Opioids inhibit purinergic nociceptors in the sensory neurons and fibres of rat via a G protein-dependent mechanism

I. Chizhmakov, Y. Yudin, N. Mamenko, I. Prudnikov, Z. Tamarova, O. Krishtal

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

We have found that opioid and P2X receptors are functionally coupled in the sensory nerve fibres and neurons of rat. When examined in the skin-nerve preparation, the ATP-evoked discharges of nerve fibres belonging to n. saphenous were inhibited by various opiates in a naloxone-dependent manner. The functional coupling between opioid and purinergic receptors was studied in the neuronal cell bodies isolated from dorsal root and nodose ganglia. Both fast (mediated by P2X3 receptors) and slow (P2X2/3 heteromeric receptors) responses of sensory neurons to ATP were inhibited by opioids. The inhibition of slow responses developed in a characteristic biphasic manner: an initial short phase of potentiation (lasting for 300-400 s) was followed by long-lasting inhibition of the response (for about 50% when saturated). Both phases of the response were initiated by the application of the highly selective ligand for μ-receptors, endomorphin 1 (30 nM). Intracellular GTPγS caused a partial inhibition of the ATP responses and opioids were not effective against the residual response. Intracellular GDP eliminated the effects of opioids, while pertussis toxin (PTX) abolished only the inhibition phase. Thus, P2X receptors in the sensory neurons are affected by opioids via multiple G protein-dependent pathways.

Original languageEnglish (US)
Pages (from-to)639-647
Number of pages9
JournalNeuropharmacology
Volume48
Issue number5
DOIs
StatePublished - Apr 2005
Externally publishedYes

Keywords

  • G proteins
  • Nociceptors
  • Opioid receptors
  • P2X receptors
  • Sensory neurons

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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