Crotalus durissus terrificus VENOM INDUCES ANTINOCICEPTION IN A RAT MODEL OF CANCER PAIN. INHIBITION OF TUMOR GROWTH BY CROTOXIN

¹Brigatte, P; ¹Sampaio, S.C., ¹Gutierrez, V.P.; ²Curi, R.; ³Rangel-Santos, A.C.; ⁴Guerra, J.L.; ¹Chacur, M. ¹Cury, Y.

Laboratories of ¹Pathophysiology, and ³Immunopathology, Butantan Institute, SP, ²Departament of Physiology and Biophysics, ICB, USP, ⁴Departament of Pathology, FMVZ, USP, SP.

Crotalusdurissus terrificus venom (Cdtv) induces central and peripheral antinociceptive effect. Despite these evidences, the action of Cdtv or crotoxin (Ctx), the main venom toxin, on experimental cancer pain has not been characterised yet. The present study determined: a) whether carcinosarcoma inoculation would induce hyperalgesia (paw pressure test) and allodynia (von Frey filaments) in rats; b) the antinociceptive effect of CdtV on cancer pain; c) the involvement of opioid receptors in the antinociceptive effect; d) the action of Ctx on tumor cell growth (determined by plethysmography) and hipernociception. For induction of tumor, 1x10⁶ Walker 256 carcinoma cells were injected by intraplantar (i.pl., 100µl) route into one of the hindpaws of Wistar rats. Hyperalgesia was observed at day 5 and allodynia at day 2 after tumor cells implantation. CdtV (800-1600µg/kg, p.o) administered at day 5 produced antinociception. Naloxone (5µg/i.pl.) blocked venom-induced antinociception. Prolonged treatment (5 days) with Ctx (18µg/kg once a day) inhibited tumor growth (30%) and hipernociception. Naloxone, given at day 5, did not interfere with toxin-induced antinociception. These results demonstrate that CdtV induces antinociception on cancer pain mediated by opiod receptors. In addition, Ctx alleviate the cancer pain by suppression of the tumor growth.

Financial support: CAPES 

Correspondence to: chacur@yahoo.com