nerves by lumbosacral ligaments.
      • Transfeldt EE
      • Robertson D
      • Bradford DS
      Ligaments of the lumbosacral spine and their role in possible extraforaminal spinal nerve entrapment and tethering.
      These structures can be quite sturdy (especially at the L5-S1 region) and can calcify.
      • Wang J
      • Maniwa S
      • Winterstein J
      • Cramer GC
      • Glimcher MJ
      Composition of the corporotransverse ligaments of the lumbar L5-S1 IVFs.
      They have been found to decrease the dimensions of the compartment transmitting the anterior primary division of the spinal nerve by 31.5%.
      • Bakkum B
      • Mestan M
      The effects of transforaminal ligaments on the sizes of T11 to L5 human intervertebral foramina.
      Limiting the size of the compartment in this way may, at times, contribute to the incidence of neurologic symptoms in the region, especially after trauma or secondary to degenerative arthritic changes in the region of the IVF.
      • Bakkum B
      • Mestan M
      The effects of transforaminal ligaments on the sizes of T11 to L5 human intervertebral foramina.

      Anatomical Findings of Clinical Significance by Spinal Region: Sacroiliac Joints

      Acquired accessory sacroiliac joints frequently (19.1%) form within the posterior (fibrous) portion of the joint. These accessory joints are more common in obese and older individuals and are also associated with other signs of degeneration and periodic low back pain.
      • Prassopoulos PK
      • Faflia CP
      • Voloudaki AE
      • Gourtsoyiannia NC
      Sacroiliac joints: anatomical variants on CT.

      Recommendations

      • 1.
        Continue to investigate the effects of spinal adjusting on the tissues of the spine and other organ systems (see section on Autonomic Nervous System) in various disease states (eg, gapping studies of the Z joints).
      • 2.
        Continue to evaluate the causes of hypomobility of vertebral segments in the general population, under what conditions such hypomobility is maintained, and continue to characterize the changes of the tissues of the spine after hypomobility (and possibly hypermobility) when normal activity is reestablished (ie, normal forces to the spine are reestablished) and also after spinal adjusting is added in an attempt to help reestablish normal forces and movement to hypomobile tissues. A combination of human and animal studies will be needed to achieve this recommendation.
      • 3.
        Evaluate the effects of spinal manipulative procedures on pain of radicular origin and on radiating pain.
      • 4.
        Further evaluation at the basic science level of the issue of vertebral and basilar artery iatrogenic pathology is warranted.
      • 5.
        Conduct descriptive studies to clarify regional differences (ie, between the cervical, thoracic, and lumbar regions) in the anatomy of the vertebral column and related spinal tissues.
      • 6.
        Conduct studies evaluating the normal development of all spinal tissues from embryogenesis through the mid 20s.
      • 7.
        Conduct studies further evaluating the aging spine (fourth through ninth decades).
      • 8.
        All of the recommendations above should be carried out in both human and animal studies at the gross (imaging and postmortem studies), light microscopic (biopsy specimens, eg, those obtained during surgery, cadaveric studies), and electron microscopic (biopsy specimens and postmortem studies) levels.

      Biomechanics

      Biomechanics is the study of the effects of loads applied to biologic cells, tissues or systems. Biomechanics has its origins from Galileo's studies of mechanics in general and his creation of the term mechanics as a subtitle of his book Two New Sciences (1638) to refer to force, displacement, and strength of materials. Arguably, the “father of biomechanics” is Giovanni Alfonso Borelli, who published in De Motu Animalium (1681) the principles of muscle movements based on statics and dynamics. However, the word “biology” and its concept as the study of living organisms did not occur until 1802 when the German naturalist, Gottfried Reinhold Treviranus, published his first volume Biologie; oder die Philosophie der lebenden Natur. To rigorously understand SM and its effects requires an understanding of the principles of biomechanics.

      Manipulation Forces

      Since the publication of the first white paper in 1997, there have been several important studies that have further clarified the loads that are applied during SM, and especially during high-velocity, low-amplitude (HVLA) SM. Triano and Shultz
      • Triano J
      • Schultz AB
      Loads transmitted during lumbosacral spinal manipulative therapy.
      measured the total force that was transmitted through the body during a side-lying lumbar or lumbosacral HVLA SM. The transmitted forces were similar to the applied forces for their temporal history, but the transmitted forces and moments were shown to vary substantially based on patient positioning. Herzog et al
      • Herzog W
      • Kats M
      • Symons B
      The effective forces transmitted by high-speed, low-amplitude thoracic manipulation.
      measured the force distribution during thoracic HVLA SM and concluded that there was an important distinction between the total and effective applied forces, with the latter being much smaller than the total applied force. They found that the total peak force was being applied over a mean contact area of 34.8 cm2, but for the thoracic spine, the physiologic contact area of the transverse processes was only 0.25 cm2 (less than 1/100 of the total contact region). Hence, most of the total peak force was being applied to soft tissues (eg, skin, muscle, and fat), and only a small portion (∼5 N) was being applied to the transverse process. A similar finding was reported by Kirstukas and Backman,
      • Kirstukas SJ
      • Backman JA
      Physician-applied contact pressure and table force response during unilateral thoracic manipulation.
      who reported that the “intense contact area” was on the order of 10 cm2 during thoracic HVLA SM. Clearly, the effective applied force during HVLA SM in general will vary based on the contact area of the manipulator's hand and the aspect of the vertebra, but in general, the effective force will be less, and sometimes substantially so, than the applied force.
      The 3-dimensional force applied during HVLA SM of the cervical, thoracic, and sacroiliac regions has now been measured.
      • Van G
      • Zoest G
      • Gosselin G
      Three-dimensionality of direct contact forces in chiropractic spinal manipulative therapy.
      The 3-dimensional data showed that forces in plane with the back (ie, Fx and Fy or shearing forces) always occurred during the SM, which was dominated by the normal (ie, Fz or perpendicular) applied force. The shearing forces were considerable in magnitude, ranging from a low mean of 15% (at T4-5) to a high of 29% (at sacroiliac) of the peak Fz force. As has been previously reported by others,
      • Cohen E
      • Triano JJ
      • McGregor M
      • Papakyriakou M
      Biomechanical performance of spinal manipulation therapy by newly trained vs. practicing providers: does experience transfer to unfamiliar procedures?.
      there was a consistent drop in the preload force magnitude just before the impulse portion of the HVLA SM, which is speculated to be due to a “countermovement” affect.
      The role of sex in developing force magnitude has been investigated.
      • Forand D
      • Drover J
      • Suleman Z
      • Symons B
      • Herzog W
      The forces applied by female and male chiropractors during thoracic spinal manipulation.
      The only previous report that compared male and female manipulators found no significant differences during HVLA SM using a patient simulator.
      • Adams AA
      • Wood J
      Forces used in selected chiropractic adjustments of the low back: a preliminary study.
      Forand et al
      • Forand D
      • Drover J
      • Suleman Z
      • Symons B
      • Herzog W
      The forces applied by female and male chiropractors during thoracic spinal manipulation.
      used an experienced matched group (range, 1-24.5 year of experience) of female and male chiropractors (14 per group) and found that there were no significant differences between sexes in thoracic HVLA SM forces. The one exception was that, in the lower thoracic spine, men applied significantly greater preload than did women.
      Another type of SM is mobilization or low-velocity low-amplitude SM, which is commonly used by physical therapists as well as other health professionals, including chiropractors. The general approach is to apply an increasing force over 5 to 10 seconds to determine the “end feel,” and then so calibrated, to apply a slow oscillation (∼1 Hz for 10 seconds) about a mean graded force (I-IV arbitrary scale), which is less than the end feel.
      • Harms MC
      • Bader DL
      Variability of forces applied by experienced therapists during spinal mobilization.
      Using an instrumented mobilization table, it was found that there was considerable variation in the force magnitudes used by experienced therapists for end feel, as well as grades I-IV mobilizations of L3 vertebra in healthy subjects.
      • Harms MC
      • Bader DL
      Variability of forces applied by experienced therapists during spinal mobilization.
      When comparing treatment of younger vs older healthy subjects, it was found that, although mean forces were similar, smaller amplitudes and higher frequency of oscillations were used with older patients.
      • Harms MC
      • Innes SM
      • Bader DL
      Forces measured during spinal manipulative procedures in two age groups.
      In a study of patients with nonspecific low back pain, there was considerable variation in the magnitudes of forces used, but the variation was strongly influenced not by the patient's severity of complaint but by the physical therapist's training.
      • Chiradejnant A
      • Latimer J
      • Maher CG
      Forces applied during manual therapy to patients with low back pain.

