Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn.

TitleDelta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn.
Publication TypeJournal Article
Year of Publication2014
AuthorsBardoni R, Tawfik VL, Wang D, François A, Solorzano C, Shuster SA, Choudhury P, Betelli C, Cassidy C, Smith K, de Nooij JC, Mennicken F, O'Donnell D, Kieffer BL, C Woodbury J, Basbaum AI, MacDermott AB, Scherrer G
JournalNeuron
Volume81
Issue6
Pagination1312-27
Date Published2014 Mar 19
ISSN1097-4199
KeywordsAnalgesics, Opioid, Animals, Calcium Channels, Ganglia, Spinal, Mechanoreceptors, Mice, Mice, Inbred C57BL, Neurons, Nociceptors, Pain, Receptors, Opioid, delta, Spinal Cord
Abstract

Cutaneous mechanosensory neurons detect mechanical stimuli that generate touch and pain sensation. Although opioids are generally associated only with the control of pain, here we report that the opioid system in fact broadly regulates cutaneous mechanosensation, including touch. This function is predominantly subserved by the delta opioid receptor (DOR), which is expressed by myelinated mechanoreceptors that form Meissner corpuscles, Merkel cell-neurite complexes, and circumferential hair follicle endings. These afferents also include a small population of CGRP-expressing myelinated nociceptors that we now identify as the somatosensory neurons that coexpress mu and delta opioid receptors. We further demonstrate that DOR activation at the central terminals of myelinated mechanoreceptors depresses synaptic input to the spinal dorsal horn, via the inhibition of voltage-gated calcium channels. Collectively our results uncover a molecular mechanism by which opioids modulate cutaneous mechanosensation and provide a rationale for targeting DOR to alleviate injury-induced mechanical hypersensitivity.

DOI10.1016/j.neuron.2014.01.044
Alternate JournalNeuron
PubMed ID24583022
PubMed Central IDPMC4072501
Grant ListDA029204 / DA / NIDA NIH HHS / United States
DA031777 / DA / NIDA NIH HHS / United States
F32 NS079066 / NS / NINDS NIH HHS / United States
K99 DA031777 / DA / NIDA NIH HHS / United States
NS029797 / NS / NINDS NIH HHS / United States
NS044094 / NS / NINDS NIH HHS / United States
R00 DA031777 / DA / NIDA NIH HHS / United States
R01 DA029204 / DA / NIDA NIH HHS / United States
R01 NS029797 / NS / NINDS NIH HHS / United States
R01 NS044094 / NS / NINDS NIH HHS / United States
R37 NS014627 / NS / NINDS NIH HHS / United States

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