Development Of a Mouse Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex clinical condition characterized by overwhelming fatigue and associated symptoms like pain lasting greater than 6 months. ME/CFS is often initiated after an illness, exacerbated by stress, and associated with immune system changes. The purpose of this study was to develop a clinically relevant mouse model of ME/CFS. We hypothesized that pairing stress with an illness-like immune stimulation would generate long-term fatigue and pain, and thus tested effects of combining one-day of acute restraint stress with the immune activator lipopolysaccharide (LPS, i.p.). Fatigue was assessed using voluntary wheel running (RW) and open field testing. For pain, we assessed mechanical paw sensitivity and muscle withdrawal thresholds. Immune cell phenotype was assessed using spectral flow cytometry. C57BL6 mice were divided into 4 groups: (1) stress+LPS, (2) stress+saline, (3) stress+saline+1-day no-RW, (4) no intervention. The stress+LPS group showed a short duration decrease in RW (p<0.001), open field activity (p<0.001), and muscle withdrawal threshold (p=0.005). Surprisingly, the stress and saline group ran significantly less over the 12-day period showing a long-lasting decrease in RW when compared to the other three groups (p=0.002) without changes in open field or pain behaviors long-term (day 10). The stress+LPS group showed alterations in immune phenotypes: increased CD4+ T-cells (p<0.001), decreased CD8+ T-cells (p=0.007), and decreased CD25+ T-cells (p=0.02) compared to no intervention group. Thus, stress with a mild insult produces a long-term reduction in activity that is not associated with alterations in immune cell phenotype. Funded by the Foundation for Physical Therapy Research: PODS I and II.