      Effects of External Loading on Vertebral Displacements

      Our understanding of the kinematics of SM has been increased by 2 different types of investigations. First, Keller et al
      • Keller TS
      • Colloca CJ
      • Fuhr AW
      Validation of the force and frequency characteristics of the activator adjusting instrument: effectiveness as a mechanical impedance measurement tool.
      • Keller TS
      • Colloca CJ
      • Fuhr AW
      In vivo transient vibration assessment of the normal human thoracolumbar spine.
      • Keller TS
      • Colloca CJ
      • Gunzburg R
      Neuromechanical characterization of in vivo lumbar spinal manipulation. I. Part, Vertebral motion.
      have published 2 studies using mechanical force, manually assisted, short-lever SM (ie, Activator [Activator Methods International, Phoenix, Ariz] or very HVLA [VHVLA]) in vivo on patients undergoing lumbar surgery. Using forces ranging from 30 N (lowest setting) to 150 N (maximum setting) on the adjusting instrument, the vertebra where the force was applied had peak displacements of approximately 0.5 mm occurring within 10 milliseconds. Intersegmental displacements occurred of similar magnitudes but with large oscillations lasting 2 to 3 times longer (ie, 20-30 milliseconds), but all oscillations appeared to have damped out within 100 milliseconds. In a second in vivo study, they found that the vertebral displacements due to the Activator instrument were slightly larger (mean, ∼0.62 mm) and did not vary significantly, depending on whether the instrument was positioned over the spinous process or facet joint (left or right).
      • Colloca CJ
      • Keller TS
      • Gunzburg R
      Biomechanical and neurophysiological responses to spinal manipulation in patients with lumbar radiculopathy.
      Second, using intact cadaveric human lumbar spine specimens, Ianuzzi and Khalsa
      • Ianuzzi A
      • Khalsa PS
      Comparison of human lumbar facet joint capsule strains during simulated high velocity, low amplitude spinal manipulation versus physiological motions.
      simulated lumbar HVLA SM while measuring vertebra kinematics and facet joint capsule strain. During simulated HVLA SM, the applied loads were within the range measured during in vivo HVLA SM. Vertebral translations occurred primarily in the direction of the applied load and were similar in magnitude (on order of 1-2 mm) regardless of manipulation site. Vertebral rotations (on order of 1°-3°) and facet joint capsule strain magnitudes (on order of 5%) during simulated HVLA SM were within the range that occurred during physiologic motions.
      • Ianuzzi A
      • Little JS
      • Chiu JB
      • Baitner A
      • Kawchuk G
      • Khalsa PS
      Human lumbar facet joint capsule strains: I. During physiological motions.
      At a given facet joint capsule, distal manipulations induced capsule strains similar in magnitude to those that occurred when the manipulation was applied proximally.
      The mobility of lumbar vertebrae in healthy volunteers during mobilization has been assessed using dynamic MRI. Powers et al
      • Powers CM
      • Kulig K
      • Harrison J
      • Bergman G
      Segmental mobility of the lumbar spine during a PA mobilization: assessment using dynamic MRI.
      found that applying a 10-second grade IV posterior to anterior (PA) mobilization (∼100 N force) at the spinous process of a lumbar vertebra produced an extension of the vertebra ranging from a mean of 1.2° at L2 to 3.0° at L5. Using plain film radiographs, Lee and Evans
      • Lee R
      • Evans J
      An in vivo study of the intervertebral movements produced by posterioanterior mobilization.
      found similar displacements for a 150 N PA mobilization at L4. Kulig et al,
      • Kulig K
      • Landel R
      • Powers CM
      Assessment of lumbar spine kinematics using dynamic MRI: a proposed mechanism of sagittal plane motion induced by manual posterior-to-anterior mobilization.
      also using dynamic MRI, found that applying a PA mobilization induced intersegmental motion in all lumbar vertebrae, caudal and cranial, to the site of applied force. This is consistent with the findings of Ianuzzi and Khalsa
      • Ianuzzi A
      • Khalsa PS
      Comparison of human lumbar facet joint capsule strains during simulated high velocity, low amplitude spinal manipulation versus physiological motions.
      who also found that simulated HVLA SM at a single vertebra induced motion in all other lumbar vertebrae. Thus, it is not possible to move only a single vertebrae with SM (high or low velocity) because the spine is a linked and coupled structure.

      Other effects

      HVLA SM is commonly associated with a “cracking” sound, which has previously been shown to be associated with a cavitation phenomenon in the facet joints.
      • Herzog W
      • Zhang YT
      • Conway PJ
      • Kawchuk GN
      Cavitation sounds during spinal manipulative treatments.
      • Gal JM
      • Herzog W
      • Kawchuk GN
      • Conway PJ
      • Zhang YT
      Forces and relative vertebral movements during SMT to unembalmed post-rigor human cadavers: peculiarities associated with joint cavitation.
      In healthy volunteers, Ross et al
      • Ross JK
      • Bereznick DE
      • McGill SM
      Determining cavitation location during lumbar and thoracic spinal manipulation: is spinal manipulation accurate and specific?.
      found that single HVLA SM were typically associated with multiple cavitations (ranging from 2 to 6), which were from nearby vertebrae. This was consistent with the findings of Beffa and Mathews,
      • Beffa R
      • Mathews R
      Does the adjustment cavitate the targeted joint? An investigation into the location of cavitation sounds.
      who found no significant relationship between the location of the cavitation and HVLA SM of the L5 or sacroiliac joint in asymptomatic volunteers. There is some question as to whether HVLA SM can actually induce motion into the sacroiliac joint, as Tullberg et al,
      • Tullberg T
      • Blomberg S
      • Branth B
      • Johnsson R
      Manipulation does not alter the position of the sacroiliac joint. A roentgen stereophotogrammetric analysis.
      using stereo radiography, were unable to measure any significant motion of the sacrum relative to the ilium after a combination of HVLA and mobilization SM in patients with “subluxated” sacroiliac joints. Furthermore, Flynn et al
      • Flynn TW
      • Fritz JM
      • Wainner RS
      • Whitman JM
      The audible pop is not necessary for successful spinal high-velocity thrust manipulation in individuals with low back pain.
      found no association between an “audible pop” and improvement in ROM, pain, or disability in patients with nonradicular low back pain.

