Introduction: The symptoms of carpal tunnel syndrome include both paresthesias and pain. The source of this pain remains unclear. Recent EM data suggest that chronic nerve compression (CNC) induces aberrant axonal sprouting from pre-existing axons at the site of compression. Although these unmyelinated axons may promote regeneration, they also mediate the pain response. As it has been shown that noxious stimuli induce an up-regulation of c-fos protein within the spinal cord*, we sought to evaluate pain in a model for compression neuropathy with (1) behavioral tests including von Frey and thermal paw withdrawal analysis and (2) immunohistochemistry (IHC) against c-fos protein.

Methods: A model for CNC was created with silastic tubes (I.D. 1.3mm) placed atraumatically around the right sciatic nerve of Sprague-Dawley rats. Prior to specimen harvest, von Frey hair analysis was performed to measure paw withdrawal thresholds to evaluate mechanical allodynia. The paw withdrawal reflex of rats placed on a chilled platform was used to evaluate thermoallodynia. The L4-L6 sections of the spinal cord were subsequently removed and stained for c-fos immunoreactivity. Antibody-antigen reaction sites were visualized using DAB immunostaining.

Results: At the one month time point, IHC demonstrated that there was a significant upregulation of c-fos protein on the side of CNC injury relative to the normal contralateral extremity. The overall magnitude of c-fos expression in laminae I-IV of the spinal cord decreased between one and six months. In contrast to neuropathic pain which induces a hypersensitivity to mechanical stimulation, Von Frey data demonstrated a decrease in sensitivity to mechanical stimulation with the CNC model at the one month time-point. Thermoallodynia was uniformly absent at both one and six months after CNC.

Discussion: This is one of the first studies to rigorously evaluate the pain response with an animal model for CNC. The advent of axonal sprouting at one month post-injury corresponds to the upregulation of c-fos protein centrally. The disappearance of axonal sprouts at the six-month time-point corresponds to a reduction in c-fos expression at the same time point. Furthermore, behavioral studies demonstrated a marked absence of mechanical and thermal allodynia and confirm that the CNC model does not induce neuropathic pain. This data suggests that axonal sprouting may certainly induce a pain response without the induction of neuropathic pain. By better understanding the pathogenesis of CNC, we may begin to improve our current treatment protocols for compression neuropathies.

*Hunt SP et al. Nature 328:632-634.