Role of capsaicin-sensitive afferents in fever and cytokine responses during systemic and local inflammation in rats

Objective: Peripheral afferents play an important role in fever. In the pre sent study, we investigated the role of capsaicin-sensitive afferents in fe ver and cytokine responses during systemic (induced by intraperitoneal lipo polysaccharide, LPS) and local (induced by injection of Freund's incomplete adjuvant, FIA, into the paw) inflammation. Methods: Fevers in rats (8-10 w eeks of age) whose capsaicin-sensitive afferents were depleted by neonatal capsaicin (50 mg/kg) treatment were compared to those of rats treated as ne onates with vehicle. To investigate a possible involvement of cytokines, pl asma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were me asured during LPS- and FIA-induced fever in rats after capsaicin-induced de sensitization. Body temperature was measured by biotelemetry. IL-6 and TNF bioactivities in plasma were determined using bioassays. Results: The initi al but not the late phase of LIPS (50 mug/kg)-induced fever was markedly hi gher (similar to1.0 degreesC) in rats whose capsaicin-sensitive neurons wer e destroyed by neonatal capsaicin treatment. Capsaicin-induced desensitizat ion also resulted in significantly higher plasma levels of IL-6 and TNF 1 b ut not 4 h after LPS challenge. In contrast, the day after injection with F IA (0.1 ml), rats treated with capsaicin had significantly lower body tempe ratures compared with vehicle-treated animals. No differences were found in plasma levels of IL-6 and TNF between capsaicin- and vehicle-treated anima ls in response to FIA. Conclusions: These data indicate that the role of ca psaicin-sensitive afferents in fever depends on the type of inflammatory re sponse. During systemic inflammation, capsaicin-sensitive afferents may be involved in modulating fever by regulating the levels of pyrogenic cytokine s. During local inflammation, the late phase of fever is partially mediated via capsaicin-sensitive afferents. Copyright (C) 2001 S. Karger AG, Basel.