      Measures of Pathologic States

      An intriguing question has begun to be answered relating to whether changes in intersegmental stiffness can be discerned using clinically available tools. Colloca et al
      • Colloca CJ
      • Keller TS
      • Peterson TK
      • Seltzer DE
      Comparison of dynamic posteroanterior spinal stiffness to plain film radiographic images of lumbar disk height.
      measured intersegmental impedance (dynamic stiffness) of lumbar vertebrae and correlated it with characteristics of vertebral height and IVD height measured from plain film radiographs. They found that there was a correlation between decreased disk height at L5-S1 and increased dynamic stiffness at the same segment. These findings were analogous to those of Kaigle et al
      • Kaigle A
      • Ekstrom L
      • Holm S
      • Rostedt M
      • Hansson T
      In vivo dynamic stiffness of the porcine lumbar spine exposed to cyclic loading: influence of load and degeneration.
      who, using a porcine model, also observed increased spine dynamic stiffness associated with degenerated disks, compared with normal controls.
      Using ultrasound indentation, another noninvasive approach, Kawchuk et al
      • Kawchuk GN
      • Kaigle AM
      • Holm SH
      • Rod FO
      • Ekstrom L
      • Hansson T
      The diagnostic performance of vertebral displacement measurements derived from ultrasonic indentation in an in vivo model of degenerative disc disease.
      also found that IVD degeneration in a porcine model resulted in decreased indentation for the same applied load. This is an analogous metric as spine stiffness. The use of ultrasound indentation in this animal model had high sensitivity (75.0%), specificity (83.3%), and accuracy (77.1%), compared with other approaches (arthroscopy, MRI, and plain film radiography).
      Two biomechanics studies have been performed to examine the effects of fixation (ie, a hypomobile subluxation) of the lumbar spine. Cramer et al
      • Cramer GD
      • Fournier JT
      • Henderson CNR
      • Wolcott CC
      Degenerative changes following spinal fixation in a small animal model.
      used a rat model of fixation in the lumbar spine by externally fixating the spinous processes of L4-L6 for up to 8 weeks. A principal finding due to the fixation was the development of osteophytes and degenerative articular changes of the facet joints within a few weeks. Reversal of some of the degeneration was observed for joints that were fixated for a short term (∼1 week), but after 4 weeks, no reversal was observed. Little et al
      • Little JS
      • Ianuzzi A
      • Chiu JB
      • Baitner A
      • Khalsa PS
      Human lumbar facet joint capsule strains: II. Alteration of strains subsequent to anterior interbody fixation.
      simulated a hypomobile subluxation in intact, cadaveric human lumbar spine specimens by screwing a plate into the left anterior aspect of the L4 and L5 vertebral bodies. During physiologic motions of the fixated spine specimens for flexion, extension, and lateral bending, the motions at L4-5 were significantly decreased, whereas below and above that level, intersegmental motions were significantly increased. Correspondingly, the plane strains of the facet joint capsules were significantly decreased and increased at and above/below the site of fixation, respectively.

      Diagnostic tools or outcome measures

      The principal biomechanical “tool” still used by most chiropractors is palpation. As such, there has been a continued investigation into factors that change what is felt during palpation. Humans are relatively good at discriminating different magnitudes of stiffness for purely “elastic” materials.
      • Nicholson L
      • Adams R
      • Maher C
      Magnitude estimation of manually assessed elastic stiffness: stability of the exponent.
      However, the human spine responds as a viscoelastic system, in which the speed of force application changes the apparent stiffness. Nicholson et al
      • Nicholson LL
      • Adams RD
      • Maher CG
      Manual discrimination capability when only viscosity is varied in viscoelastic stiffness stimuli.
      have shown that the relatively poor ability of clinicians to accurately estimate spine stiffness magnitudes is likely due to a 50% poorer ability to discriminate viscous components of viscoelastic systems. Latimer et al
      • Latimer J
      • Lee M
      • Adams RD
      The effects of high and low loading forces on measured values of lumbar stiffness.
      found that therapists used different forces to discern spine stiffness and, hence, had different internal perceptual scales. By training therapists to use a calibrated stiffness instrument, discrimination of PA stiffness in the spine can be done with relatively high interexaminer reliability.
      • Chiradejnant A
      • Maher CG
      • Latimer J
      Objective manual assessment of lumbar posteroanterior stiffness is now possible.
      Furthermore, objective instruments have been developed that can reliably measure PA spine stiffness.
      • Shirley D
      • Ellis E
      • Lee M
      The response of posteroanterior lumbar stiffness to repeated loading.
      Perhaps, the most important aspect of using palpation to detect subluxations (ie, a “manipulable lesion”) is standardization of training.
      • Marcotte J
      • Normand MC
      • Black P
      The kinematics of motion palpation and its effect on the reliability for cervical spine rotation.
      When examiners are trained in a standardized fashion, they are able to obtain relatively high interexaminer reliability (κ = 0.68) for detecting cervical fixations.
      Stiffness of the spine is influenced by many factors. If the ribcage is constrained, then the stiffness measured at T12-L4 can be significantly increased.
      • Chansirinukor W
      • Lee M
      • Latimer J
      Contribution of ribcage movement to thoracolumbar posteroanterior stiffness.
      Change in orientation of an applied load to the spinous process can have small yet significant changes in objectively measured stiffness.
      • Allison GT
      • Edmondston SJ
      • Roe CP
      • Reid SE
      • Toy DA
      • Lundgren HE
      Influence of load orientation on the posteroanterior stiffness of the lumbar spine.
      Furthermore, because the spine is a viscoelastic system, there will be a preconditioning effect when applying loads, such that after preconditioning the spine with standard mobilization SM, there will be no measurable change in stiffness.
      • Allison G
      • Edmonston S
      • Kiviniemi K
      • Lanigan H
      • Simonsen AV
      • Walcher S
      Influence of standardized mobilization on the posteroanterior stiffness of the lumbar spine in asymptomatic subjects.
      There has also begun to be a growing appreciation for the natural (and normal) variability in spine stiffness as assessed by standard ROM tests during a physical examination. Christensen and Nilsson
      • Christensen HW
      • Nilsson N
      Natural variation of cervical range of motion: a one-way repeated-measures design.
      found that in asymptomatic volunteers during a 3-week period, there was an intrinsic variability in ROM of the cervical spine of ± 20°, ± 14°, and ± 12° for flexion/extension, lateral bending, and rotation, respectively. In contrast, repositioning the head to the neutral position, which is related to proprioception, is done with relatively high fidelity over the same period.
      • Christensen HW
      • Nilsson N
      The ability to reproduce the neutral zero position of the head.
      Asymptomatic volunteers were able to reachieve the neutral zero position of their heads with a mean difference of 2.7°, 1.0°, and 0.7° for the sagittal, horizontal, and frontal planes, respectively.
      Using a case study approach, Lehman and McGill
      • Lehman GJ
      • McGill SM
      The influence of a chiropractic manipulation on lumbar kinematics and electromyography during simple and complex tasks: a case study.
      observed that a single HVLA SM session in the lumbar spine caused notable changes in biomechanical factors associated with a complex task (ie, a golf swing in an experienced golfer who had chronic low back pain). In addition to changes in vertebral kinematics, they observed decreased electromyographic (EMG) responses of the associated lumbar muscles. In a subsequent study, Lehman and McGill
      • Lehman GJ
      • McGill SM
      Spinal manipulation causes variable spine kinematic and trunk muscle electromyographic responses.
      found that lumbar HVLA SM in patients with low back pain resulted in variable changes in lumbar ROM and associated muscle EMG. The largest changes were associated with patients with the greatest reported pain. In a review of the available literature. Lehman
      • Lehman GJ
      Biomechanical assessments of lumbar spinal function. How low back pain sufferers differ from normals. Implications for outcome measures research. Part I: kinematic assessments of lumbar function.
      reported that, currently, the best way to discriminate between normal and low back patient groups was using biomechanical tests that assessed “higher-order kinematics during complex movement tasks.” Simpler end ROM tests had poor predictive ability.
      Another commonly performed clinical test is measuring leg lengths, especially in the prone position. Using a special designed table to minimize friction and allow independent loading of each leg, Jansen and Cooperstein
      • Jansen RD
      • Cooperstein R
      Measurement of soft tissue strain in response to consecutively increased compressive and distractive loads on a friction-based test bed.
      determined that the prone leg length test was reliable for detecting non–weight-bearing asymmetry in leg lengths. Nguyen et al
      • Nguyen HT
      • Resnick DN
      • Caldwell SG
      • Elston EW
      • Bishop BB
      • Steinhouser JB
      Interexaminer reliability of activator methods' relative leg-length evaluation in the prone extended position.
      found that there was reasonable concordance (κ = 0.6) in determining whether a short leg was present using the Activator protocol. Cooperstein et al
      • Cooperstein R
      • Morschhauser E
      • Lisi A
      • Nick TG
      Validity of compressive leg checking in measuring artificial leg-length inequality.
      found that it was possible to detect a leg length difference of 1.9 mm but recommended that only differences of greater than 3.7 mm should have confidence associated with them.

