The 2005 Conference on the Biology of Manual Therapies

Neuroscience Research 

Joel Pickar, DC, PhD, presented a theoretical construct from which the neuroscience of manual therapies may be viewed. Individual presentations addressed aspects of this construct. Dr Pickar summarized possible ways manual therapies may affect the nervous system either directly or indirectly by stimulating, silencing, or normalizing the activity of primary afferents as well as higher-order neurons. The final common pathway for effects is altering physiology—muscle tone, feeling of well-being, and stress. Five presentations then described specifics.

Partap S. Khalsa, DC, PhD, described research on the encoding of mechanical stimuli. Applied forces during a spinal manipulation load a variety of innervated connective tissues: skin, muscles, tendons, ligaments, joint capsules, and intervertebral disks. At least, for high-velocity, low-amplitude manipulations, the loads applied exceed the stimulation thresholds for many types of sensory neurons. Somehow, the load is transduced into a signal that the nervous system can interpret. Studies in bacteria show that stretching the membrane of the cell itself allows a flux of ions to enter, which implies a conformational change of ion channels, a deformation, and hence, a mechanical strain in the tissue. However, over the last 2 decades, studies in mammals have consistently found the opposite. Neural response is better correlated with mechanical stress (related to force intensity) than to strain (related to deformation).

Dr Pickar presented data on the effects of nonnoxious mechanical stimuli on primary afferent neurons. Manual therapies are generally nonpainful biomechanical interventions. Understanding how nonnoxious mechanical inputs affect the activity of sensory neurons, their patterns of input, and their integration in the central nervous system will help provide an understanding of the mechanisms underlying the proposed therapeutic effects of these interventions. Manual therapies most likely take advantage of inherent signaling properties of mechanosensory afferents (group I-IV). The effectiveness of any manual therapy may arise in part from its ability to evoke neuronal activity to a magnitude or in a pattern not seen during normal activity.

James Henry, PhD, presented data on the integration of sensory information at the spinal cord level. His work has used 3 rat models of inflammatory joint disease: rheumatoid arthritis, osteoarthritis, and temporomandibular disorder. His conclusion was that the somatosensory system is plastic, and under conditions of peripheral pathology, major changes occur in spinal mechanisms of nociception.

Min Zhou, PhD, presented data from genetic and synaptic studies of sensory-related central sensitization. Spinal cord response is intensity-dependent, so a burst of activity (as in massage) likely produces a large response, including release of excitatory and inhibitory transmitters mediated through presynaptic kainate receptors. Neuronal synapses in the central nervous system are plastic, undergoing long-term changes throughout life. The recruitment of silent synapses provides a potential mechanism for long-term facilitation of sensory transmission in neuropathic pain.

Kerstin Uvnas-Moberg, PhD, discussed the role of oxytocin in antistress and well-being. Antistress effects cause dramatic fall in blood pressure (via sympathetic neurons). Data suggest that oxytocin acts like a coordinator of glucocorticoid receptor, cholinergic α2-receptor, 5-hydroxytryptamine, and opioid activity to modulate the effects of light touch on the sympathetic nervous system. In addition to touch, pressure and temperature are important for relaxing responses, all of which trigger vagal afferents, causing a pattern of antistress. Similarly, massage stimulates release of oxytocin, giving the same effects, which occur quicker when it is delivered to the front than the back side of the body.

Immune and Endocrine Systems 

Daniel Clauw, MD, presented data on the relationship between neuroendocrine factors in fibromyalgia, which is part of a large continuum of conditions involving many somatic systems with psychological and behavioral factors playing a role in some individuals. Fibromyalgia shows the prototypical mechanistic characterization of chronic pain and is thought to be caused by genetics, triggers, and mechanisms (physiologic/psychological, disordered sensory processes, etc). Chronic fatigue syndrome often co-occurs.

Jon Levine, MD, PhD, presented a neural and endocrine perspective on mechanisms by which manual therapies modulate pain. Several generalized pain syndromes (eg, fibromyalgia, irritable bowel syndrome, temporomandibular syndrome, etc) exhibit commonalities, which are more significant than their differences. They are highly dependent on sex hormones, predominantly seen after puberty, and effects are driven by stress and a variety of inputs. Sensory motor integration is important in syndromes, and manual therapies may affect those systems.

Claude Côté, PhD, presented biologic mechanisms underlying the healing phases in muscle trauma. Trauma causes an inflammatory reaction, which is resolved in 2 to 5 days. This is followed by tissue healing and regeneration (the first proliferative phase) and then remodeling and normal function. Repressing inflammation can decrease nonspecific tissue damage but can slow recovery and negatively influence the quality of muscle repair. In fact, inflammation is required to clean damaged tissue and also to initiate regeneration. Connective tissue injuries can include acute or overuse tendonitis, bursitis, capsulitis or chronic tendinosis, tennis elbow, rotator cuff syndrome, and patellar syndrome.

