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  1. J. Eccles1,2,
  2. C. Thompson3,4,
  3. B. Thompson1,
  4. M. Amato1,
  5. K. Themelis1,5,
  6. H. Critchley1,
  7. N. Harrison1,6,
  8. K. Davies4
  1. 1Brighton & Sussex Medical School, Neuroscience, Falmer, United Kingdom
  2. 2University Hospitals Sussex NHS Foundation Trust, CIRU, Brighton, United Kingdom
  3. 3University Hospitals Sussex NHS Foundation Trust, Rheumatology, Brighton, United Kingdom
  4. 4Brighton & Sussex Medical School, Clinical and Experimental Medicine, Falmer, United Kingdom
  5. 5University of Warwick, Psychology, Coventry, United Kingdom
  6. 6University of Cardiff, CUBRIC, Cardiff, United Kingdom


Background Fibromyalgia and ME/CFS are multifaceted conditions with overlapping symptoms(1); the pathoaetiological mechanisms are complex and debated(2), however there is a strong association with features of hereditary disorders of connective tissue (hypermobility) and autonomic and inflammatory abnormalities (1,2).

Objectives To determine potential autonomic and inflammatory mechanisms of pain and fatigue in fibromyalgia and ME/CFS

Methods After excluding participants with WCC higher than 10 (suggesting acute infection) baseline markers of inflammation (CRP and ESR) were available for 60 patients with confirmed diagnoses of Fibromyalgia and/ or ME/CFS and 23 matched controls. Participants then underwent full research diagnostic evaluation including a hypermobility assessment(1) and autonomic challenge (60 degree head up tilt, ISRCTN78820481). Subjective pain and fatigue were assessed before and after challenge (VAS). Linear regression models were used to explore predictors, with adjustment for confounders as appropriate. Mediation analyses (looking for mechanistic effects) were conducted according to the method of Hayes (3) and mediation considered significant if bootstrapped confidence intervals of the estimated indirect effect did not cross zero. In these mediation analyses predictor variable was group membership (patient or control), outcome variable was change in 1)pain and 2)fatigue induced by challenge and mediatiors 1)no of connective tissue features in hypermobility diagnostic criteria endorsed by participant; 2)baseline inflammatory markers.

Results ESR and CRP were significantly higher in patients rather than controls, even after correcting for BMI, age and sex (B=5.15, t=2.05, p=0.044; B=1.77, t=2.15, p=0.044 respectively). Adjusted ESR and CRP correlated with both subjective fatigue (B=0.44, t=2.09, p=0.04; B=1.63, t=2.60, p=0.011) and pain severity (B=0.13, t=2.51, p=0.014; B=0.45, t=3.01, p=0.004) at baseline. Autonomic challenge amplified pain (B=14.20, t=2.87, p=0.005) and fatigue (B=31.48, t=5.95, p=<0.001) in patients to a significantly greater degree than controls, controlling for baseline levels. Baseline ESR and CRP also predicted challenge-induced increase in fatigue (B=0.78, t=370, p=<0.001; B=1.91, t=3.36, p=<0.001) and ESR challenge-induced increases in pain (B=0.46, t=2.35, p=0.021).

Mediation analysis demonstrated that number of connective tissue features expressed in hypermobility criteria mediated the degree to which subjective pain was increased by the autonomic challenge (Bootstraped 95% CI of indirect effect do not cross zero, 0.1572 – 6.8171). ESR mediated the degree to which subjective fatigue was increased by the autonomic challenge (Bootstraped 95% CI of indirect effect do not cross zero,0.7541 – 7.3888).

Conclusion To our knowledge this is the first study to directly explore autonomic and inflammatory mechanisms of pain and fatigue in a combined population of Fibromyalgia and ME/CFS. This study this adds to the evidence-base of baseline inflammatory abnormalities in fibromyalgia and ME/CFS. It highlights their potential role in predicting symptom severity and their potential mechanistic role in autonomic induced pain and fatigue, suggesting future treatment strategies.

References [1]Eccles JA, Thompson B, Themelis K, Amato ML, Stocks R, Pound A, et al. Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study. Clin Med (Lond). 2021;21(1):53-8.

[2]Eccles JA, Davies KA. The challenges of chronic pain and fatigue. Clin Med (Lond). 2021;21(1):19-27.

[3]Hayes AF. Partial, conditional, and moderated moderated mediation: Quantification, inference, and interpretation. Commun Monogr. 2018;85(1):4-40.

Disclosure of Interests Jessica Eccles: None declared, Charlotte Thompson: None declared, Beth Thompson: None declared, Marisa Amato: None declared, Kristy Themelis: None declared, Hugo Critchley: None declared, Neil Harrison Grant/research support from: speakers bureau, Kevin Davies: None declared

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