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Br J Pharmacol. 2018 Jul;175(13):2622-2634. doi: 10.1111/bph.14222. Epub 2018 May 22.

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

Author information

1
Gastrointestinal Diseases Research Unit, Queen's University, Kingston, ON, Canada.
2
Monash Institute of Pharmaceutical Sciences and Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, VIC, Australia.
3
Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia.
4
Visceral Pain Research Group, Human Physiology, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.
5
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia.
6
Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC, Australia.
7
Departments of Surgery and Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Abstract

BACKGROUND AND PURPOSE:

To better understand opioid signalling in visceral nociceptors, we examined the expression and selective activation of μ and δ 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. δ receptor-GFP reporter mice, in situ hybridization, single-cell RT-PCR and μ receptor-specific antibodies were used to characterize expression of μ and δ 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. μ and δ receptors were expressed by 36-46% of colon DRG neurons, and co-expressed by ~25% of neurons. μ and δ 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 μ, but not δ 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 μ and δ receptors and are inhibited by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at μ or δ receptors, or their heterodimers may be effective in treating visceral pain.

PMID:
29579315
PMCID:
PMC6003632
[Available on 2019-07-01]
DOI:
10.1111/bph.14222

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