NMDA Receptors and Colitis: Basic Science and Clinical Implications

Abstract

During the last decade, research focusing primarily on alterations in the peripheral and central nervous system has improved our understanding of the pathophysiological mechanisms of chronic visceral pain. These studies have demonstrated significant physiological changes following injury to the viscera in the firing patterns of both primary afferent neurons that transmit nociceptive information from the viscera and in central neurons that process the nociceptive information. A number of receptors, neurotransmitters, cytokines, and second messenger systems in these neurons have been implicated in the enhancement of visceral nociception. N-methyl-d-aspartic acid (NMDA) receptors play an important role in chronic visceral pain and hypersensitivity that is present in the setting of colonic inflammation. NMDA receptors are found in the peripheral nervous system as well as the central terminal of primary afferent neurons and have been shown to play an important role in regulating the release of nociceptive neurotransmitters. Recent work has demonstrated the presence of NMDA receptors in the enteric nervous system. In this article, we will discuss more recent evidence of the role of NMDA receptors in visceral pain associated with colitis.

Figure 1

The figure depicts inflammatory mediators in colonic inflammation that lead to visceral pain. These mediators sensitize nociceptors, activate NMDA receptors, and affect nociceptive processing pathways that lead to visceral hypersensitivity and abdominal pain.