Autonomic and inflammatory mechanisms of pain and fatigue i nfibromyalgia and ME/CFS: an interventional study

Background: Fibromyalgia and ME/CFS are complex disorders with overlapping symptoms; the pathoaetiology and clinical distinction are debated, however inflammatory and autonomic abnormalities are observed. Objectives: To investigate the role of inflammatory and autonomic nervous system responses in mechanisms of pain and fatigue in fibromyalgia and ME/CFS Methods: 63 patient participants with clinical diagnoses of fibromyalgia and/or ME/CFS were recruited into a multi-stage interventional study (ISRCTN78820481) alongside 24 healthy controls. All underwent research diagnostic criteria evaluation. The majority underwent autonomic challenge (60 degree head up tilt) and/or inflammatory challenge (placebo-controlled typhoid vaccination) with baseline characterisation of symptoms, inflammatory markers and pre-post measures of pain and fatigue. Results: Of the 63 patients, 32% of patients had received a clinical diagnosis of Fibromyalgia; 38% ME/CFS and 30% dual diagnoses. Following research evaluation 89% met ACR diagnostic criteria for fibromyalgia; 94% Canadian Criteria for ME/CFS; 97% Fukada Criteria for ME/CFS There was a significantly higher ESR in patients compared to controls (p= 0.036). There was a trend towards higher CRP in patients compared to controls (p= 0.076). ESR correlated with baseline pain score (r=0.309, p=0.011), fatigue severity (r=0.262, p=0.032), fatigue impact (r=0.382, p=0.014) change in fatigue score induced by tilt (r=0.319, p=0.011) and change in pain score induced by placebo-controlled inflammation (r=-0.279, p=0.043). Similarly CRP level correlated with baseline pain score (r=0.340, p=0.005), fatigue impact (r=0.439, p=0.004), change in fatigue (r=-0.277, p=0.045) and pain score (r=-0.394, p=0.014) induced by placebo-controlled inflammation and change in pressure pain theshold induced by tilt (r=0.286, p=0.027). Baseline IL6 was higher in patients than controls (p = 0.002), correlating with baseline pain score (r = 0.345, p = 0.002) and change in pain score induced by tilt (r=0.281, p=0.21). Change in IL6 induced by inflammatory challenge correlated with inflammation induced fatigue score (r = 0.378, p = 0.01). Conclusion: Inflammatory and autonomic mechanisms contribute to pain and fatigue in this frequently overlooked patient group, highlighting possibilities for targeted treatments. Such data will be enriched going forward by neuroimaging and transcriptomic insights.