      Mathematical and Computational Models

      One of the signs of maturity of any field is the ability to produce predictive models. In spine biomechanics, most models are computationally based and either use finite element approaches
      • Goel VK
      • Clausen JD
      Prediction of load sharing among spinal components of a C5-C6 motion segment using the finite element approach.
      or optimization with minimization of an objective function. Analytical approaches have also been performed, which include a linear elastic model of a lumbar motion segment.
      • Gudavalli MR
      • Triano JJ
      An analytical model of lumbar motion segment in flexion.
      This model successfully predicted loads born by various ligaments under physiologic loads. Solinger
      • Solinger AB
      Theory of small vertebral motions: an analytical model compared to data.
      created a model that predicted the dynamic response of L2-L3 to impulsive loads on the order of those used in VHVLA SM. Using a lumped parameter approach, Keller and Colloca
      • Keller TS
      • Colloca CJ
      A rigid body model of the dynamic posteroanterior motion response of the human lumbar spine.
      created an analytical model that predicted the frequency dependent response of the human lumbar spine to PA forces applied to the spinous processes, as is done during low velocity and low amplitude (ie, mobilization), HVLA, and VHVLA (ie, Activator). An alternative approach was adopted by Dulhunty
      • Dulhunty J
      A simplified conceptual model of the human cervical spine for evaluating force transmission in upright static posture.
      who modeled force transmission in the cervical spine to predict whether parallel forces or concurrent forces are the optimization function. A relatively new approach in spine modeling, especially in the lumbar spine, is to incorporate what are called “follower loads” for muscles. The issue is that the ex vivo (cadaveric) intact lumbar spine will buckle under compressive loads of ∼100 N, whereas in vivo, the lumbar spine easily supports compressive loads of ∼1000 N (ie, 10 times greater). Patwardhan et al
      • Patwardhan AG
      • Meade KP
      • Lee B
      A frontal plane model of the lumbar spine subjected to a follower load: implications for the role of muscles.
      found that by modeling muscle activation so that their loads followed the tangent of the lumbar lordosis, their model would approximate the in vivo condition.
      A couple of new comprehensive models have been advanced to explain how the spine becomes subluxated in the first place and how SM can restore it to “normal.” Triano
      • Triano J
      The mechanics of spinal manipulation.
      • Triano JJ
      Theoretical basis for spinal manipulation.
      has advocated a mechanical model based on the concept of intersegmental buckling, which was based on original observations by Wilder et al
      • Wilder DG
      • Pope MH
      • Frymoyer JW
      The biomechanics of lumbar disc herniation and the effect of overload and instability.
      • Wilder DG
      • Pope MH
      • Seroussi RE
      The balance point of the intervertebral motion segment: an experimental study.
      and fluoroscopic recordings of a buckling event in a weightlifter by Cholewicki et al
      • Cholewicki J
      • McGill SM
      • Norman RW
      Lumbar spine loads during the lifting of extremely heavy weights.
      and Cholewicki and McGill.
      • Cholewicki J
      • McGill SM
      Lumbar posterior ligament involvement during extremely heavy lifts estimated from fluoroscopic measurements.
      Essentially, this model proposes that there is a balance point between each pair of vertebrae that under certain loading conditions can suddenly shift, which then results in increased tissue strain of associated soft tissues (eg, facet joint capsule). The increased tissue strain can result in small tears and associated biologic inflammatory response. Evans et al
      • Evans JM
      • Hill CR
      • Leach RA
      • Collins DL
      The minimum energy hypothesis: a unified model of fixation resolution.
      have proposed an optimization model where the spine system is biased toward minimizing the mechanical energy associated with loading the spine. Their model is described for the case of linear elasticity, although they claim it is also apropos of nonlinear elasticity. As with any theory (or model), the value of these new theories is really found in their predictive ability and how well their predictions are validated by experimental data. So far, neither of these theories has been tested to any degree.

      Instrumented Manipulation

      Passive devices have been used for many decades to treat patients with back disorders. Recently, a simple distraction device, Rola Stretcher (Unique Relief, Inc, Davenport, Iowa), designed to be used at home without supervision, was tested to determine whether it showed any lengthening of the spine subsequent to its use. Devocht et al
      • Devocht JW
      • Pope MH
      • Magnusson M
      • Spratt KF
      Biomechanic evaluation of the Rola Stretcher as a passive distraction device.
      tested 12 asymptomatic adults and found a significant increase in sitting height after 10 minutes of lying supine on the device. They concluded that it at least temporarily lengthened the spine, presumably by increasing the intervertebral disk height.
      In addition to the activator adjusting tool, which has had increasing amounts of scientific study,
      • Keller TS
      • Colloca CJ
      • Fuhr AW
      Validation of the force and frequency characteristics of the activator adjusting instrument: effectiveness as a mechanical impedance measurement tool.
      • Keller TS
      • Colloca CJ
      • Fuhr AW
      In vivo transient vibration assessment of the normal human thoracolumbar spine.
      • Keller TS
      • Colloca CJ
      • Gunzburg R
      Neuromechanical characterization of in vivo lumbar spinal manipulation. I. Part, Vertebral motion.
      • Colloca CJ
      • Keller TS
      • Gunzburg R
      Biomechanical and neurophysiological responses to spinal manipulation in patients with lumbar radiculopathy.
      the PulStar computer-assisted, differential compliance spinal instrument has been developed, and a few studies on it have appeared.
      • Leach RA
      Differential compliance instrument in the treatment of infantile colic: a report of two cases.
      • Leach RA
      • Parker PL
      • Veal PS
      PulStar differential compliance spinal instrument: a randomized interexaminer and intraexaminer reliability study.
      This latter device also applies an impulse load (up to ∼150 N), although the duration of the impulse has not been characterized in articles available in the indexed peer-reviewed literature. The device also incorporates a sensor to measure the compliance of the material that it loads, and hence, the compliance of the paraspinal region can be assessed as well as loaded with the same device. A case study has reported that the instrument was used to treat the spines of infants having colic.
      • Leach RA
      • Parker PL
      • Veal PS
      PulStar differential compliance spinal instrument: a randomized interexaminer and intraexaminer reliability study.

      Recommendations and Action Steps

      • 1.
        Determine (quantify) the biomechanical basis of the subluxation.
        • a.
          Determine the parameters that dictate whether a given vertebra should be manipulated.
        • b.
          Determine the parameters that will guide the optimal approach to administering the manipulation.
      • 2.
        Determine the effects of manipulation on tissues of the spine.
        • a.
          Which ligaments (including facet joint capsule) sustain the largest strains due to SM
        • b.
          The influence of the vector direction of a given type of SM on ligament strains
        • c.
          Measure the effects of SM on change in tissue characteristics (eg, ligament modulus of elasticity) and cellular response to SM.
      • 3.
        Quantify the biomechanical safety of SM in fracture, disk lesions, ligament strains, muscle, and tendon strains.
      • 4.
        Develop comprehensive models of the spine that predict how it responds to physiologic and SM loads.
      • 5.
        Determine the biomechanical parameters of SM that dominate the neurophysiologic beneficial effects of SM.

