星形胶质细胞内三羧酸循环在福尔马林诱导的大鼠脊髓中枢敏化中的作用

The relation between krebs cycle of astrocytes and central sensitization in rats induced by formalin

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。

Objective： To investigate the function of Krebs cycle of astrocytes in acute injury,chronic persistent injury and central sensitization of the spinal cord induced by formalin. Methods： This study was performed in inflammatory pain model of rat through injecting formalin（ 5%,0. 05 ml） in the plantar of right hind,and then the behavior changes in rats were observed after intrathecal injection of 100 nmol / ml fluorocitrate（ FC） and（ or） 5 × 10^4 nmol / ml L-glutamate（ Glu）. Results：（ 1） Compared with the control group,in the acute phase： the spontaneous nociceptive behavior（ licking / biting and flinches） was inhibited by intrathecal injection of FC,which was reversed by injection of Glu;（ 2） In chronic phase： compared with the control group,single injection with FC intrathecally（ at 20 min before formalin injec-tion） significantly increased the ipsilateral mechanical threshold in 2 days（ P〈0. 01,P〈0. 05）,but increased the contralateral mechanical hyperalgesia in 1 day（ P〈0. 05）; multiple injections with FC intrathecally（ at 20 min before formalin injection and in 1 day,2 day for 3 days after formalin injection） significantly inhibited the ipsilateral mechanical hyperalgesia in 3-7 days（ P〈0. 01,P〈0. 05）,and contralateral mechanical hyperalgesia in 2-7 days（ P〈0. 01,P〈0. 05）; compared with the control group,single injection with FC intrathecally（ in 9 days after formalin injection） significantly inhabited the ipsilateral mechanical hyperalgesia and contralateral mechanical hyperalgesia at third hour（ P〈0. 05）,but the mechanical hyperalgesia recovered at six hour; multiple injections with FC intrathecally（ in 9,10,11 days after formalin injection） transiently inhibited the bilateral mechanical hyperalgesia at third hour. Conclusion： The Krebs cycle in astrocytes is involved in the formation of central sensitization in the spinal cord induced by formalin,but d not play a leading role in the maintenance of central sensitization in the spinal cord of rats.