Co‐expression of μ and ∂ opioid receptors by mouse colonic nociceptors

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving' Copyright © 2018 The British Pharmacological Society All rights reserved. This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyBackground and Purpose To better understand opioid signaling in visceral nociceptors, we examined the expression and selective activation of mu (MOR) and delta opioid receptors (DOR) by dorsal root ganglia (DRG) neurons innervating the mouse colon. Experimental Approach DRG neurons projecting to the colon were identified by retrograde tracing. DOR‐GFP reporter mice, in situ hybridization, single‐cell RT‐PCR, and MOR‐specific antibodies were used to characterize expression of MOR and DOR. Voltage‐gated Ca2+ currents and neuronal excitability were recorded in small diameter nociceptive neurons (capacitance < 30pF) 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‐labeled DRG neurons was observed in 61% of neurons. MOR and DOR were expressed by 36‐46% of colon DRG neurons, and co‐expressed by ~25 % of neurons. MOR and DOR agonists inhibited Ca2+ currents in DRG and these effects were 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. The MOR but not the DOR antagonist, inhibited the supernatant effects 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 MOR and DOR and are inhibited by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at MOR or DOR or their heterodimers may be effective in the treatment of visceral pain