Co-expression of μ and δ opioid receptors by mouse colonic nociceptors

BACKGROUND AND PURPOSE To better understand opioid signalling in visceral nociceptors, we examined the expression and selective activation of mu and delta opioid receptors by dorsal root ganglia (DRG) neurons innervating the mouse colon. EXPERIMENTAL APPROACH DRG neurons projecting to the colon were identified by retrograde tracing. delta receptor-GFP reporter mice, in situ hybridization, single-cell RT-PCR and mu receptor-specific antibodies were used to characterize expression of mu and delta receptors. Voltage-gated Ca2+ currents and neuronal excitability were recorded in small diameter nociceptive neurons (capacitance <30 pF) by patch clamp and ex vivo single-unit afferent recordings were obtained from the colon. KEY RESULTS In situ hybridization of oprm1 expression in Fast Blue-labelled DRG neurons was observed in 61% of neurons. mu and delta receptors were expressed by 36-46% of colon DRG neurons, and co-expressed by similar to 25% of neurons. mu and delta receptor agonists inhibited Ca2+ currents in DRG, effects blocked by opioid antagonists. One or both agonists inhibited action potential firing by colonic afferent endings. Incubation of neurons with supernatants from inflamed colon segments inhibited Ca2+ currents and neuronal excitability. Antagonists of mu , but not delta receptors, inhibited the effects of these supernatant on Ca2+ currents, whereas both antagonists inhibited their actions on neuronal excitability. CONCLUSIONS AND IMPLICATIONS A significant number of small diameter colonic nociceptors co-express mu and delta receptors and are inhibited by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at mu or delta receptors, or their heterodimers may be effective in treating visceral pain.