ANTIINFLAMMATORY INTERLEUKIN-10 THERAPY IN CCI NEUROPATHY DECREASES THERMAL HYPERALGESIA, MACROPHAGE RECRUITMENT, AND ENDONEURIAL TNF-ALPHAEXPRESSION

The chronic constriction injury model of mononeuropathy is a direct, p artial nerve injury yielding thermal hyperalgesia. The inflammation th at results from this injury is believed to contribute importantly to b oth the neuropathological and behavioral sequelae. This study involved administering a single dose (250 ng) of interleukin-10 (IL-IO), an en dogenous anti-inflammatory peptide, at the site and time of a chronic constriction injury (CCI) lesion to determine if IL-10 administration could attenuate the inflammatory response of the nerve to CCI and resu lting thermal hyperalgesia. In IL-10-treated animals, thermal hyperalg esia was significantly reduced following CCI (days 3, 5 and 9). Histol ogical sections from the peripheral nerve injury site of those animals had decreased cell profiles immunoreactive for ED-I, a marker of recr uited macrophages, at both times studied (2 and 5 days post-CCT). IL-1 0 treatment also decreased cell profiles immunoreactive for the pro-in flammatory cytokine tumor necrosis factor alpha (TNF-alpha) at day 2, but not day 5. Qualitative light microscopic assessment of neuropathol ogy at the lesion site did not suggest substantial differences between IL-IO and vehicle-treated sections. The authors propose that initial production of TNF-alpha and perhaps other proinflammatory cytokines at the peripheral nerve lesion site importantly influences the long-term behavioral outcome of nerve injury, and that IL-10 therapy may accomp lish this by downregulating the inflammatory response of the nerve to injury. (C) 1998 International Association for the Study of Pain. Publ ished by Elsevier Science B.V.