TY - JOUR
T1 - Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn
AU - Bardoni, Rita
AU - Tawfik, Vivianne L.
AU - Wang, Dong
AU - François, Amaury
AU - Solorzano, Carlos
AU - Shuster, Scott A.
AU - Choudhury, Papiya
AU - Betelli, Chiara
AU - Cassidy, Colleen
AU - Smith, Kristen
AU - deNooij, Joriene C.
AU - Mennicken, Françoise
AU - O'Donnell, Dajan
AU - Kieffer, Brigitte L.
AU - Woodbury, C. Jeffrey
AU - Basbaum, Allan I.
AU - MacDermott, Amy B.
AU - Scherrer, Grégory
PY - 2014/3/19
Y1 - 2014/3/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896300470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896300470&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2014.01.044
DO - 10.1016/j.neuron.2014.01.044
M3 - Article
C2 - 24583022
AN - SCOPUS:84896300470
SN - 0896-6273
VL - 81
SP - 1312
EP - 1327
JO - Neuron
JF - Neuron
IS - 6
ER -