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Peripheral antinociception induced by δ-opioid receptors activation, but not μ- or κ-, is mediated by Ca²⁺-activated

Daniela da Fonseca Pacheco1, Cinthia Mara da Fonseca Pacheco, Igor Dimitri Gama Duarte

  • 1Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, CEP: 31.270.100, Belo Horizonte, Brazil.

European Journal of Pharmacology
|December 3, 2011
PubMed

Insights

Calcium-activated chloride channels (CaCCs) are involved in peripheral pain relief from delta-opioid receptor activation. However, CaCCs do not play a role in pain relief mediated by mu- or kappa-opioid receptors or the nitric oxide pathway.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Research

Background:

  • Opioid receptor activation involves the L-arginine/NO/cGMP pathway and ion channels.
  • Peripheral antinociception mechanisms following opioid exposure require further elucidation.
  • The potential role of Ca(2+)-activated Cl(-) channels (CaCCs) in opioid-induced analgesia is unexplored.

Purpose of the Study:

  • To investigate the involvement of CaCCs in peripheral antinociception induced by mu-, delta-, and kappa-opioid receptor activation.
  • To determine if CaCCs mediate pain relief through the L-arginine/NO/cGMP pathway.

Main Methods:

  • Hyperalgesia was induced using prostaglandin E(2) (PGE(2)) in an animal model.
  • Nociceptive thresholds were measured after administration of opioid receptor agonists (morphine, SNC80, bremazocine) and CaCCs blockers (niflumic acid, NPPB).
  • The effects of nitric oxide (NO) donor (SNP) and cGMP analog (db-cGMP) on antinociception were assessed in the presence of CaCCs blockers.

Main Results:

  • CaCCs blockers partially reversed the antinociception induced by the delta-opioid receptor agonist SNC80 in a dose-dependent manner.
  • CaCCs blockers did not affect the antinociceptive effects of the mu-opioid receptor agonist morphine or the kappa-opioid receptor agonist bremazocine.
  • Niflumic acid did not inhibit antinociception induced by the NO donor SNP or db-cGMP, indicating no link between CaCCs and the L-arginine/NO/cGMP pathway.

Conclusions:

  • CaCCs are involved in peripheral antinociception specifically mediated by delta-opioid receptor activation.
  • CaCCs activation is not implicated in the peripheral antinociceptive effects of mu- and kappa-opioid receptor agonists.
  • The L-arginine/NO/cGMP pathway is not linked to CaCCs in the context of opioid-induced peripheral antinociception.

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