Inhibitory effect of anandamide on resiniferatoxin-induced sensory neuropeptide release in vivo and neuropathic hyperalgesia in the rat

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Abstract

Anandamide (AEA) is an endogenous cannabinoid ligand acting predominantly on the cannabinoid 1 (CB1) receptor, but it is also an agonist on the capsaicin VR1/TRPV1 receptor. In the present study we examined the effects of AEA and the naturally occuring cannabinoid 2 (CB 2) receptor agonist palmitylethanolamide (PEA) on basal and resiniferatoxin (RTX)-induced release of calcitonin gene-related peptide (CGRP) and somatostatin in vivo. Since these sensory neuropeptides play important role in the development of neuropathic hyperalgesia, the effect of AEA and PEA was also examined on mechanonociceptive threshold changes after partial ligation of the sciatic nerve. Neither AEA nor PEA affected basal plasma peptide concentrations, but both of them inhibited RTX-induced release. The inhibitory effect of AEA was prevented by the CB1 receptor antagonist SR141716A. AEA abolished and PEA significantly decreased neuropathic mechanical hyperalgesia 7 days after unilateral sciatic nerve ligation, which was antagonized by SR141716A and the CB2 receptor antagonist SR144528, respectively. Both SR141716A and SR144528 increased hyperalgesia, indicating that endogenous cannabinoids acting on CB1 and peripheral CB 2-like receptors play substantial role in neuropathic conditions to diminish hyperalgesia. AEA and PEA exert inhibitory effect on mechanonociceptive hyperalgesia and sensory neuropeptide release in vivo suggesting their potential therapeutical use to treat chronic neuropathic pain.

Original languageEnglish
Pages (from-to)2345-2353
Number of pages9
JournalLife sciences
Volume73
Issue number18
DOIs
Publication statusPublished - Sep 19 2003

Keywords

  • Anandamide
  • Calcitonin gene-related peptide
  • Capsaicin-sensitive nerve terminals
  • Neuropathic hyperalgesia
  • Palmitylethanolamide
  • Radioimmunoassay
  • Resiniferatoxin
  • SR141716A
  • SR144528
  • Somatostatin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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