Neural Mechanisms of Hyperalgesia in Irritable Bowel Syndrome Three Possible General Mechanisms Underlying Hyperalgesia

These studies of animal models of IBS clearly point to a spinal mechanism, consistent with the observation that IBS patients have enhanced responses to visceral and cutaneous stimuli throughout the pain matrix of the brain (including thalamus). However, based on the evidence presented so far, it is not entirely clear the extent to which these enhanced responses are the result of (i) a facilitating mechanism confined within the brain, (ii) a spinal sensitization maintained by tonic impulse input from the rectum and/or colon, or (iii) a mechanism of descending facilitation from the brain to the spinal cord and/or gut. The first few neuroimaging studies to compare IBS with normal controls' brain responses to visceral stimulation produced mixed results that are difficult to interpret, including reduced anterior cingulate cortex (ACC) responses in IBS patients and increased responses in a limited number of regions in IBS

patients (57-59). The enhancement in regions such as rostral ACC and prefrontal cortical areas provides limited support for the idea that enhanced pain in IBS is the result of cognitive enhancement rather than enhancement of activity in ascending pathways to the brain. Abnormally enhanced responses in ACC and prefrontal areas would be consistent with a cognitive enhancement mechanism (57). However, as described above, later studies found that IBS patients showed enhanced brain activations within multiple pain processing areas, including those at early levels of pain processing (51,60). These studies used higher numbers of subjects and possibly improved methods of brain imaging. Most critically, the results of later imaging studies are consistent with studies of animal models of IBS that show enhanced responses at the spinal cord level (55). Nevertheless, these three alternative mechanisms—tonic peripheral impulse input, descending facilitation, and intracerebral enhancement are not mutually exclusive and we need tests to determine the relative contribution of these general factors.

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