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.
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