Peripheral tackykinin and excitatory amino acid receptors mediate hyperalgesia induced by Phoneutria nigriventer venom

Eur J Pharmacol. 2003 Apr 25;467(1-3):111-8. doi: 10.1016/s0014-2999(03)01604-2.


The generation of hyperalgesia by Phoneutria nigriventer venom was investigated in rats using the paw pressure test, through the intraplantar injection of the venom. Hyperalgesia was significantly inhibited by N-[2-(4-chlorophenyl) ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamide (capsazepine), a vanilloid receptor antagonist, by the local administration of pGlu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Pro (spiro-gamma-lactam) Leu-Trp-NH(2) (GR82334) or of Phenyl-CO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH(2) (GR94800), inhibitors of tachykinin NK(1) and NK(2) receptors, respectively, or by the local injection of dizocilpine (MK 801), (+/-)-2-amino-5-phosphonopentanoic acid ((+/-)-AP-5), or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), antagonists of NMDA and non-NMDA excitatory amino acid receptors. The correlation between hyperalgesia and the inflammatory response induced by the venom was also investigated. The venom-induced edematogenic response was not modified by the pharmacological treatments. These results suggest that hyperalgesia induced by P. nigriventer venom is mediated by stimulation of capsaicin-sensitive neurons, with activation of peripheral tachykinin NK(1) and NK(2) receptors and of both the NMDA and AMPA receptors. Distinct mechanisms are involved in the development of hyperalgesia and edema induced by the venom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsaicin / analogs & derivatives*
  • Capsaicin / pharmacology
  • Capsaicin / therapeutic use
  • Edema / chemically induced
  • Edema / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hindlimb
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism*
  • Male
  • Pain Threshold / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / physiology
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Receptors, Neurokinin-1 / drug effects
  • Receptors, Neurokinin-1 / physiology
  • Receptors, Neurokinin-2 / drug effects
  • Receptors, Neurokinin-2 / physiology
  • Receptors, Tachykinin / antagonists & inhibitors
  • Receptors, Tachykinin / physiology*
  • Spider Venoms / toxicity*


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Receptors, Drug
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurokinin-1
  • Receptors, Neurokinin-2
  • Receptors, Tachykinin
  • Spider Venoms
  • capsazepine
  • Capsaicin