Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with CFS 2003 Khan, Spence et al

Summary
Although the aetiology of chronic fatigue syndrome (CFS) is unknown, there have been a number of reports of blood flow abnormalities within the cerebral circulation and systemic blood pressure defects manifesting as orthostatic intolerance. Neither of these phenomena has been explained adequately, but recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism.

Our group has previously reported enhanced skin vasodilatation in response to cumulative doses of transdermally applied acetylcholine (ACh), implying an alteration of peripheral cholinergic function. To investigate this further, we studied the time course of ACh-induced vasodilatation following a single dose of ACh in 30 patients with CFS and 30 age- and gender-matched healthy control subjects. No differences in peak blood flow was seen between patients and controls, but the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects. The time taken to decay to 75% of the peak response in patients and controls was 13·7 ± 11·3 versus 8·9 ± 3·7 min (P = 0·03), respectively, and time taken to decay to 50% of the peak response was 24·5 ± 18·8 versus 15·1 ± 8·9 min (P = 0·03), respectively. Prolongation of ACh-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.

Paywall, https://onlinelibrary.wiley.com/doi/10.1046/j.1475-097X.2003.00511.x

 

Prior study: Enhanced sensitivity of the peripheral cholinergic vascular response in patients with chronic fatigue syndrome (2000, The American Journal of Medicine)

 

Also from the same stable:

Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome, 2003, Spence et al

and

Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure, 2004, Khan et al

Don't think it needs its own thread but full text available here (the other 3 papers are all on SciHub). The 4 papers can be viewed as a set.

The experiments reported seem to be well-conducted, albeit too small, Fukuda but 100% of the CFS cohort had PEM, and with some intriguing findings. The studies looked at the vasodilation effect of acetylcholine, rather than its neurotransmitter action.

As far as I can tell, while the group have replicated their own findings, there hasn't been replication by other groups, and the findings don't seem to have had much impact, going by number of citations in subsequent studies (admittedly I haven't looked very hard so might have missed something)

Any reason why these findings weren't pursued more vigorously after this group stopped working on them? Beyond charity funding running out