Zerumbone-induced antinociception: involvement of the L-arginine-nitric oxide-cGMP -PKC-K+ ATP channel pathways

Basic Clin Pharmacol Toxicol. 2011 Mar;108(3):155-62. doi: 10.1111/j.1742-7843.2010.00635.x. Epub 2010 Oct 18.

Abstract

This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Arginine / metabolism*
  • Behavior, Animal / drug effects
  • Cyclic GMP / antagonists & inhibitors
  • Cyclic GMP / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • KATP Channels / antagonists & inhibitors
  • KATP Channels / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Pain Measurement
  • Potassium Channel Blockers / pharmacology
  • Protein Kinase C / metabolism*
  • Receptor, Bradykinin B2 / agonists
  • Receptor, Bradykinin B2 / metabolism
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes / therapeutic use*
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / metabolism
  • Time Factors

Substances

  • Analgesics
  • KATP Channels
  • Potassium Channel Blockers
  • Receptor, Bradykinin B2
  • Sesquiterpenes
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Nitric Oxide
  • zerumbone
  • Arginine
  • Protein Kinase C
  • Cyclic GMP