Development of a Mouse Model for Chronic Fatigue Syndrome

The purpose of this study was to develop a clinically relevant mouse model of CFS to allow for the testing of underlying mechanisms and development of novel treatment interventions. Mice were injected with either lipopolysaccharide (LPS) or Poly I:C systemically (0.1- 1.0 mg/kg LPS, i.p. or 0.6-6mg/kg Poly I:C) and compared to a vehicle control injection. To test for fatigue-like behaviors, we examined voluntary wheel running (VWR) and open field activity. To test for pain-like behaviors, muscle withdrawal thresholds (MWT) and mechanical sensitivity of the paw. Measurements were assessed before and up to 1 week after injection of LPS or Poly I:C. Differences in voluntary running wheel data were assessed using mixed model analysis for differences between dose, time and an interaction between dose and time. Differences in open field parameters, MWT, and paw sensitivity between groups were assessed using repeated measures ANOVAs. Running wheel activity was reduced after injection of either LPS or Poly I:C (χ2=15.4; p=0.003). LPS reduced running wheel activity on days 1-3 for the 1.0 mg/kg dose of LPS and on Day 1 for Poly I:C when compared to vehicle (p<0.001). Lower doses of LPS showed faster recovery to baseline. For the open field testing, LPS reduced in distance travelled (F=9.1; p<0.001), increase in time standing still (F=6.5, p=0.001) but not time in center (F= 1.1, p=0.36) 24h after infection. Post-hoc testing (Tukey's test) showed a significant difference between the vehicle and the 1.0 mg/kg group of LPS (p=0.001). Similar reductions were observed for the 6 mg/kg group of Poly I:C (p<0.001). For pain behaviors, there was no difference between groups in the MWT or paw sensitivity (p>0.05) for either LPS or Poly I:C. These results show that a single injection of an infectious agent reduces physical activity and exploratory behavior, but does not produce pain behaviors.