Suppression of Voluntary Wheel Running in Rats Is Dependent on the Site of Inflammation: Evidence for Voluntary Running as a Measure of Hind Paw-Evoked Pain

Decreased voluntary wheel running has recently been proposed as a preclinical pain measure for inflammatory pain, but whether this reflects pain evoked by use of the affected limbs is unknown. To assess the role of inflammation site as a determinant of this measure, complete Freund's adjuvant (CFA), formalin, or equivolume vehicle was subcutaneously injected into the plantar surface of the hind paws (bilateral) or L1 dorsum dermatome (leaving paws unaffected) of male Sprague Dawley rats. CFA-induced hind paw mechanical allodynia (P < .001) did not correlate with reduced voluntary wheel running. Intraplantar formalin did not attenuate voluntary running, despite eliciting robust licking/writhing/flinching behavior and hind paw mechanical allodynia (P < .001). Subcutaneous L1 dorsum dermatome formalin, but not CFA, induced licking/writhing/flinching behavior (P < .001), but neither induced hind paw mechanical allodynia or attenuated voluntary running. That voluntary running is decreased by hind paw CFA, but not by L1 dorsum CFA, implies that the behavior is a measure of CFA-induced pain evoked by use of the affected limbs rather than supraspinal pain processing that is independent of inflammation site. Furthermore, the results suggest that interpretation of voluntary wheel running data cannot simply be explained by correlation with mechanical allodynia. Perspective: Whether decreased voluntary running is dependent on inflammation site is unknown. We show that intraplantar, but not L1 dorsum, CFA suppressed voluntary running and formalin-induced licking/writhing/flinching behavior but had no effect on voluntary running. These data suggest that suppressed voluntary running by CFA likely reflects pain evoked by use of the affected limbs. (C) 2014 by the American Pain Society