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Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus.
Eur J Neurosci. 2004 Apr; 19(8):2009-16.EJ

Abstract

Activation of afferent nociceptive pathways is subject to activity-dependent plasticity, which may manifest as windup, a progressive increase in the response of dorsal horn nociceptive neurons to repeated stimuli. At the cellular level, N-methyl-d-aspartate (NMDA) receptor activation by glutamate released from nociceptive C-afferent terminals is currently thought to generate windup. Most of the wide dynamic range nociceptive neurons that display windup, however, do not receive direct C-fibre input. It is thus unknown where the NMDA mechanisms for windup operate. Here, using the Sprague-Dawley rat trigeminal system as a model, we anatomically identify a subpopulation of interneurons that relay nociceptive information from the superficial dorsal horn where C-fibres terminate, to downstream wide dynamic range nociceptive neurons. Using in vivo electrophysiological recordings, we show that at the end of this pathway, windup was reduced (24 +/- 6%, n = 7) by the NMDA receptor antagonist AP-5 (2.0 fmol) and enhanced (62 +/- 19%, n = 12) by NMDA (1 nmol). In contrast, microinjections of AP-5 (1.0 fmol) within the superficial laminae increased windup (83 +/- 44%, n = 9), whereas NMDA dose dependently decreased windup (n = 19). These results indicate that NMDA receptor function at the segmental level depends on their precise location in nociceptive neural networks. While some NMDA receptors actually amplify pain information, the new evidence for NMDA dependent inhibition of windup we show here indicates that, simultaneously, others act in the opposite direction. Working together, the two mechanisms may provide a fine tuning of gain in pain.

Authors+Show Affiliations

INSERM E216 Neurobiologie de la douleur trigéminale, Faculté de Chirurgie Dentaire, 11 boulevard Charles de Gaulle, 63000 Clermont-Ferrand, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15090028

Citation

Woda, Alain, et al. "Bidirectional Modulation of Windup By NMDA Receptors in the Rat Spinal Trigeminal Nucleus." The European Journal of Neuroscience, vol. 19, no. 8, 2004, pp. 2009-16.
Woda A, Blanc O, Voisin DL, et al. Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus. Eur J Neurosci. 2004;19(8):2009-16.
Woda, A., Blanc, O., Voisin, D. L., Coste, J., Molat, J. L., & Luccarini, P. (2004). Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus. The European Journal of Neuroscience, 19(8), 2009-16.
Woda A, et al. Bidirectional Modulation of Windup By NMDA Receptors in the Rat Spinal Trigeminal Nucleus. Eur J Neurosci. 2004;19(8):2009-16. PubMed PMID: 15090028.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus. AU - Woda,Alain, AU - Blanc,Olivier, AU - Voisin,Daniel L, AU - Coste,Jérôme, AU - Molat,Jean-Louis, AU - Luccarini,Philippe, PY - 2004/4/20/pubmed PY - 2004/6/23/medline PY - 2004/4/20/entrez SP - 2009 EP - 16 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 19 IS - 8 N2 - Activation of afferent nociceptive pathways is subject to activity-dependent plasticity, which may manifest as windup, a progressive increase in the response of dorsal horn nociceptive neurons to repeated stimuli. At the cellular level, N-methyl-d-aspartate (NMDA) receptor activation by glutamate released from nociceptive C-afferent terminals is currently thought to generate windup. Most of the wide dynamic range nociceptive neurons that display windup, however, do not receive direct C-fibre input. It is thus unknown where the NMDA mechanisms for windup operate. Here, using the Sprague-Dawley rat trigeminal system as a model, we anatomically identify a subpopulation of interneurons that relay nociceptive information from the superficial dorsal horn where C-fibres terminate, to downstream wide dynamic range nociceptive neurons. Using in vivo electrophysiological recordings, we show that at the end of this pathway, windup was reduced (24 +/- 6%, n = 7) by the NMDA receptor antagonist AP-5 (2.0 fmol) and enhanced (62 +/- 19%, n = 12) by NMDA (1 nmol). In contrast, microinjections of AP-5 (1.0 fmol) within the superficial laminae increased windup (83 +/- 44%, n = 9), whereas NMDA dose dependently decreased windup (n = 19). These results indicate that NMDA receptor function at the segmental level depends on their precise location in nociceptive neural networks. While some NMDA receptors actually amplify pain information, the new evidence for NMDA dependent inhibition of windup we show here indicates that, simultaneously, others act in the opposite direction. Working together, the two mechanisms may provide a fine tuning of gain in pain. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/15090028/Bidirectional_modulation_of_windup_by_NMDA_receptors_in_the_rat_spinal_trigeminal_nucleus_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0953-816X&date=2004&volume=19&issue=8&spage=2009 DB - PRIME DP - Unbound Medicine ER -