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| NMDA-receptor regulation of substance P release from primary afferent nociceptors |
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| Author(s): Liu HT, Mantyh PW, Basbaum AI |
| Source: NATURE Volume: 386 Issue: 6626 Pages: 721-724 Published: APR 17 1997 |
| Times Cited: 246 References: 28 |
| 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(1). 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(2), 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 prespnaptic 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF SAN FRANCISCO, DEPT ANAT, SAN FRANCISCO, CA 94143 USA
2. UNIV CALIF SAN FRANCISCO, DEPT PHYSIOL, SAN FRANCISCO, CA 94143 USA
3. UNIV CALIF SAN FRANCISCO, WM KECK FDN CTR INTEGRAT NEUROSCI, SAN FRANCISCO, CA 94143 USA
4. UNIV MINNESOTA, MOL NEUROBIOL LAB, VET ADM MED CTR, MINNEAPOLIS, MN 55417 USA
5. UNIV MINNESOTA, DEPT PSYCHIAT, MINNEAPOLIS, MN 55417 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: WU387 |
| ISSN: 0028-0836 |
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