Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats
Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats
复制标题
DOI：
10.1038/sj.npp.1300315
复制
发表时间：
2004-02-01
影响因子：
7.6
通讯作者：
DeLeo, JA
中科院分区：
文献类型：
--
作者：
Raghavendra, V;Tanga, FY;DeLeo, JA
脊髓神经胶质细胞的激活和促炎细胞因子的表达增强与吗啡耐受和吗啡戒断引起的痛觉过敏的发生有关。本研究观察了神经胶质调节剂丙戊茶碱对慢性吗啡处理大鼠镇痛耐受和戒断痛过敏表达的影响。重复皮下注射吗啡慢性给药可诱导腰髓神经胶质细胞活化和促炎细胞因子水平升高。此外，神经胶质细胞的激活和促炎细胞因子水平的升高与吗啡耐受和痛觉过敏的表达存在时间相关性。一直以来，丙戊茶碱减轻了痛觉过敏的发展和脊髓对吗啡的止痛耐受性。在吗啡耐受诱导过程中给予丙戊茶碱也可减弱1.5腰髓神经胶质细胞的激活和促炎细胞因子。这些结果进一步支持了脊髓胶质细胞和促炎细胞因子参与了吗啡耐受和相关的异常疼痛敏感性机制的假说。
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 1.5 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.