Role of calcium channels in the spinal transmission of nociceptive information from the mesentery

Gyöngyi Horváth, Birgit Brodacz, Ulrike Holzer-Petsche

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Opioids, α2-adrenoceptor agonists and blockers of voltage-gated calcium channels (VGCCs) have been attributed antinociceptive activity in various experimental set-ups. The present study tested the ability of morphine, clonidine and drugs acting at various VGCCs to inhibit the transmission of noxious stimuli from the mesentery at the level of the spinal cord. In rats under barbiturate anaesthesia traction of 20 g was applied to a bundle of mesenteric blood vessels. This caused immediate transient changes of mean arterial pressure that were taken as indication of nociception. Similar reflexes were elicited by applying 0.6% acetic acid to the same bundle of vessels. The reflexes were dose-dependently reduced by intrathecal administration of morphine or clonidine, but were left unaltered by intrathecal administration of verapamil, Bay-K 8644 or ω-conotoxin MVIIA. Neither verapamil nor Bay-K 8644 influenced clonidine-induced analgesia. Conotoxin markedly enhanced the effectiveness of all doses of clonidine against both types of mesenteric stimuli. Verapamil, Bay-K 8644, as well as conotoxin reduced the ability of morphine to inhibit mechanically evoked reflexes, while there was no statistically significant effect in chemonociception. These data suggest that, at the spinal level, both morphine and clonidine are effective drugs to decrease the cardiovascular changes caused by acute mesenteric pain. In the dorsal spinal cord neither L-type nor N-type VGCCs are responsible on their own for the transmission of noxious stimuli from the mesentery. Inhibition of N-type channels markedly augments the action of clonidine, whereas blocking either VGCC seems to inhibit antinociceptive mechanisms induced by morphine. It is suggested that in patients the combined administration of clonidine with ω-conotoxin MVIIA might lead to effective pain control with reduced side effects.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalPain
Volume93
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • Clonidine
  • Morphine
  • Spinal cord
  • Verapamil
  • Visceral nociception
  • ω-Conotoxin MVIIA

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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