Decreased μ-opioid receptor signalling and a reduction in calcium current density in sensory neurons from chronically morphine-treated mice

Emma E. Johnson, Billy Chieng, Ian Napier, Mark Connor*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Sensory neurons are a major site of opioid analgesic action, but the effect of chronic morphine treatment (CMT) on μ-opioid receptor function in these cells is unknown. We examined μ-opioid receptor modulation of calcium channel currents (I Ca) in small trigeminal ganglion (TG) neurons from mice chronically treated with morphine and measured changes in μ-opioid receptor mRNA levels in whole TG. Mice were injected subcutaneously with 300 mg kg -1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). CMT mice had a significantly reduced response to the acute antinociceptive effects of 30 mg kg -1 morphine compared with controls (P = 0.035). Morphine inhibited I Ca in neurons from CMT (EC 50 300 nM) and vehicle (EC 50 300 nM) mice with similar potency, but morphine's maximum effect was reduced from 36% inhibition in vehicle to 17% in CMT (P < 0.05). Similar results were observed for the selective μ-opioid agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin (DAMGO). Inhibition of I Ca by the GABA B agonist baclofen was unaffected by CMT. In neurons from CMT mice, there were significant reductions in P/Q-type (P = 0.007) and L-type (P = 0.002) I Ca density. μ-Opioid receptor mRNA levels were not altered by CMT. These data demonstrate that CMT produces a significant reduction of the effectiveness of μ-opioid agonists to inhibit I Ca in TG sensory neurons, accompanied by a reduction in I Ca density. Thus, adaptations in sensory neurons may mediate some of the tolerance to the antinociceptive effects of morphine that develop during systemic administration.

Original languageEnglish
Pages (from-to)947-955
Number of pages9
JournalBritish Journal of Pharmacology
Volume148
Issue number7
DOIs
Publication statusPublished - 12 Aug 2006
Externally publishedYes

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