      Somatic Nervous System

      Knowledge of and research directions for understanding the effects of chiropractic spinal adjusting on the somatic nervous system needs, as its basis, an understanding of neurophysiology as it relates to structure and function of the vertebral column. Thus, 2 areas are presented in this portion of the white paper. The first area beginning immediately below represents a substantial portion of our knowledge base for understanding the neurophysiologic properties of paraspinal tissues. The second area beginning with the section on Effects of SMs on Muscle and Muscle Spindles reviews how neural elements of the vertebral column and their organization are affected by SM. Information is included that predates the 1997 white paper when it was not included in that article.

      Experimental Models to Study Somatic Inputs from the Paraspinal Tissues

      Since publication of the original white paper, 2 experimental animal models have been developed that facilitate study of the relationship between spinal biomechanics and neurophysiology in general and of SM specifically: a cervical spine model developed by Bolton and Holland
      • Bolton PS
      • Holland CT
      An in vivo method for studying afferent fibre activity from cervical paravertebral tissue during vertebral motion in anaesthetised cats.
      and a lumbar spine model developed by Pickar.
      • Pickar JG
      An in vivo preparation for investigating neural responses to controlled loading of a lumbar vertebra in the anesthetized cat.
      Additional animal models also relevant to chiropractic spinal adjusting are presented in the section on Animal Models later in this paper. The experimental preparations enable application of controlled mechanical loads to individual vertebra and, at the same time, provide access to the dorsal roots for recording neural activity from paraspinal tissues affected by the mechanical load. The discharge properties of primary afferents with receptive fields in paraspinal tissues and the effects of these sensory inputs on somatomotor, somatovisceral, and central neural processing can be determined. The preparations use a servo-driven motor to control the displacement of or force applied to the spinous process.
      Recently, a large animal model (goat) has been used to determine how strains in the facet capsule affect neural input from the capsule.
      • Lu Y
      • Chen C
      • Kallakuri S
      • Patwardhan A
      • Cavanaugh JM
      Development of an in vivo method to investigate biomechanical and neurophysiological properties of spine facet joint capsules.
      This model needs additional work to determine whether the capsule is sufficiently preloaded to enable accurate determination of strain and to confirm that identified neurons can be distinguished in the multiunit recordings.
      The preparations described in this section provide the opportunity to conduct neurophysiologic studies not possible in humans. With information obtained from these animal models, hypotheses can be formulated and then tested noninvasively in humans.

      Sensory Input from Group I and II Afferents (Proprioceptive Afferents)

