Raghavendra Vasudeva, Tanga Flobert Y, DeLeo Joyce A
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Neuropsychopharmacology. 2004 Feb;29(2):327-34. doi: 10.1038/sj.npp.1300315.
The activation of glial cells and enhanced proinflammatory cytokine expression at the spinal cord has been implicated in the development of morphine tolerance, and morphine withdrawal-induced hyperalgesia. The present study investigated the effect of propentofylline, a glial modulator, on the expression of analgesic tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced glial activation and enhanced proinflammatory cytokine levels at the lumbar spinal cord. Moreover, glial activation and enhanced proinflammatory cytokine levels exhibited a temporal correlation with the expression of morphine tolerance and hyperalgesia. Consistently, propentofylline attenuated the development of hyperalgesia and the expression of spinal analgesic tolerance to morphine. The administration of propentofylline during the induction of morphine tolerance also attenuated glial activation and proinflammatory cytokines at the L5 lumbar spinal cord. These results further support the hypothesis that spinal glia and proinflammatory cytokines contribute to the mechanisms of morphine tolerance and associated abnormal pain sensitivity.
脊髓中胶质细胞的激活以及促炎细胞因子表达的增强与吗啡耐受性的发展和吗啡戒断诱导的痛觉过敏有关。本研究调查了胶质调节剂丙戊茶碱对慢性吗啡处理大鼠镇痛耐受性表达和戒断诱导痛觉过敏的影响。通过反复皮下注射进行慢性吗啡给药可诱导胶质细胞激活，并提高腰段脊髓促炎细胞因子水平。此外，胶质细胞激活和促炎细胞因子水平的提高与吗啡耐受性和痛觉过敏的表达呈现出时间相关性。同样，丙戊茶碱减弱了痛觉过敏的发展以及对吗啡的脊髓镇痛耐受性的表达。在诱导吗啡耐受性期间给予丙戊茶碱也减弱了L5腰段脊髓的胶质细胞激活和促炎细胞因子。这些结果进一步支持了以下假设：脊髓胶质细胞和促炎细胞因子促成了吗啡耐受性及相关异常疼痛敏感性的机制。
