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Neuron. 2014 Mar 19;81(6):1312-1327. doi: 10.1016/j.neuron.2014.01.044. Epub 2014 Feb 27.

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

Author information

1
Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41100 Modena, Italy.
2
Department of Anesthesiology, Perioperative and Pain Medicine, Department of Molecular and Cellular Physiology, Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA.
3
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
4
Department of Physiology and Cellular Biophysics, Department of Neuroscience, Columbia University, New York, NY 10032, USA.
5
Graduate Program in Neuroscience, University of Wyoming, Laramie, WY 82071, USA; Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA.
6
Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
7
AstraZeneca R&D Montreal, Department of Translational Science, Montreal, QC H4S 1Z9, Canada.
8
Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR7104 CNRS/Université de Strasbourg, U964 INSERM, 67400 Illkirch, France.
9
Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA.
10
Department of Anesthesiology, Perioperative and Pain Medicine, Department of Molecular and Cellular Physiology, Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA. Electronic address: gs25@stanford.edu.

Erratum in

  • Neuron. 2014 Mar 19;81(6):1443.

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.

PMID:
24583022
PMCID:
PMC4072501
DOI:
10.1016/j.neuron.2014.01.044
[Indexed for MEDLINE]
Free PMC Article

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