Spence VA, Khan F, Belch JJF


Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee, UK


Cholinergic mechanisms are important in the control of peripheral skin perfusion and, in part, are regulated by endothelial cells. Following development of a method for assessing endothelial function by acetylcholine iontophoresis and laser Doppler imaging, and the testing of the method on patients with cardiovascular disease, this methodology was applied to ME/CFS patients to test whether the reported evidence of central nervous system cholinergic sensitivity in these patients is widespread.

Methods and results

From 420 members of a local ME/CFS self-help group, 22 patients (7 men and 15 women, mean ± SD age 45 ± 9 years, range 26 to 59 years) who fulfilled the Centers for Disease Control criteria for chronic fatigue syndrome, were enrolled. Iontophoresis was used to transport acetylcholine and sodium nitroprusside, in 1% solution, across intact skin in graded doses using a 0.1-mA anodal current. A laser Doppler imager (Moor Instruments, Axminster, United Kingdom) that scans a low-power laser beam over the skin surface measured skin blood flow. The vascular responses to acetylcholine were significantly greater in patients with chronic fatigue syndrome than in control subjects at all 4 doses. (p=0.01, ANOVA), in contrast with vascular responses to sodium nitroprusside which did not differ significantly between the groups.


The results of this study show enhanced cholinergic activity in the peripheral microcirculation of patients with ME/CFS. This enhancement was specific for acetylcholine. We could not determine why the patients have acetylcholine supersensitivity in the skin microcirculation. However, many of the symptoms of chronic fatigue syndrome, such as temperature sensitivity, gastrointestinal difficulties, problems with sleep, and orthostatic intolerance, are consistent with altered cholinergic activity, and the findings might have important implications for features of chronic fatigue syndrome that involve vascular integrity.


American Journal of Medicine, 2000 Jun 15; 108(9): 736–9
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Non-technical summary

Acetylcholine is a chemical found in the nervous system which helps transmit nerve impulses from the brain around the body. Brain scans have shown that people with ME/CFS may be abnormally sensitive to acetylcholine, and this could help explain many of the symptoms they experience.

Acetylcholine is also found in the lining of blood vessels, and can influence the flow of blood through an artery by relaxing its walls so that its diameter increases. By stimulating the skin with small amounts of acetylcholine, and measuring the resulting changes in blood flow, we were able to test the sensitivity of blood vessels in the forearm. We found that people with ME/CFS were more sensitive to acetylcholine than were healthy people of the same age.

Sensitivity to acetylcholine may be an important feature of ME/CFS, and this abnormality may have an impact on the health of the heart and circulation of people with the condition.