Firdaus Dhabhar, PhD, illuminated the enhancing vs suppressive effects of stress on the immune system. Emotions were identified as potential causes of disease some 2600 years ago, and psychoneuroimmunology is an attempt to apply principles and techniques of modern science to the age-old question of emotion-caused disease. Acute stress lasts minutes to hours; chronic stress lasts weeks to months, disturbing the diurnal rhythm. Acute stress—brief and with normal circadian rhythm—is an adaptive response that prompts increased leukocyte mobilization and protective immune response. Chronic stress or distress—prolonged and repeated—incites dysregulated immune responses and decreased leukocyte mobilization and protective immune response.

Biomechanics and Imaging 

Linda Woodhouse, PhD, stated that biologic tissue is characterized by plasticity, which may result in failure or injury. Manual therapy maximizes the difference between loads faced daily and failure. Manual therapies apply forces at varying rates and magnitudes to effect change over the cell-to-body continuum. Imaging can be done by ultrasound, magnetic resonance imaging (MRI), x-ray, computed tomography, positron emission tomography, or single photon emission computed tomography. Regardless of applied force, how we integrate responses in the periphery with responses centrally is the challenge. There are systematic responses (neurophysiological, neuroendocrine, circulatory) and regional responses (tensile strength, altered proprioceptive input, metabolic and biochemical, paracrine, genetic alterations, and blood flow). New techniques in biomechanics and imaging processes will allow us to integrate peripheral and central adaptation to the application of mechanical stimuli in humans.

John Triano, DC, PhD, discussed the biomechanical continuum that characterizes manual therapies. To quantify procedures, measurements can be taken for leg length, posture and weight-bearing symmetry, range of motion, and combined motions (static vs dynamic). Joint compliance/stiffness varies throughout the spine. However, tests for pain are more reliable than tests for compliance. Bone stress response can be measured by single photon emission spectroscopy. Other measurements are relative bone position and curvature, myoelectric signals, and helical axis of the cervical spine. Pathomechanical markers include biologic markers (eg, substance P), arterial strains, ligamentous strains, mechanoreceptor stretch, intradiscal pressure, intersegmental motion, body segment kinematics, posture/weight-bearing symmetry, gait changes, strength, blood flow, and edema. Challenges include how mechanotransduction works, load transmission pathways, relation of biomechanical parameters to outcomes, and quantification of the biomechanics for the manipulable lesion.

David Wilder, PhD, discussed the impact of ergonomics on manual therapies and a tensegrity model of the spine. Questions remain as to how and why manual therapies work and who responds best. Motion and posture are subject to external influences. Whole-body vibration causes low back problems, erector spinae muscle activity and hence posture, vibration, and disk herniation. However, not all vibration is sinusoidal. Surprise can affect response; 12% of low back problems are due to unexpected loads (back muscles tend to overcompensate with unexpected load). It is important to consider the source of the problem when determining treatment; the practitioner may have to eliminate the source in conjunction with the treatment.

Helene Langevin, MD, LAc, described her research on connective tissue mechanotransduction. A common feature of manual therapies is the application of mechanical forces to connective tissues. Immediate (viscoelastic and mechanotransduction) and delayed (remodeling) connective tissue effects of these forces may contribute to the mechanism of these therapies. Ultrasound elasticity imaging is a series of rapidly acquired ultrasound images taken during application of a mechanical stimulus. Combining cell morphometry analyses of whole tissue with in vivo elasticity imaging constitutes a potentially powerful approach to investigating mechanotransduction and tissue plasticity mechanisms of manual therapies.

Hermano Igo Krebs, PhD, discussed the implications of robotics on manual therapies. The use of therapeutic robotics has grown significantly in the last 5 years and has been transformed from “eminence-based” to evidence-based practice. Evidence shows that manipulation of an impaired limb influences recovery and that the improved outcome was sustained after 3 years.

Norman Kettner, DC, discussed the potential of functional neuroimaging techniques on manual therapy research. Critical imaging research questions include the following: What are spinal and supraspinal substrates of manual therapy? How do sensory afferents interact with the autonomic system? Does manual therapy interact with cerebral cortex? Does manual therapy interact with the pain neuromatrix and the descending inhibitory pathways? Does spinal joint immobilization and manual therapy reorganize the sensorimotor cortex? Does passive spinal movement (manual therapy) use unique neural pathways compared with active techniques? Dr Kettner reviewed advantages and disadvantages of imaging tools that could be useful in manual therapies research: positron emission tomography, magnetoencephalography, transcranial magnetic stimulation, MRI, magnetic resonance spectroscopy, and functional MRI.