      Group I and II afferents are primary sensory neurons that convey information to the central nervous system from muscle spindles, Golgi tendon organs, and other low threshold mechanoreceptors such as Ruffini endings and Pacinian corpuscles. These afferents conduct action potentials rapidly (>35 m/s) due to their large diameters and heavy myelination.
      The structure and function of muscle spindles in the vertebral column have some unique aspects compared with those in the appendicular skeleton. Studies in animal models have described muscle spindles in the hind limb as single receptors located both deep in the muscle belly and close to the musculotendinous junction.
      • Matthews PBC
      Muscle spindles and their motor control.
      • Matthews PBC
      Mammalian muscle receptors and their central actions.
      • Hunt CC
      Mammalian muscle spindle: peripheral mechanisms.
      • Boyd IA
      The isolated mammalian muscle spindle.
      Spindle densities range from 5 to 45 spindles per gram of hindlimb muscle weight.
      • Chin NK
      • Cope M
      • Pang M
      Number and distribution of spindle capsules in seven hindlimb muscles of the cat.
      In the cervical spine of the human
      • Cooper S
      • Daniel PM
      Human muscle spindles.
      and cat,
      • Richmond FJR
      • Abrahams VC
      Morphology and distribution of muscle spindles in dorsal muscles of cat neck.
      • Bakker DA
      • Richmond FJR
      Muscle spindle complexes in muscles around upper cervical vertebrae in the cat.
      however, muscle spindles are rarely seen as single entities, and their densities are greater than in peripheral musculature. In the cat, Richmond and Abrahams
      • Richmond FJR
      • Abrahams VC
      Morphology and distribution of muscle spindles in dorsal muscles of cat neck.
      describe cervical spindle complexes wherein 2 to 6 spindles are in close contact with each other or share capsules and/or intrafusal fibers. Spindle density can be 2 to 8 times higher (47-107 spindles per gram) in superficial cervical muscles
      • Richmond FJR
      • Abrahams VC
      Morphology and distribution of muscle spindles in dorsal muscles of cat neck.
      and 10 to 25 times higher (137-460 spindles per gram) in deep cervical muscles
      • Bakker DA
      • Richmond FJR
      Muscle spindle complexes in muscles around upper cervical vertebrae in the cat.
      than in hindlimb muscles. These differences in spindle densities between axial neck muscles and appendicular muscles appears similar in the humans.
      • Boyd-Clark LC
      • Briggs CA
      • Galea MP
      Muscle spindle distribution, morphology, and density in longus colli and multifidus muscles of the cervical spine.
      In the lumbar spine of the cat, Carlson
      • Carlson H
      Histochemical fiber composition of lumbar back muscles in the cat.
      identified muscle spindles in the longissimus, iliocostalis, sacrocaudalis, intertransversarii, multifidus, and interspinalis muscles, but quantification and morphological description of the spindles were not performed. Similarly, muscle spindles have been identified in the medial, intermediate, and lateral portions of the lumbar erector spinae in the human fetus.
      • Amonoo-Kuofi HS
      The number and distribution of muscle spindles in human intrinsic postvertebral muscles.
      Carlson
      • Carlson H
      Histochemical fiber composition of lumbar back muscles in the cat.
      also noted that spindle density appeared higher in the central compared with peripheral portions of the longissimus. The high spindle density in the cervical and lumbar muscles is consistent with the high percentage of slow twitch fibers found in muscles of these 2 regions.
      • Richmond FJR
      • Abrahams VC
      Morphology and distribution of muscle spindles in dorsal muscles of cat neck.
      • Carlson H
      Histochemical fiber composition of lumbar back muscles in the cat.
      The reflex organization of sensory input from paraspinal muscles spindles also has some unique aspects compared with that of the appendicular skeleton. A well-recognized concept related to the cat hindlimb is that the monosynaptic stretch reflex is elicited by excitation of muscle spindles. Afferents from each muscle spindle synapse upon α-motoneurons to that same muscle (homonymous α-motoneurons).
      • Liddell EGT
      • Sherrington CS
      Reflexes in response to stretch (myotatic reflexes).
      • Lloyd DPC
      Conduction and synaptic transmission of the reflex response to stretch in spinal cats.
      • Hunt CC
      The effect of stretch receptors from muscle on the discharge of motoneurones.
      This stretch reflex arc uses a single excitatory synapse to homonymous α-motoneurons.
      • Lloyd DPC
      Conduction and synaptic transmission of the reflex response to stretch in spinal cats.
      • Lloyd DPC
      Integrative pattern of excitation and inhibition in two-neuron reflex arc.
      The afferent arm of the reflex is comprised primarily of group Ia and possibly group II afferents.
      • Hunt CC
      The effect of stretch receptors from muscle on the discharge of motoneurones.
      • Kirkwood PA
      • Sear TA
      Monosynaptic excitation of motoneurons from secondary endings of muscle spindles.
      Each group Ia afferent from a given hindlimb muscle makes functional, monosynaptic connections with 50% to 100% of the homonymous α-motoneurons.
      • Mendell LM
      • Henneman E
      Terminals of single Ia fibers: location, density, and distribution within a pool of 300 homonymous motoneurons.
      • Clamann HP
      • Henneman E
      • Luscher HR
      • Mathis J
      Structural and topographical influences on functional connectivity in spinal monosynaptic reflex arcs in the cat.
      Thus, stimulation of a group Ia afferent from a specific hindlimb muscle evokes a monosynaptic excitatory postsynaptic potential in all α-motoneurons to the same muscle.
      • Henneman E
      • Mendell LM
      Functional organization of motoneuron pool and its inputs.
      • Scott JG
      • Mendell LM
      Individual EPSPs produced by single triceps surae Ia afferent fibers in homonymous and heteronymous motoneurons.
      In contrast, in the cervical spine, the monosynaptic reflex connections to homonymous α-motoneurons are weaker. Excitatory postsynaptic potentials are smaller in amplitude, and group Ia afferents make functional connections with only 10% of the homonymous α-motoneurons.
      • Brink EE
      • Jinnai K
      • Ilson WVJ
      Pattern of segmental monosynaptic input to cat dorsal neck motoneurons.
      • Keirstead SA
      • Rose PK
      Monosynaptic projections of single muscle spindle afferents to neck motoneurons in the cat.
      This probably contributes to the absence or weakness of monosynaptic reflexes in cervical muscle.
      • Abrahams VC
      • Richmond F
      • Rose PK
      Absence of monosynaptic reflex in dorsal neck muscles of the cat.
      In the lumbar spine of the cat, stretch reflexes can be elicited from the longissimus muscle but not from the iliocostalis muscle. Conduction delays suggest that the reflex arc is not monosynaptic
      • Carlson H
      Observations on stretch reflexes in lumbar back muscles of the cat.
      unlike that in the hindlimb.
      • Lloyd DPC
      Conduction and synaptic transmission of the reflex response to stretch in spinal cats.
      • Lloyd DPC
      Integrative pattern of excitation and inhibition in two-neuron reflex arc.
      The presence of monosynaptic stretch reflexes from the deeper lumbar muscles has not been determined. In humans, indirect evidence for the presence of muscle spindles and muscle spindle reflexes in lumbar paraspinal muscles was obtained by measuring evoked cerebral potentials in response to vibration of the lumbar paraspinal muscles,
      • Zhu Y
      • Haldeman S
      • Starr A
      • Seffinger MA
      • Su S
      Paraspinal muscle evoked cerebral potentials in patients with unilateral low back pain.
      which relatively selectively stimulates muscle spindles.
      • Burke D
      • Hagbarth K-E
      • Wallin BG
      • Lofstedt L
      Muscle spindle activity induced by vibration in man: implications for the tonic stretch reflex.
      Muscle spindles, along with Golgi tendon organs, comprise a proprioceptive feedback system, which contributes to the sense of movement and position.
      • Goodwin GM
      • Matthews PBC
      • McCloskey DI
      The contribution of muscle afferents to kinaesthesia shown by vibration induced illusions of movement and by the effects of paralysing joint afferents.
      • Burgess PR
      • Wei JY
      Signaling of kinesthetic information by peripheral sensory receptors.
      • McCloskey DI
      Kinesthetic sensibility.
      Abnormal sensory input from muscle spindles elicits limb lengthening illusions.
      • Goodwin GM
      • Matthews PBC
      • McCloskey DI
      The contribution of muscle afferents to kinaesthesia shown by vibration induced illusions of movement and by the effects of paralysing joint afferents.
      • Goodwin GM
      • McCloskey DI
      • Matthews PBC
      Proprioceptive illusions induced by muscle vibration: contribution by muscle spindles to perception?.
      When a vibrating mechanical stimulus (100 Hz) is applied to the Achilles tendon of a person standing erect with eyes closed, primary endings in the muscle spindle are excited. Because they monitor change in muscle length, the increased neural discharge signals to the central nervous system that the calf muscles are stretched or lengthened more than they actually are. Spindles increase their static firing rate by ∼4 to 5 Hz per millimeter of muscle lengthening.
      • Matthews PBC
      Mammalian muscle receptors and their central actions.
      Because calf muscles normally lengthen as the body leans forward, the proprioceptive feedback error arising from the vibratory stimulus elicits a postural compensation in the form of backward sway. This movement compensates for the illusory forward flexion at the ankle. Recently, Wise et al
      • Wise AK
      • Gregory JE
      • Proske U
      The detection of movements of the human forearm during and after co-contractions of muscles acting at the elbow joint.
      showed that spindles in muscles surrounding the elbow are sufficiently sensitive to signal 0.05° to 0.15° changes in elbow rotation. Thus, it seems reasonable to suppose that paravertebral muscle spindles can signal extremely small positional changes or movement of the vertebra to which their parent muscle is attached and, thus, contribute to control of intervertebral motions that might minimize or prevent noxious spinal loading.
      Recent findings in humans suggest that proprioceptive input from paravertebral muscle spindles is important for normal reflex activity and repositioning of the lumbar spine. For example, tapping the erector spinae muscles normally elicits short latency paravertebral EMG activity. However, vibration of the lumbar paravertebral muscles, which increases background spindle discharge, inhibits this reflex response.
      • Dimitrijevic MR
      • Gregoric MR
      • Sherwood AM
      • Spencer WA
      Reflex responses of paraspinal muscles to tapping.
      Additional evidence indicates that proprioceptive input from spindles in the lumbar paravertebral muscles is necessary to accurately position the pelvis and lumbosacral spine. Although healthy individuals can accurately reposition their lumbosacral spine, their repositioning ability is impaired when muscle spindle discharge is increased by applying vibration to the lumbar paravertebral muscles.
      • Brumagne S
      • Lysens R
      • Swinnen S
      • Verschueren S
      Effect of paraspinal muscle vibration on position sense of the lumbosacral spine.
      • Brumagne S
      • Cordo P
      • Lysens R
      • Verschueren S
      • Swinnen S
      The role of paraspinal muscle spindles in lumbosacral position sense in individuals with and without low back pain.
      The correct position is consistently undershot because of the misperception of vertebral position. Interestingly, lumbosacral repositioning ability is impaired in individuals with a history of low back pain but is improved in the presence of vibration, unlike normal individuals.
      • Brumagne S
      • Cordo P
      • Lysens R
      • Verschueren S
      • Swinnen S
      The role of paraspinal muscle spindles in lumbosacral position sense in individuals with and without low back pain.
      Proprioceptive input can alter muscle force directly via its effect on α-motoneuron excitability and indirectly via its effect on the excitability of segmental and suprasegmental interneurons. Even small changes in paraspinal muscle forces are thought to have a large impact on a motion segment's biomechanical behavior and stability. For example, in vitro experiments accompanied by a modeling approach, which incorporated graded activity of 1 lumbar paraspinal muscle,
      • Panjabi MM
      • Kuniyoshi A
      • Duranceau J
      • Oxland T
      Spinal stability and intersegmental muscle forces: a biomechanical model.
      showed an increase in vertebral stabilization as determined by decreases in the intersegmental neutral zone and ROM. Similarly, very small increases in lumbar paraspinal muscle activity at L2-L4 (1-3% of maximal voluntary contraction) were sufficient to restore segmental stability to the lumbar spine even under strenuous loading conditions.
      • Cholewicki J
      • McGill SM
      Mechanical stability of the in vivo lumbar spine: implications for injury and chronic low back pain.
      More complex modeling that incorporates force vectors from 5 paraspinal muscles suggests that neuromuscular
      • Wilke HJ
      • Wolf S
      • Claes LE
      • Arand M
      • Weisand A
      Stability increase of the lumbar spine with different muscle groups: a biomechanical in vitro study.
      mechanisms controlling multifidus muscle activity alone could functionally impact a lumbar motion segment especially during flexion-extension and axial rotation.
      A recent study suggests the presence of a previously unrecognized phenomenon in the lumbar multifidus and longissimus muscles that could affect proprioceptive mechanisms controlling paraspinal muscle function.
      • Pickar JG
      • Wheeler JD
      Response of muscle proprioceptors to spinal manipulative-like loads in the anesthetized cat.
      Changes in intersegmental positions in the lumbar spine that elongated the paraspinal muscles for 10 seconds desensitized paraspinal muscle spindles to subsequent vertebral movement when compared with intersegmental positions that shortened the paraspinal muscles. The findings suggested that either voluntary static postures or involuntary intervertebral positions, which are maintained for short durations, could elicit proprioceptive feedback errors and alter paraspinal muscle force. The spine may be particularly susceptible to this phenomenon because intersegmental positions are not under voluntary control, and a vertebra's spatial position is not uniquely determined at low loads.
      • Panjabi MM
      The stabilizing system of the spine. I.I. Part, Neutral zone and instability hypothesis.

