Endogenous opioid peptides acting at μ-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons

D. Budai, Howard L. Fields

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Activation of neurons in the midbrain periaqueductal gray (PAG) inhibits spinal dorsal horn neurons and produces behavioral antinociception in animals and analgesia in humans. Although dorsal horn regions modulated by PAG activation contain all three opioid receptor classes (μ, δ, and κ), as well as enkephalinergic interneurons and terminal fields, descending opioid- mediated inhibition of dorsal horn neurons has not been demonstrated. We examined the contribution of dorsal horn μ-opioid receptors to the PAG- elicited descending modulation of nociceptive transmission. Single-unit extracellular recordings were made from rat sacral dorsal horn neurons activated by noxious heating of the tail. Microinjections of bicuculline (BIC) in the ventrolateral PAG led to a 60-80% decrease in the neuronal responses to heat. At the same time, the responses of the same neurons to iontophoretically applied NMDA or kainic acid were not consistently inhibited. The inhibition of heat-evoked responses by PAG BIC was reversed by iontophoretic application of the selective μ-opioid receptor antagonists, D- Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and D-Phe-Cys-Tyr-D-Trp-Arg- Thr-Pen-Thr-NH2 (CTAP). A similar effect was produced by naloxone; however, naloxone had an excitatory influence on dorsal horn neurons in the absence of PAG-evoked descending inhibition. This is the first demonstration that endogenous opioids acting via spinal μ-opioid receptors contribute to brain stem control of nociceptive spinal dorsal horn neurons. The inhibition appears to result in part from presynaptic inhibition of afferents to dorsal horn neurons.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalJournal of Neurophysiology
Volume79
Issue number2
Publication statusPublished - Feb 1998

Fingerprint

Posterior Horn Cells
Periaqueductal Gray
Nociceptors
Opioid Peptides
Opioid Receptors
Mesencephalon
Bicuculline
Naloxone
Opioid Analgesics
Hot Temperature
Neurons
Narcotic Antagonists
Kainic Acid
Microinjections
Interneurons
N-Methylaspartate
Analgesia
Heating
Brain Stem
Spinal Cord Dorsal Horn

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Endogenous opioid peptides acting at μ-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons. / Budai, D.; Fields, Howard L.

In: Journal of Neurophysiology, Vol. 79, No. 2, 02.1998, p. 677-687.

Research output: Contribution to journalArticle

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