delta-opioid receptors and nitric oxide mediate the analgesic effect of Crotalus durissus terrificus snake venom

Eur J Pharmacol. 2000 Mar 10;391(1-2):55-62. doi: 10.1016/s0014-2999(99)00934-6.

Abstract

The antinociceptive effect of Crotalus durissus terrificus venom was investigated in a model of inflammatory hyperalgesia induced by carrageenin. The rat paw pressure test was applied before and 3 h after the intraplantar (i.pl.) injection of carrageenin. The venom administered per os before and 1 or 2 h after carrageenin blocked hyperalgesia. When carrageenin was injected in both hind paws and naloxone into one hind paw, antinociception was abolished only in the paw injected with naloxone. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) and nor-binaltorphimine, antagonists of micro- and kappa-opioid receptors, respectively, did not alter the effect of the venom. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), an antagonist of delta-opioid receptors, antagonised this effect. Prolonged administration of the venom did not induce tolerance to this antinociceptive effect. N(G)-methyl-L-arginine (L-NMMA) and methylene blue, inhibitors of nitric oxide synthase and soluble guanylate cyclase, respectively, injected i.pl., antagonised antinociception. These data indicate that both delta-opioid receptors and nitric oxide participate in the mediation of the peripheral antinociceptive effect of C. durissus terrificus venom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Arginine / metabolism
  • Carrageenan
  • Crotalid Venoms / pharmacology*
  • Cyclic GMP / metabolism
  • Edema / chemically induced
  • Edema / prevention & control
  • Enzyme Inhibitors / pharmacology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / prevention & control
  • Male
  • Methylene Blue / pharmacology
  • Motor Activity / drug effects
  • Narcotic Antagonists / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / drug effects
  • Receptors, Opioid, delta / physiology*
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, mu / antagonists & inhibitors
  • omega-N-Methylarginine / pharmacology

Substances

  • Analgesics, Non-Narcotic
  • Crotalid Venoms
  • Enzyme Inhibitors
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • omega-N-Methylarginine
  • Nitric Oxide
  • Carrageenan
  • Arginine
  • Nitric Oxide Synthase
  • Cyclic GMP
  • Methylene Blue