      Sensory Input from Group III and IV Afferents

      Group III and IV afferents from deep tissue (labeled as A-δ and C-fibers, respectively, when from skin) are primary sensory neurons with mechanically, chemically, or thermally sensitive receptive endings. Some endings are sensitive to only a single modality; others are polymodal. Group III and IV mechanoreceptive endings can have high or low thresholds to mechanical stimuli. Those group III and IV endings that respond in a graded fashion to any stimulus that threatens or actually inflicts injury are called “nociceptors.” Group III and IV afferents conduct their action potentials slowly (≤30 m/s) because of their small diameters and light myelination (group III) or lack of myelination (group IV).
      Deep tissues of the low back are innervated by afferent endings responsive to both mechanical and chemical stimuli.
      • Cavanaugh JM
      • El-Bohy A
      • Hardy WN
      • Getchell TV
      • Getchell ML
      • King AI
      Sensory innervation of soft tissues of the lumbar spine in the rat.
      • Ozaktay AC
      • Yamashita T
      • Cavanaugh JM
      • King AI
      Fine nerve fibers and endings in the fibrous capsule of the lumbar facet joint.
      • Avramov AI
      • Cavanaugh JM
      • Getchell TV
      • King AI
      The effects of controlled mechanical loading on group II, III, and IV afferent units from the lumbar facet joint and surrounding tissue.
      • Yamashita T
      • Cavanaugh JM
      • Ozaktay AC
      • Avramov AI
      • Getchell TV
      • King AI
      Effect of substance P on mechanosensitive units of tissues around and in the lumbar facet joint.
      • Ozaktay AC
      • Cavanaugh JM
      • Blagoev DC
      • Getchell TV
      • King AI
      Effects of a carrageenan-induced inflammation in rabbit lumbar facet joint capsule and adjacent tissues.
      • Pickar JG
      • McLain RF
      Responses of mechanosensitive afferents to manipulation of the lumbar facet in the cat.
      • Bove GM
      • Light AR
      Unmyelinated nociceptors of rat paraspinal tissues.
      For example, Cavanaugh et al
      • Cavanaugh JM
      • El-Bohy A
      • Hardy WN
      • Getchell TV
      • Getchell ML
      • King AI
      Sensory innervation of soft tissues of the lumbar spine in the rat.
      recorded multiunit activity from group III and IV afferents from the medial branch of the dorsal rami from deep connective tissue after removing lower back muscles in the rat. Gentle probing of the facet capsule, as well as forceful pulling on the supraspinous ligament, elicited a slowly adapting discharge from these afferent nerves. In a systematic study of 57 unmyelinated afferents from the tail and lumbar region of the rat, Bove and Light
      • Bove GM
      • Light AR
      Unmyelinated nociceptors of rat paraspinal tissues.
      found mechanonociceptive endings in muscle bellies, tendon, subcutaneous tissue, and neurovascular bundles. Up to a third of the afferents had receptive endings in more than 1 tissue. No receptive fields were found in the facet joint capsule. Pickar and McLain
      • Pickar JG
      • McLain RF
      Responses of mechanosensitive afferents to manipulation of the lumbar facet in the cat.
      recorded single-unit activity from group III and group IV afferents in the intact lumbar spine of cats during movement of the L5-6 facet joint. Most afferents, including 7 with receptive fields in or near the facet joint capsule, responded in a graded fashion to the direction of a nonnoxious load applied to the joint. Yamashita et al
      • Yamashita T
      • Cavanaugh JM
      • Ozaktay AC
      • Avramov AI
      • Getchell TV
      • King AI
      Effect of substance P on mechanosensitive units of tissues around and in the lumbar facet joint.
      found that only 20% of group III afferents in and around the lumbar facet joint had high mechanical thresholds (>8.5 g), as determined with von Frey–like hairs. This latter finding contrasts with afferents studied in the cervical spine where almost all group III afferents studied had high mechanical thresholds.
      • Richmond FJR
      • Abrahams VC
      Physiological properties of muscle spindles in dorsal neck muscles of the cat.
      In addition, Bolton and Holland
      • Bolton PS
      • Holland CT
      An in vivo method for studying afferent fibre activity from cervical paravertebral tissue during vertebral motion in anaesthetised cats.
      found silent afferents innervating the cervical facet joints, which were only activated by firm, potentially noxious prodding of their receptive fields.
      Most unmyelinated mechanonociceptive afferents are also sensitive to chemical stimulation by capsaicin, but only 50% were sensitive to the inflammatory agent bradykinin.
      • Bove GM
      • Light AR
      Unmyelinated nociceptors of rat paraspinal tissues.
      Group III and IV receptive endings in and around the lumbar facet joint can be both activated and sensitized by chemical stimuli. Substance P increases their resting discharge by 80% and decreases their von Frey thresholds by −30%.
      • Yamashita T
      • Cavanaugh JM
      • Ozaktay AC
      • Avramov AI
      • Getchell TV
      • King AI
      Effect of substance P on mechanosensitive units of tissues around and in the lumbar facet joint.
      Similarly, carrageenan-induced inflammation increases the resting discharge of group III, group IV, and some group II afferents innervating the lumbar muscles and facet joints and sensitizes their receptive endings to mechanical stimuli.
      • Ozaktay AC
      • Cavanaugh JM
      • Blagoev DC
      • Getchell TV
      • King AI
      Effects of a carrageenan-induced inflammation in rabbit lumbar facet joint capsule and adjacent tissues.
      The inflammation also activates previously silent group III and IV afferents.
      • Ozaktay AC
      • Cavanaugh JM
      • Blagoev DC
      • Getchell TV
      • King AI
      Effects of a carrageenan-induced inflammation in rabbit lumbar facet joint capsule and adjacent tissues.
      In the cervical spine, group III afferents with a resting discharge were insensitive to the inflammatory mediator bradykinin,
      • Richmond FJR
      • Abrahams VC
      Physiological properties of muscle spindles in dorsal neck muscles of the cat.
      but previously silent small-diameter afferents were activated by bradykinin.
      • Bolton PS
      • Holland CT
      An in vivo method for studying afferent fibre activity from cervical paravertebral tissue during vertebral motion in anaesthetised cats.
      These neural responses to inflammation likely underlie the findings that mustard oil induced inflammation elicits muscle activity in the neck. Mustard oil intensely activates high-threshold C-fibers (group IV afferents).
      • Woolf CJ
      • Wall PD
      Relative effectiveness of C primary afferent fibers of different origins in evoking a prolonged facilitation of the flexor reflex in the rat.
      When very small volumes (20 μL) were injected into deep cervical paraspinal tissues, EMG activity was increased in a wide variety of upper cervical muscles including digastric, masseter, trapezius, and rectus capitis posterior.
      • Hu JW
      • Yu X-M
      • Vernon H
      • Sessle BJ
      Excitatory effects on neck and jaw muscle activity of inflammatory irritant applied to cervical paraspinal tissues.
      Because the volume was small and its spread to the neighboring tissues was limited, the effects were likely mediated by a reflex. The large number of muscles affected by inflammation of cervical paraspinal muscles may relate to the hyperconvergence, described by Gillette et al
      • Gillette RG
      • Kramis RC
      • Roberts WJ
      Characterization of spinal somatosensory neurons having receptive fields in lumbar tissues of cats.
      (see next paragraph), and to the communication between segmental paraspinal tissues via intersegmental connections within the spinal cord, reported by the laboratory of Pickar.
      • Kang YM
      • Choi WS
      • Pickar JG
      Electrophysiologic evidence for an intersegmental reflex pathway between lumbar paraspinal tissues.
      Dorsal horn neurons in the spinal cord with receptive fields in the lumbar paraspinal tissues, including paraspinal muscles and facet joints, receive more convergent input from group III and IV afferents than is true for dorsal horn neurons with receptive fields in the limbs.
      • Gillette RG
      • Kramis RC
      • Roberts WJ
      Characterization of spinal somatosensory neurons having receptive fields in lumbar tissues of cats.
      In these electrophysiologic studies, Gillette et al
      • Gillette RG
      • Kramis RC
      • Roberts WJ
      Characterization of spinal somatosensory neurons having receptive fields in lumbar tissues of cats.
      found that wide dynamic range and nociceptive specific neurons in the superficial dorsal horn of the L4-5 spinal segments shared receptive fields with deep and superficial tissues of the lumbar spine, the hip, and proximal leg. This type of input was termed hyperconvergent. Axonal tracing studies revealed that small diameter primary afferents from multifidus muscle and facet joints produce substantial bilateral labeling in laminae I, II, and III, as well as in the deeper laminae V-VIII and X.
      • Gillette RG
      • Kramis RC
      • Roberts WJ
      Spinal projections of cat primary afferent fibers innervating lumbar facet joints and multifidus muscle.
      Many of these laminae are involved in nociceptive processing and also project to autonomic centers.

