Opioidergic Transmission in the Dorsal Horn

  • Juan Carlos Marvizon


The potent analgesia produced by opiate drugs is induced, at least in part, in the spinal cord. The three “classical” opioid receptors, µ, δ and κ, are found in dorsal horn neurons and primary afferent terminals. Dorsal horn neurons expressing opioid receptors are mostly excitatory, and their inhibition by opioids decreases pain intensity. In primary afferents, opioid receptors inhibit the release of the pro-nociceptive neuropeptides substance P and CGRP. The spinal cord also contains “atypical” opioid receptors: the nociceptin receptor, the opioid growth factor receptor and toll-like receptors, which modulate pain in ways still not well understood. Enkephalins and dynorphins are the main opioid peptides in the dorsal horn, and are expressed by different neuronal populations. Endorphins are not found in the dorsal horn, and recent studies question whether endomorphins are indeed endogenous. Enkephalins and dynorphins are highly susceptible to peptidase degradation, which has prompted the use of peptidase inhibitors as analgesics. Endogenous peptidase inhibitors with analgesic properties have also been found. Opioid release in the spinal cord is inhibited by several neurotransmitter receptors, including adrenergic α2C receptors, serotonin 5-HT1A receptors and NMDA receptors. Spinal opioid release appears to be driven by signals originating in both in primary afferents and supraspinally. Pain modality appears to determine whether pain induces spinal opioid release through local or supraspinal circuits. Some forms of stress-induced analgesia are also mediated by spinal opioid release. This involves a circuit originating in the dorsal raphe nucleus involved in the fear/anxiety response. Spinal opioids also mediate the analgesia induced by acupuncture.


Opioid Receptor Dorsal Horn Opioid Peptide Dorsal Raphe Nucleus Dorsal Horn Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





adrenocorticotropin hormone

BK channels

Ca2+-sensitive large conductance potassium channels


N-type voltage-gated Ca2+ channels




calcitonin gene-related peptide


central nervous system




corticotrophin-releasing factor


[D-Ala2, N-methyl-Phe4, Gly-ol5]enkephalin


δ-opioid receptor


dorsolateral funiculus


[D-penicillamine2, D- penicillamine5]enkephalin; DRN, dorsal raphe nucleus


dorsal root ganglia


G protein-coupled receptor


κ-opioid receptor


high pressure liquid chromatography


µ-opioid receptor


nucleus raphe magnus


neurokinin 1 receptor


nociceptin receptor


orphanin FQ/nociceptin


opioid growth factor


periaqueductal gray




rostral-ventral medulla


stress-induced analgesia


vesicular glutamate transporter 2


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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Center for Neurobiology of Stress, Division of Digestive Diseases, Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Veteran Affairs Greater Los Angeles Healthcare SystemLos AngelesUSA

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