Opioid-mediated Pain Sensitivity in Mice Bred for High Voluntary Wheel Running

We tested the hypothesis that thermal tail-flick latency, a common measure of pain sensitivity in rodents, would be altered in lines of mice that had been selectively bred for high voluntary wheel-running behavior. Specifically, we predicted that the selected (High-Runner) lines would show decreased pain sensitivity relative to their control (C; randombred) lines, and would respond differently to drugs that block opioid receptors. We first compared tail-flick latency between High-Runner and C female mice during the day (no wheel access) and at night (with wheel access). Second, we compared effects of the opioid antagonist naloxone (10 mg/kg, i.p.) on tail-flick latency during the day (no wheel access). Third, we compared effects of naloxone (5 and 10 mg/kg, i.p.) and naltrexone, a longer-lasting opioid antagonist (0.1, 1, 5, 10, 50, and 100 mg/kg, i.p.), on voluntary wheel running. Tail-flick latencies were longer at night (when mice were active on wheels), but mice from High-Runner and C lines did not differ during the day or night. Administration of naloxone (10 mg/kg, i.p.) decreased tail-flick latency measured during the day, equally in High-Runner and C mice. Naloxone (5 and 10 mg/kg, i.p.) and high doses of naltrexone (50 and 100 mg/kg, i.p.) decreased wheel running equally in High-Runner and C mice. Further studies will be required to determine whether other types of pain sensitivity have also failed to evolve in association with increased voluntary wheel running.