      Axons Inside or Outside the IVF

      Adhesions, fixations, or discal herniation may produce an ectopic source of neural activity. Bove et al
      • Bove GM
      • Ransil BJ
      • Lin HC
      • Leem JG
      Inflammation induces ectopic mechanical sensitivity in axons of nociceptors innervating deep tissues.
      inflamed the axons of mechanically sensitive group II, III, and IV afferents that innervate both superficial and deep structures. The inflammation led to increased spontaneous activity and/or increased mechanical sensitivity of only the group III and IV axons innervating deeper structures.
      Increasing evidence shows that the mechanical and chemical consequences of a herniated disk can affect neural tissue within the IVF. Dorsal roots and dorsal root ganglia (DRG) are more susceptible to the effects of mechanical compression than are axons of peripheral nerves because impaired or altered function is produced at substantially lower pressures.
      • Rydevik BL
      The effects of compression on the physiology of nerve roots.
      • Howe JF
      • Loeser JD
      • Calvin WH
      Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression.
      Applying as little as 10 mm Hg of pressure to the dorsal root reduces by 20% to 30% the nutritional transport to peripheral axons.
      • Olmarker K
      • Rydevik B
      • Hansson T
      • Holm S
      Compression-induced changes of the nutritional supply to the porcine cauda equina.
      Recently, a mean pressure of 53 mm Hg (range, 7-256 mm Hg) was measured between a herniated disk and the nerve root in 34 humans undergoing surgery for lumbar disk herniation.
      • Takahashi K
      • Shima I
      • Porter RW
      Nerve root pressure in lumbar disc herniation.
      Song et al
      • Song XJ
      • Xu DS
      • Vizcarra C
      • Rupert RL
      Onset and recovery of hyperalgesia and hyperexcitability of sensory neurons following intervertebral foramen volume reduction and restoration.
      inserted small pins into the IVF to model a space-reducing lesion in an animal model. Although pressures in the IVF were not measured, this lesion produced mechanical hyperalgesia in the hindlimb and increased the excitability of dorsal root ganglion cells.
      The application of nucleus pulposus to a lumbar nerve root increases spontaneous nerve activity and increases the mechanical sensitivity of dorsal root ganglion cells.
      • Takebayashi T
      • Cavanaugh JM
      • Cuneyt Ozaktay A
      • Kallakuri S
      • Chen C
      Effect of nucleus pulposus on the neural activity of dorsal root ganglion.
      In addition, nucleus pulposus applied to a lumbar nerve root produces mechanical hyperalgesia,
      • Kawakami M
      • Tamaki T
      • Hayashi N
      • Hashizume H
      • Matsumoto T
      • Minamide A
      • et al.
      Mechanical compression of the lumber nerve root alters pain-related behaviors induced by the nucleus pulposus in the rat.
      causes swelling in and decreases blood flow to the DRG, and decreases blood flow to the lower leg.
      • Yabuki S
      • Igarashi T
      • Kikuchi S
      Application of nucleus pulposus to the nerve root simultaneously reduces blood flow in dorsal root ganglion and corresponding hindpaw in the rat.
      Moderate doses of phospholipase A2, an inflammatory mediator associated with disk herniation, also increases the mechanical sensitivity of dorsal roots, produces long-lasting discharges, and increases the discharge of previously silent dorsal root ganglion cells.
      • Chen C
      • Cavanaugh JM
      • Ozaktay AC
      • Kallakuri S
      • King AI
      Effects of phospholipase A2 on lumbar nerve root structure and function.
      • Ozaktay AC
      • Kallakuri S
      • Cavanaugh JM
      Phospholipase A2 sensitivity of the dorsal root and dorsal root ganglion.
      As mentioned in the previous section, extruded nucleus pulposus contains high levels of TNF-α, and 2 studies have shown that the inhibition of TNF-α by a monoclonal antibody (Remicade) is successful in alleviating sciatica.
      • Korhonen T
      • Karppinen J
      • Malmivaara A
      • Autio R
      • Niinimki J
      • Paimela L
      • et al.
      Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.
      • Karppinen J
      • Korhonen T
      • Malmivaara A
      • Paimela L
      • Kyllönen E
      • Lindgren K-A
      • et al.
      Tumor necrosis factor–α monoclonal anti-body, infliximab, used to manage severe sciatica.
      It should be noted that several case studies
      • Triano J
      The mechanics of spinal manipulation.
      • Floman Y
      • Liram N
      • Gilai AN
      Spinal manipulation results in immediate H-reflex changes in patients with unilateral disc herniation.
      • Stern PJ
      • Côte P
      • Cassidy JD
      A series of consecutive cases of low back pain with radiating leg pain treated by chiropractors.
      and randomized clinical studies
      • Nwuga VC
      Relative therapeutic efficacy of vertebral manipulation and conventional treatment in back pain management.
      • Burton AK
      • Tillotson KM
      • Cleary J
      Single-blind randomised controlled trial of chemonucleolysis and manipulation in the treatment of symptomatic lumbar disc herniation.
      show that patients with herniated intervertebral disk, who received SM, gained clinical improvement.

      Effects of SMs on Muscle and Muscle Spindles

      Spinal manipulation induces somatomotor changes, that is, changes in muscle activity, apparently because of sensory input from the somatic nervous system. In asymptomatic patients, Herzog's group
      • Herzog W
      • Scheele D
      • Conway PJ
      Electromyographic responses of back and limb muscles associated with spinal manipulative therapy.
      • Suter E
      • Herzog W
      • Conway PJ
      • Zhang YT
      Reflex response associated with manipulative treatment of the thoracic spine.
      showed that PA spinal manipulative treatments applied to the cervical, thoracic, lumbar, and sacroiliac regions increased paraspinal EMG activity in a pattern related to the region of the spine that was manipulated. The EMG response latencies occur within 50 to 200 milliseconds after initiation of the manipulative thrust. Similarly, SM using an Activator-adjusting instrument applied to a transverse process elicited paraspinal EMG activity at the same segmental level but within 2 to 3 milliseconds.
      • Fuhr AW
      • Smith DC
      Accuracy of piezoelectric accelerometers measuring displacement of a spinal adjusting instrument.
      This is surprisingly fast for a reflex response. Colloca and Keller