Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia

Amber A Surian,James N Baraniuk

doi:10.1038/s41598-020-62771-9

Abstract

Pain is a diagnostic criterion for Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and fibromyalgia (FM). The physical sign of systemic hyperalgesia (tenderness) was assessed in 920 women who were stratified by 2000 Kansas GWI, 1994 CFS, and 1990 FM criteria. Pressure was applied by dolorimetry at 18 traditional tender points and the average pressure causing pain determined. GWI women were the most tender (2.9 ± 1.6 kg, mean ± SD, n = 70), followed by CFS/FM (3.1 ± 1.4 kg, n = 196), FM (3.9 ± 1.4 kg, n = 56), and CFS (5.8 ± 2.1 kg, n = 170) compared to controls (7.2 ± 2.4 kg, significantly highest by Mann-Whitney tests p < 0.0001, n = 428). Receiver operating characteristics set pressure thresholds of 4.0 kg to define GWI and CFS/FM (specificity 0.85, sensitivities 0.80 and 0.83, respectively), 4.5 kg for FM, and 6.0 kg for CFS. Pain, fatigue, quality of life, and CFS symptoms were equivalent for GWI, CFS/FM and CFS. Dolorimetry correlated with symptoms in GWI but not CFS or FM. Therefore, women with GWI, CFS and FM have systemic hyperalgesia compared to sedentary controls. The physical sign of tenderness may complement the symptoms of the Kansas criteria as a diagnostic criterion for GWI females, and aid in the diagnosis of CFS. Molecular mechanisms of systemic hyperalgesia may provide new insights into the neuropathology and treatments of these nociceptive, interoceptive and fatiguing illnesses.

Highlights

An alternative approach to distinguish between Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS) and FM may be to assess the sign of systemic hyperalgesia, the perception of physical discomfort elicited by pressure stimulation[10]
Three approaches were used to classify the women into GWI, CFS alone, FM alone, overlapping CFS plus FM (CFS/ FM), and sedentary control (SC) groups
We proposed that the distributions of systemic hyperalgesia would stratify these clinical groups despite their symptomatic overlap

Summary

Introduction

An alternative approach to distinguish between GWI, CFS and FM may be to assess the sign of systemic hyperalgesia, the perception of physical discomfort elicited by pressure stimulation[10]. A confounding design in studies of hyperalgesia is to compare dolorimetry between tender (e.g. defined using 1990 FM criteria5) versus nontender (general population) groups. Such a study design ensures a floor effect for pressures that cause pain in FM, a ceiling effect in the control group, and demarcation of a threshold of ~4 kg for separating the 2 groups. We avoided this confound by not using tenderness to define CFS or GWI status. The clinical implication was that the physical sign of tenderness may have potential as a diagnostic criterion in these conditions

Methods

Results

Conclusion