PHARMACOLOGICAL MODULATION OF HYPERALGESIA INDUCED BY Phoneutria nigriventer SPIDER VENOM

ZANCHET, E.M.; CURY,Y.

Laboratory of Pathophysiology, Butantan Institute, São Paulo, Brazil.

Aim of investigation: Despite the clinical relevance of local pain observed in Phoneutria nigriventer( Pn) envenomations, no information is available concerning the algogenic activity of Pn venom. The present study was undertaken to characterize the hyperalgesic response caused by Pn venom in rats. Methods: Male Wistar rats were injected by intraplantar(i.pl.) route with Pn venom (0.01, 0.1, 1, 3 and 10 µg/paw) or saline. Pain threshold was assessed before and 1, 2, 4 and 24 hr after venom injection using the rat paw pressure test. Results: The venom caused hyperalgesia that peaked 4h (16, 42, 51, and 61% for each dose, respectively) after injection decreasing thereafter. The hyperalgesic response (1µg venom/paw) was blocked by pre-treatment with dexamethasone (1 mg/kg, s.c), GR 94800 (10µM/paw), capsazepine(120 µM/kg, i.v.), AP5 (40 pM/paw) and partially reduced by methisergide (5 mg/kg, i.p.), anti-IL-1 antibody (20 µg/kg, i.v.), 7-nitroindazol ( 50µg/paw), meloxican (200 µg/paw), GR82334 (10µM/paw), MK801 (100pM/paw) and CNQX (100 nM/paw). Treatment with promethazine (5 mg/kg, i.p.), Hoe-140 (0.6 mg/kg, i.v.), anti-TNF-a antibody (0.2 µg/paw), CGRP _8-37 (400 nM/kg, i.v) indomethacin(4 mg/kg, i.v.), zileuton(100 mg/kg, p.o.) or guanethidine(30 mg/kg, s.c., for 3 days) did not modify this phenomenon. Conclusions: The present data suggest that hyperalgesia induced by Phoneutria nigriventer venom is, at least partially, mediated by interleukin-1, prostaglandins generated by COX 2, neuronal nitric oxide, by stimulation of capsaicin sensory neurons and activation peripheral NK1 and NK2 takykinin receptors and NMDA and non-NMDA receptors.

Supported by grants from FAPESP (00/06965-8), CAPES and Fundação Butantan

CORRESPONDENCE TO:

ZANCHET, E.M., Laboratory of Pathophysiology, Butantan Institute, Avenida Vital Brasil, 1500, 05503-900, SP, Brazil, Email: emzanchet@yahoo.com.br