Journal article
Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function
Behavioural brain research, Vol.317, pp.502-507
01/15/2017
Handle:
https://hdl.handle.net/2376/101714
PMCID: PMC5107346
PMID: 27746208
Abstract
•Home cage wheel running can be used to assess pain and opioid analgesia.•Low doses of morphine reversed pain-depressed wheel running only.•High doses of morphine reversed evoked hypersensitivity only.•All buprenorphine doses depressed wheel running in all rats.•Wheel running reveals limitations of opioids to restore normal activity.
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 ED50 dose 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.
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Details
- Title
- Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function
- Creators
- Ram Kandasamy - Graduate Program in Neuroscience, Washington State University, Pullman, WA, United StatesJonas J Calsbeek - Department of Psychology, Washington State University Vancouver, Vancouver, WA, United StatesMichael M Morgan - Graduate Program in Neuroscience, Washington State University, Pullman, WA, United States
- Publication Details
- Behavioural brain research, Vol.317, pp.502-507
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier B.V
- Identifiers
- 99900546637701842
- Language
- English
- Resource Type
- Journal article