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Inflammation enhances peripheral μ-opioid receptor-mediated analgesia, but not μ-opioid receptor transcription in dorsal root ganglia

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Abstract

μ-Opioid receptor agonist [d-Ala2,NMe-Phe4,Gly5-ol]enkephalin (DAMGO)-induced peripheral analgesic effects occur early in hindpaws inoculated with Freund's complete adjuvant and increase in parallel to the development of inflammatory signs. Antagonism of these effects by β-funaltrexamine, an irreversible μ-opioid receptor antagonist, suggests that the effective number of peripheral opioid receptors does not increase during early stages, but does so at later stages of the inflammation. As determined by a ribonuclease protection assay, μ-opioid receptor mRNA in dorsal root ganglia is abundant in untreated animals, but does not significantly increase following inflammation. Thus, peripheral analgesic efficacy of DAMGO is not correlated with transcription or number of μ-opioid receptors at early inflammatory stages. At later stages, however, the number of peripheral μ-opioid receptors appears to increase and may enhance opioid efficacy.

Keywords

Antinociception
μ-Opioid receptor
Dorsal root ganglion
Primary afferent neuron
Ribonuclease protection assay
β-Funaltrexamine

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