Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study

Background: Commonalities in the core symptoms of fatigue and cognitive dysfunction experienced by chronic fatigue syndrome (CFS, also known as ME) and multiple sclerosis (MS) patients have been described. Many CFS and MS patients also experience chronic pain, which has been attributed to central sensitization in both groups of patients. However, the characteristics of pain in CFS and MS patients have not been compared. Objectives: To compare experimental pain measurements in patients with CFS or MS and healthy controls. Study design: Observational study. Setting: This study took place in Belgium at Vrije Universiteit Brussel and the University of Antwerp. Methods: Pressure pain thresholds, temporal summation, conditioned pain modulation, and occlusion cuff pressure thresholds rated as painful (1st cuff pressure threshold) and as 3/10 on a verbal numerical scale (2nd cuff pressure threshold) were measured in patients with CFS (n = 48), MS (n = 19) and healthy pain-free controls (n = 30). Adjusted between-group differences were estimated using linear regression models. Results: Finger pain pressure thresholds of patients with CFS, compared with patients with MS, were 25% lower (difference ratio 0.75 [95% CI 0.59, 0.95], P = 0.02) and shoulder pain pressure thresholds were 26% lower (difference ratio 0.74 [0.52, 1.04], P = 0.08). Compared with patients with MS, patients with CFS had 29% lower first cuff pressure threshold (difference ratio 0.71 [0.53, 0.94], P = 0.02) and 41% lower 2nd cuff pressure threshold (0.59 [0.41, 0.86], P = 0.006). Finger temporal summation was higher in patients with CFS than in patients with MS (mean difference 1.15 [0.33, 1.97], P = 0.006), but there were no differences in shoulder temporal summation or conditioned pain modulation at either site. Differences between patients with CFS and MS tended to be greater than between either patient group and healthy controls. Pain pressure thresholds and cuff pressure thresholds tended to be positively correlated, and temporal summation negatively correlated, with higher physical function and lower fatigue in both groups of patients. Subjective pain in patients with CFS but not in patients with MS was strongly negatively correlated with pain pressure thresholds and cuff pressure thresholds, and positively correlated with temporal summation. Limitations: The main limitations of our study are the relatively small sample sizes, its crosssectional design, and its exploratory nature. Conclusions: We found differences in the characteristics of pain symptoms reported by patients with CFS and patients with MS, which suggest different underlying mechanisms. Specifically, overactive endogenous pain facilitation was characteristic of pain in patients with CFS but not in patients with MS, suggesting a greater role for central sensitization in CFS. Keywords: Chronic fatigue syndrome, CFS/ME, multiple sclerosis, experimental pain, central sensitization