Depression of home cage wheel running reveals greater spontaneous morphine withdrawal in rats with persistent pain compared to naïve controls

Abstract

The widespread use of opioids to treat pain has led to a drastic increase in opioid dependence and overdose fatalities. The transition from the use of opioids to treat pain to abuse is driven in part by withdrawal symptoms associated with the abrupt use of opioids. The objective of the present study is to develop an animal model of withdrawal that mimics the spontaneous withdrawal that occurs in pain patients. We hypothesized that spontaneous opioid withdrawal will cause depression of home cage wheel running. This hypothesis was tested by measuring home cage wheel running before and after subcutaneous implantation of two 75 mg morphine or placebo pellets into male Sprague‐Dawley rats with and without hindpaw inflammation. Administration of the morphine pellets depressed wheel running that recovered to baseline levels by the third day after implantation in naïve rats and by the fifth day after implantation in inflamed rats. Removal of the morphine pellets depressed wheel running for 2 days in naïve animals and over 6 days in rats with an inflamed paw. These data demonstrate that home cage wheel running is a consistent and reliable method to assess spontaneous morphine withdrawal in the rat. Moreover, the magnitude of withdrawal is greatly enhanced in rats with persistent pain.Support or Funding InformationThis study was supported in part by State of Washington Initiative Measure No. 171 (to ATL) and NIH grant NS095097 (to MMM).