PRIMING ENHANCES ENDOTOXIN-INDUCED THERMAL HYPERALGESIA AND MECHANICAL ALLODYNIA IN RATS

Central inflammation is an integral component and contributor of the p athology of many debilitating diseases and has been shown to produce s pontaneous pain and hyperalgesia. Recently, administration of lipopoly saccharide (LPS) into the lateral ventricle of rats was shown to elici t both thermal hyperalgesia and tactile allodynia [K. Walker, A. Dray, M. Perkins, Hyperalgesia in rats following intracerebroventricular ad ministration of endotoxin: effect of bradykinin B-1 and B-2 receptor a ntagonist treatment, Pain 65 (1996) 211-219]. In this study, we have r eplicated the LPS model with some adaptations and correlated the nocic eptive behaviors with an increased expression of activated macrophages in the central nervous system. We also examined the effects of primin g on LPS-induced decreases in thermal nociceptive thresholds and mecha nical response thresholds following either central or peripheral admin istration, Intracerebroventricular (i.c.v.) administration of LPS (0.2 mu g/rat) did not alter either thermal (hot plate) or mechanical (von Frey filaments) thresholds compared to baseline values in the first f ew hours after injection. However, priming rats by pretreating with i. c.v, LPS (0.2 mu g) 24 h prior to testing with i.c.v. LPS (0.2 mu g) p roduced significant mechanical allodynia and thermal hyperalgesia. The mechanical allodynia had an onset of 80 min after injection and a dur ation of 5 h. A similar time course was observed for thermal hyperalge sia, although its expression was less pronounced. Immunohistochemical studies indicated an increased expression of activated macrophages in the brain parenchyma of primed rats but not in unprimed rats. Intraper itoneal (i.p., 2 mg/kg) administration of LPS had no significant effec t on either thermal or mechanical thresholds in the first few hours af ter injection; however, priming rats via i.p. (0.2 mg/kg) or i.c.v, (0 .2 mu g) LPS produced a reduction in both thermal nociceptive threshol ds and mechanical response thresholds in rats given a subsequent i.p. injection of LPS. This study demonstrates that priming is an effective protocol for the induction of central inflammation and increases the duration of these behaviors after i.c.v. administration. (C) 1998 Publ ished by Elsevier Science B.V. All rights reserved.