PAINFUL MONONEUROPATHY IN C57BL WLD MICE WITH DELAYED WALLERIAN DEGENERATION - DIFFERENTIAL-EFFECTS OF CYTOKINE PRODUCTION AND NERVE REGENERATION ON THERMAL AND MECHANICAL HYPERSENSITIVITY/

Wallerian degeneration with macrophage influx and production of proinf lammatory cytokines is a critical factor in the development of hyperal gesia in animal models of neuropathic pain. We hypothesized that in th e mouse strain with delayed Wallerian degeneration, the C57BL/Wld mous e, the temporal course of mechanical allodynia and thermal hyperalgesi a as well as the temporal profile of cytokine expression after nerve i njury would differ from normal mice. Here we used the model of chronic constriction injury of the sciatic nerve (CCI) to study the correlati on of pain related behavior with peripheral nerve de-and regeneration and concomitant cytokine production. Indeed, after CCI, C57BL/Wld mice showed markedly reduced thermal hyperalgesia compared to normal C57BL /6 mice, temporally related to the delayed recruitment of hematogeneou s macrophages to the injured nerve. Endoneurial tumor necrosis factor- alpha (TNF)-like immunoreactivity increased rapidly in normal mice but did so with a delayed time course in C57BL/Wld mice. In addition, the duration of mechanical allodynia was significantly prolonged in C57BL /Wld mice as compared to C57BL/6 mice, in accordance with the delay in regeneration of sensory nerve fibers in these mice. These results sug gest that macrophage invasion and production of TNF may influence the development of thermal hyperalgesia and that regenerative activity is linked to mechanical allodynia in peripheral mononeuropathy. (C) 1998 Elsevier Science B.V.