Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats

James A. McRoberts, Santosh V. Coutinho, Juan Carlos G. Marvizón, Eileen F. Grady, Michele Tognetto, Jyoti N. Sengupta, Helena S. Ennes, Victor V. Chaban, Silvia Amadesi, Christophe Creminon, Tom Lanthorn, Pierangelo Geppetti, Nigel W. Bunnett, Emeran A. Mayer

Research output: Contribution to journalArticle

Abstract

Background & Aims: N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that have an important role in long-term potentiation and memory processing in the central nervous system. The aims in this study were to determine whether NMDA receptors are expressed in the peripheral nervous system and identify their role in mediating behavioral pain responses to colonic distention in the normal gut. Methods and Results: Immunohistochemical localization of the NR1 subunit showed that NMDA receptors are expressed on the cell bodies and peripheral terminals of primary afferent nerves innervating the colon. Dorsal root ganglia neurons retrogradely labeled from the colon in short-term culture responded to addition of NMDA with increased intracellular [Ca2+]. Activation of peripheral NMDA receptors in colonic tissue sections caused Ca2+-dependent release of the proinflammatory neuropeptides, calcitonin gene-related peptide and substance P. Behavioral pain responses to noxious mechanical stimulation were inhibited in a reversible, dose-dependent manner by intravenous administration of memantine, a noncompetitive antagonist of the NMDA receptor. Single fiber recordings of decentralized pelvic nerves showed that colorectal distention responsive afferent nerve activity was inhibited by memantine. Conclusions: Peripheral NMDA receptors are important in normal visceral pain transmission, and may provide a novel mechanism for development of peripheral sensitization and visceral hyperalgesia.

Original languageEnglish (US)
Pages (from-to)1737-1748
Number of pages12
JournalGastroenterology
Volume120
Issue number7
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    McRoberts, J. A., Coutinho, S. V., Marvizón, J. C. G., Grady, E. F., Tognetto, M., Sengupta, J. N., Ennes, H. S., Chaban, V. V., Amadesi, S., Creminon, C., Lanthorn, T., Geppetti, P., Bunnett, N. W., & Mayer, E. A. (2001). Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats. Gastroenterology, 120(7), 1737-1748. https://doi.org/10.1053/gast.2001.24848