over. Conversely, anxiety about an injury and hypervigilance to the affected part can lead to increased pain. In CMI, central factors may lead to a lower sensation threshold and, if this is the case, centrally targeted treatments would probably have therapeutic value by increasing sensation thresholds, as occurs in treatment for other conditions, such as fibromyalgia, CFS, and IBS. There is some evidence that patients who have similar somatic symptoms have higher concentrations of substance P (which transmits pain) in their blood and cerebrospinal fluid than people who do not have such symptoms (Clauw, 2009). In those patients, direct pressure on the skin or inflation of a balloon in the esophagus causes pain at a much lower level of pressure than in people who do not have these somatic symptoms.

In addition, central measures of hormonal stress, such as an altered response of the hypothalamic-pituitary-adrenal axis, reveal an inappropriate flattened response to additional stress that may reflect a more sustained central overactivity in patients who have visceral hypersensitivity (such as IBS) or somatic hypersensitivity (such as fibromyalgia) (Clauw, 2009).

Nonrestorative sleep can be reproduced in normal volunteers who are subjected to disruption of deep stage four sleep and is a typical sleep pattern in patients who have IBS. When deep stage four sleep is repeatedly disrupted, affected people can develop myalgia, heightened pain, presence of tender points on examination, and disrupted sleep patterns afterward. Further research is needed to assess whether use of programs and agents that restore a better sleep pattern may also lead to improvement in other symptoms.

In summary, the multiple symptoms of CMI, like the symptoms associated with other functional somatic syndromes, may arise from at least two factors: an impairment of the brain in its downregulating of incoming nerve signals originating in the body and an increase in or amplification of bodily nerve signals for any of a variety of reasons (such as injury or infection). The degree to which those factors interact in CMI is an important topic for future research.


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Clauw, D. J. 2009. Fibromyalgia: An overview. American Journal of Medicine 122(12 Suppl.):S3-S13.

Dantzer, R., J. C. O’Connor, G. G. Freund, R. W. Johnson, and K. W. Kelley. 2008. From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience 9(1):46-56.

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IOM (Institute of Medicine). 2008. Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-related Stress. Washington, DC: The National Academies Press.

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