The Effect of Site and Type of Nerve Injury on Spinal Glial Activation and Neuropathic Pain Behavior

A number of rat peripheral neuropathy models have been developed to simulate human neuropathic pain conditions. The current study sought to determine the relative importance of site versus type of peripheral nerve injury in eliciting mechanical allodynia and spinal glial responses. Rats received one of seven different surgical treatments at the L5 spinal level: spinal nerve cryoneurolysis, spinal nerve tight ligation, dorsal root cryoneurolysis, dorsal root tight ligation, dorsal root transection, ventral root tight ligation, or laminectomy/dural incision sham. Foot-lift response frequency to mechanical stimulation of the ipsilateral hindpaw was assessed postlesion on days 1, 3, 5, and 7. L5 spinal cords were retrieved for immunohistochemical analysis of microglial (OX-42) and astrocytic (anti-glial fibrillary acidic protein) responses. Both types of spinal nerve lesion, freeze and tight ligation, produced rapid and profound mechanical allodynia with intense glial responses. Dorsal root lesions also resulted in intense mechanical allodynia; however, glial responses were almost exclusively astrocytic. Ventral root tight ligation and sham provoked no marked behavioral changes and only sporadic glial responses. Direct dorsal horn communication with the dorsal root ganglion was not a crucial factor in the development of mechanical allodynia, since decentralization of the L5 DRG by complete L5 dorsal root lesion produced profound mechanical sensitization. Conversely, microglial activation responses appear to be dependent upon dorsal root ganglion-mediated signals and, contrary to behavioral responses, were robust only when the lesion was made peripheral to the cell body. Astrocytic activation was always observed following axonal injury and reliably coexisted with behavioral responses.