Onset and recovery of hyperalgesia and hyperexcitability of sensory neurons following intervertebral foramen volume reduction and restoration☆

Abstract 

Objective

To investigate the relationships between L4 and L5 intervertebral foramen (IVF) stenosis (IVFS), as well as the restoration and onset and recovery of behavioral hyperalgesia and alterations in primary sensory neuron excitability.

Methods

IVFS was produced by surgically implanting stainless steel rods unilaterally into the intervertebral foramen at L4 and L5. The insertion of a stainless steel rod in the IVF caused IVF volume reduction, which mimics IVFS. The rods were kept for up to 14 weeks in 16 rats and 2 to 4 weeks in another 32 rats. Rod withdrawal was expected to restore the IVF volume. The rods were withdrawn in 20 rats on the 7th day and in another 20 rats on the 14th day, postoperatively. Two additional groups of control rats received no surgery or sham operation. Behavioral hyperalgesia was evidenced by the significantly decreased threshold and shortened latency of foot withdrawal to mechanical and thermal stimulation of the plantar surface. Electrophysiological intracellular recordings were obtained in vitro from L4 and/or L5 dorsal root ganglia (DRG).

Results

The IVFS rats exhibited a rapid-onset (≤1 day), long-lasting (10-11 weeks), mechanical, and thermal hyperalgesia. DRG neurons in each category, large-sized, medium-sized, and small-sized, from IVFS rats were more excitable than those from control rats, evaluated by the significantly decreased threshold current and action potential threshold and increased number of discharges evoked by depolarizing current and incidence of spontaneous activity. IVF volume restoration significantly reduced behavioral hyperalgesia and the increased excitability of DRG neurons. In contrast, sham surgery produced no behavioral or electrophysiological changes in the ganglion neurons.

Conclusion

The present study demonstrates that hyperalgesia and hyperexcitability of the primary sensory neurons can be induced following the IVF volume reduction produced by insertion of a stainless steel rod and mostly relieved by the rod withdrawal. The recovery of excitability of DRG cells to normal levels is associated with the abatement of hyperalgesia. These results support the hypothesis that increased excitability of DRG neurons is associated with the generation and maintenance of hyperalgesia and suggest that relief of the IVF stenosis, which could compress all of the normal constituents within the IVF (ie, DRG, nerve root, blood and lymph vessels, adipose, etc.), may help to alleviate chronic pain in humans.

Keywords:  Dorsal Root Ganglion, Intervertebral Foramen, Stenosis, Hyperalgesia, Hyperexcitability