The effect of site and type of nerve injury on spinal glial activation andneuropathic pain behavior

A number of rat peripheral neuropathy models have been developed to simulat e human neuropathic pain conditions. The current study sought to determine the relative importance of site versus type of peripheral nerve injury in e liciting mechanical allodynia and spinal glial responses. Rats received one of seven different surgical treatments at the L-5 spinal level: spinal ner ve cryoneurolysis, spinal nerve tight ligation, dorsal root cryoneurolysis, dorsal root tight ligation, dorsal root transection, ventral root tight li gation, 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. L-5 spinal cords were retrieved for immunohistochem ical analysis of microglial (OX-42) and astrocytic (anti-glial fibrillary a cidic protein) responses. Both types of spinal nerve lesion, freeze and tig ht ligation, produced rapid and profound mechanical allodynia with intense glial responses. Dorsal root lesions also resulted in intense mechanical al lodynia; however, glial responses were almost exclusively astrocytic. Ventr al root tight ligation and sham provoked no marked behavioral changes and o nly sporadic glial responses. Direct dorsal horn communication with the dor sal root ganglion was not a crucial factor in the development of mechanical allodynia, since decentralization of the L-5 DRG by complete L-5 dorsal ro ot lesion produced profound mechanical sensitization. Conversely, microglia l activation responses appear to be dependent upon dorsal root ganglion-med iated 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 behavio ral responses. (C) 1999 Academic Press.