PERIPHERAL-NERVE PATHOLOGY FOLLOWING SCIATIC CRYONEUROLYSIS - RELATIONSHIP TO NEUROPATHIC BEHAVIORS IN THE RAT

Sciatic cryoneurolysis (SCN) is an experimental rat mononeuropathy mod el that produces neuropathic behavioral sequelae distinct from other n europathy models. Following SCN, there is limited autotomy peaking in severity and incidence at 7-14 days and delayed but sustained allodyni a appearing at about 21 days, with no evidence of thermal hyperalgesia . This study quantified peripheral nerve pathology at weekly intervals following SCN to determine the relationship of nerve degeneration and regeneration to the resulting abnormal behaviors. Fiber histograms ba sed on axon diameter and grid morphometry were used to quantify the pa thologic state of nerve fibers, activated phagocytic cells, vessels, a nd edema at the lesion site. Approximately 90% of the axons demonstrat ed Wallerian-like degeneration by 3 days post-SCN. At 14 days, small d iameter axons significantly increased in number from earlier times fol lowing SCN (P < 0.05) but were not significantly different from normal values. At 21 days, the number of small diameter axons was significan tly increased over both 14 days (P < 0.05) and normal values (P < 0.05 ). At 28 days, intermediate diameter axons significantly increased in number with respect to all earlier time periods (P < 0.05). These incr eases in regenerating fibers overlapped with the development of peak a utotomy at 7-14 days and the onset of allodynia after 21 days. Autotom y scores at 7 days positively correlated with grid morphometry data of regenerating axons (p = 0.7) and activated macrophages and Schwann ce lls (p = 0.8) and inversely correlated with edema (p = -0.8) using Spe arman's rank correlation analysis. These data suggest a macrophage and Schwann cell involvement in the sensitization of first- and second-or der neurons to afferent input which leads to neuropathic behaviors. Th ese results are discussed in the context of a hypothesis for the gener ation of differential neuropathic behaviors associated with the pathol ogical events of degeneration and regeneration following the chronic c onstriction injury model of neuropathic pain and SCN. (C) 1995 Academi c Press, Inc.