NMDA-receptor regulation of substance P release from primary afferent nociceptors

Hantao Liu, Patrick W Mantyh, Allan I. Basbaum

Research output: Contribution to journalArticle

332 Citations (Scopus)

Abstract

Severe or prolonged tissue or nerve injury can induce hyperexcitability of dorsal horn neurons of the spinal cord, resulting in persistent pain, an exacerbated response to noxious stimuli (hyperalgesia), and a lowered pain threshold (allodynia). These changes are mediated by NMDA (N-methyl-D- aspartate)-type glutamate receptors in the spinal cord. Here we report that activation of the NMDA receptor causes release of substance P, a peptide neurotransmitter made by small-diameter, primary, sensory 'pain' fibres. Injection of NMDA in the cerebrospinal fluid of the rat spinal cord mimicked the changes that occur with persistent injury, and produced not only pain, but also a large-scale internalization of the substance P receptor into dorsal horn neurons, as well as structural changes in their dendrites. Both the pain and the morphological changes produced by NMDA were significantly reduced by substance P-receptor antagonists or by elimination of substance P-containing primary afferent fibres with the neurotoxin capsaicin. We suggest that presynaptic NMDA receptors located on the terminals of small- diameter pain fibres facilitate and prolong the transmission of nociceptive messages, through the release of substance P and glutamate. Therapies directed at the presynaptic NMDA receptor could therefore ameliorate injury- evoked persistent pain states.

Original languageEnglish (US)
Pages (from-to)721-724
Number of pages4
JournalNature
Volume386
Issue number6626
StatePublished - Apr 17 1997
Externally publishedYes

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Nociceptors
Substance P
N-Methyl-D-Aspartate Receptors
Pain
Posterior Horn Cells
Spinal Cord
Hyperalgesia
N-Methylaspartate
Wounds and Injuries
Neurokinin-1 Receptor Antagonists
Neurokinin-1 Receptors
Nerve Tissue
Pain Threshold
Capsaicin
Neurotoxins
Glutamate Receptors
Dendrites
Neurotransmitter Agents
Cerebrospinal Fluid
Glutamic Acid

ASJC Scopus subject areas

  • General

Cite this

NMDA-receptor regulation of substance P release from primary afferent nociceptors. / Liu, Hantao; Mantyh, Patrick W; Basbaum, Allan I.

In: Nature, Vol. 386, No. 6626, 17.04.1997, p. 721-724.

Research output: Contribution to journalArticle

Liu, Hantao ; Mantyh, Patrick W ; Basbaum, Allan I. / NMDA-receptor regulation of substance P release from primary afferent nociceptors. In: Nature. 1997 ; Vol. 386, No. 6626. pp. 721-724.
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