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目的:探讨星形胶质细胞内的三羧酸循环在福尔马林诱导的大鼠炎性持续性痛、慢性痛和脊髓中枢敏化中的作用。方法:在大鼠右后肢足底注射福尔马林(5%,0.05 ml)制备炎性持续性痛大鼠模型,鞘内注射100 nmol/ml氟代柠檬酸(fluorocitrate,FC)和/或5×104nmol/ml谷氨酸(L-glutamate,Glu)后,观察大鼠的行为学变化。结果:(1)急性期:与对照组相比,鞘内注射FC对大鼠自发伤害性行为(舔咬爪和缩腿反射)有抑制作用,而鞘内注射了Glu部分翻转了该抑制效应;(2)在慢性期,与对照组相比较,单次鞘内注射FC在3 h~2 d的时间点上显著提高大鼠同侧的50%爪缩阈值(P<0.01,P<0.05),而对侧50%爪缩阈值仅在第1 d时间点显示提高(P<0.05)。随后在福尔马林注射后第9 d,再次鞘内注射FC,与对照组相比,能在3 h提高大鼠的同侧和对侧的50%爪缩阈值(P<0.05),而在6 h阈值恢复到对照组水平(P>0.05)。多次鞘内注射FC后,能够在3~7 d时间点上显著提高大鼠同侧的50%爪缩阈值(P<0.01,P<0.05),在2~7 d时间点上显著提高大鼠对侧的50%爪缩阈值(P<0.01,P<0.05)。随后在福尔马林注射后第9、10、11 d连续3 d鞘内注射FC,大鼠同侧的50%爪缩阈值的提高仅在鞘内注射日当天发生(P<0.01,P<0.05),次日即恢复到对照组水平(P>0.05),而对侧的50%爪缩阈值在鞘内注射日第11 d及第12 d有所提高(P<0.05),第13 d恢复到对照组水平(P>0.05)。结论:星形胶质细胞内的三羧酸循环参与福尔马林诱导的急性痛和慢性痛的形成,但是在慢性痛的维持方面不起主导作用。
AIM: To investigate the role of tricarboxylic acid cycle in astrocytes in formalin-induced inflammatory persistent pain, chronic pain and spinal sensitization in rats. Methods: The rat model of inflammatory persistent pain was established by injecting formalin (5%, 0.05 ml) into the plantar of the right posterior limb of rats, and intrathecally injected with 100 nmol / ml fluorocitrate (FC) and / or 5 × 104nmol / ml glutamate (L-glutamate, Glu), observe the behavioral changes in rats. Results: (1) Acute phase: intrathecal injection of FC had inhibitory effect on spontaneous nociceptive behavior (lick bite paw and contracted leg reflex) in rats compared with control group, whereas intrathecal injection of Glu partially reversed this inhibitory effect ; (2) Compared with the control group, intrathecal intrathecal injection of FC significantly increased the ipsilateral 50% paw withdrawal threshold (P <0.05) at 3 h to 2 d in chronic phase ), Whereas contralateral 50% paw withdrawal threshold showed an increase only at day 1 (P <0.05). Subsequent intrathecal injection of FC on day 9 after formalin injection increased the 50% paw withdrawal threshold (P <0.05) at 3 h in both ipsilateral and contralateral rats compared with the control group, whereas The threshold returned to control level at 6 h (P> 0.05). Repeated intrathecal injection of FC significantly increased the ipsilateral 50% paw withdrawal threshold (P <0.01, P <0.05) at 3 to 7 days and increased significantly at 2 to 7 days 50% paw withdrawal contralateral threshold (P <0.01, P <0.05). Subsequent intrathecal injection of FC on the 9th, 10th, and 11th day after formalin injection increased the 50% paw withdrawal threshold of the ipsilateral rats only on the day of intrathecal injection (P <0.01, P < 0.05), and returned to control level on the next day (P> 0.05), while contralateral 50% paw withdrawal threshold increased on the 11th and 12th day after intrathecal injection (P <0.05) Returned to the control group (P> 0.05). CONCLUSION: The tricarboxylic acid cycle in astrocytes is involved in the formation of formalin-induced acute pain and chronic pain, but does not play a dominant role in the maintenance of chronic pain.