title: Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function.
abstract: Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund's Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50dose of morphine (3.2mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients.
authors.affiliation: Graduate Program in Neuroscience, Washington State University, Pullman, WA, United States. Electronic address: ram_kandasamy@wsu.edu.
authors.forename: Ram
authors.initials: R
authors.lastname: Kandasamy
authors.affiliation: Department of Psychology, Washington State University Vancouver, Vancouver, WA, United States.
authors.forename: Jonas J
authors.initials: JJ
authors.lastname: Calsbeek
authors.affiliation: Graduate Program in Neuroscience, Washington State University, Pullman, WA, United States; Department of Psychology, Washington State University Vancouver, Vancouver, WA, United States.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Morgan
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D002047:Buprenorphine / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008297:Male; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D012420:Running / Q000502:physiology*; D012737:Sex Factors
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D005620:Freund's Adjuvant
keywords: Antinociception; Buprenorphine; Morphine; Pain-depressed behavior; Sex differences