Kandasamy Ram, Calsbeek Jonas J, Morgan Michael M
Graduate Program in Neuroscience, Washington State University, Pullman, WA, United States.
Department of Psychology, Washington State University Vancouver, Vancouver, WA, United States.
J Neurosci Methods. 2016 Apr 1;263:115-22. doi: 10.1016/j.jneumeth.2016.02.013. Epub 2016 Feb 15.
The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior.
The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats.
Injection of Complete Freund's Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in male and female rats. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test).
Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception.
The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men.
临床前研究中伤害感受的评估正在经历从疼痛诱发试验到疼痛抑制试验的转变,以更紧密地模拟临床疼痛的影响。许多炎症性疼痛抑制行为(寻求奖励、运动)已被研究,但由于压力等混杂因素以及行为量化困难,这些试验存在局限性。
本研究评估笼内转轮运动作为一种客观方法,用于评估雄性和雌性大鼠炎症性疼痛的程度和持续时间。
向右侧后爪注射完全弗氏佐剂(CFA)以诱发炎症性疼痛,几乎完全抑制了雄性和雌性大鼠2天的转轮运动。尽管存在持续的机械性超敏反应(von Frey试验),转轮运动在12天内逐渐恢复到基线水平。
持续监测笼内转轮运动改进了以往对炎症性疼痛抑制转轮运动的研究,因为它对有害刺激更敏感,避免了将大鼠从笼中取出进行测试的压力,并提供了对伤害感受变化时间进程的完整分析。
目前的数据表明,笼内转轮运动是评估大鼠炎症性疼痛的一种与临床相关的方法。炎症性疼痛引起的活动减少以及随后的逐渐恢复模拟了人类疼痛引起的活动变化。雌性大鼠疼痛抑制转轮运动比雄性大鼠更明显的趋势与女性比男性患慢性疼痛风险更高的趋势一致。