NMDA Receptors and Colitis: Basic Science and Clinical Implications.

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.

Hypersensitivity to cutaneous thermal nociceptive stimuli in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common intestinal ailment of which the pathophysiological mechanisms are not well understood. Most IBS patients demonstrate enhanced perception, visceral hypersensitivity, in response to distension of the gut lumen but there are conflicting results about changes in somatic sensitivity. This study focused on the possible contribution of abnormal pain sensitization due to positive feedback (vicious pain cycle) that affects somatic tissues due to viscero-somatic convergence. The specific objectives were to measure cutaneous thermal pain sensitivity along the segmental axis, including in dermatomes that are remote from the visceral pain focus. Pain sensitivity was probed with cutaneous thermal stimulation to the lower and upper extremities and the face in nine diarrhea-predominant IBS patients (diagnosed with ROME II criteria) and 12 healthy female controls. The stimuli were administered with a contact thermode, assuring that size of the stimulated area and stimulus duration were clearly defined and identical in all locations. Sensitization of IBS patients was not limited to symptomatic dermatomes (calf) but extended evenly across the body, including to the face (no sensitization gradient from foot to face). Also, the difference between IBS and control groups did not depend on the evoked pain intensity level, i.e. the degree of sensitization of IBS patients was similar near threshold (10% on the visual analog scale) and at higher intensities. Lastly, no correlation was found between IBS subjects' pain sensitivity of any of the three test sites and their ratings of spontaneous pain.