Analysis of Formalin‐depressed Wheel Running and its Reversal by Ketoprofen

Abstract

Traditional pain-evoked tests (e.g., hot plate and tail withdrawal tests) do not mimic the disruptive effects of pain on daily life, a primary outcome measure used for pain in humans. To solve this problem, we demonstrated that pain-depressed home cage wheel running is an objective and clinically relevant measure of the functional consequences of chronic inflammatory pain in the rat. However, few studies have examined the functional consequences of acute pain; thus, the aim of this study was to examine the effects of acute formalin-induced inflammatory pain on function as measured by home cage wheel running. Rats were housed in individual cages containing a computerized running wheel. Rats were allowed free access to the wheel 23 hours/day for 7 days prior to the induction of hindpaw inflammation to acquire stable running levels. Wheel running during the 23 hours immediately prior to induction of inflammation was used as the baseline. Inflammation was induced with an intraplantar injection of formalin (5%, 0.05 mL) into the right hindpaw. The functional effects of a single formalin injection were apparent as indicated by decreased wheel running after the first hour following injection. Interestingly, wheel running also decreased in the 7th hour following formalin injection. In the 7th hour, wheel running was depressed in the absence of mechanical allodynia and spontaneous pain behaviors, suggesting that pain-evoked behaviors and decreased function are independent of each other. A pretreatment of the nonsteroidal anti-inflammatory drug ketoprofen (10 mg/kg) prevented depression of wheel running in both the 1st and 7th hour. These results indicate that continuous monitoring of the functional consequences of pain using home cage wheel running reveal insights into long-term changes in behavior resulting from acute pain, and that early treatment may prevent functional deficits due to acute pain.