Cahill C M, Dray A, Coderre T J
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, 110 Pine Ave. West, Montreal, Canada.
Brain Res. 1998 Oct 12;808(1):13-22. doi: 10.1016/s0006-8993(98)00786-0.
Central inflammation is an integral component and contributor of the pathology of many debilitating diseases and has been shown to produce spontaneous pain and hyperalgesia. Recently, administration of lipopolysaccharide (LPS) into the lateral ventricle of rats was shown to elicit both thermal hyperalgesia and tactile allodynia [K. Walker, A. Dray, M. Perkins, Hyperalgesia in rats following intracerebroventricular administration of endotoxin: effect of bradykinin B1 and B2 receptor antagonist treatment, Pain 65 (1996) 211-219]. In this study, we have replicated the LPS model with some adaptations and correlated the nociceptive behaviors with an increased expression of activated macrophages in the central nervous system. We also examined the effects of priming on LPS-induced decreases in thermal nociceptive thresholds and mechanical response thresholds following either central or peripheral administration. Intracerebroventricular (i.c.v.) administration of LPS (0.2 microgram/rat) did not alter either thermal (hot plate) or mechanical (von Frey filaments) thresholds compared to baseline values in the first few hours after injection. However, priming rats by pretreating with i.c.v. LPS (0.2 microgram) 24 h prior to testing with i.c.v. LPS (0.2 microgram) produced significant mechanical allodynia and thermal hyperalgesia. The mechanical allodynia had an onset of 80 min after injection and a duration of 5 h. A similar time course was observed for thermal hyperalgesia, although its expression was less pronounced. Immunohistochemical studies indicated an increased expression of activated macrophages in the brain parenchyma of primed rats but not in unprimed rats. Intraperitoneal (i.p., 2 mg/kg) administration of LPS had no significant effect on either thermal or mechanical thresholds in the first few hours after injection; however, priming rats via i.p. (0.2 mg/kg) or i.c.v. (0.2 microgram) LPS produced a reduction in both thermal nociceptive thresholds and mechanical response thresholds in rats given a subsequent i.p. injection of LPS. This study demonstrates that priming is an effective protocol for the induction of central inflammation and increases the duration of these behaviors after i.c. v. administration.
中枢炎症是许多使人衰弱疾病病理过程中不可或缺的组成部分和促成因素，并且已被证明会引发自发性疼痛和痛觉过敏。最近，向大鼠侧脑室注射脂多糖（LPS）被证明会引发热痛觉过敏和触觉异常性疼痛[K. 沃克、A. 德雷、M. 珀金斯，脑室内注射内毒素后大鼠的痛觉过敏：缓激肽B1和B2受体拮抗剂治疗的影响，《疼痛》65（1996年）211 - 219]。在本研究中，我们对LPS模型进行了一些改进并进行了复制，将伤害性感受行为与中枢神经系统中活化巨噬细胞表达的增加相关联。我们还研究了预处理对中枢或外周给予LPS后热痛觉阈值和机械反应阈值降低的影响。与注射后最初几个小时的基线值相比，脑室内（i.c.v.）注射LPS（0.2微克/只大鼠）并未改变热（热板）或机械（von Frey细丝）阈值。然而，在进行脑室内注射LPS（0.2微克）测试前24小时，通过脑室内预处理LPS（0.2微克）对大鼠进行预处理，会产生显著的机械性异常性疼痛和热痛觉过敏。机械性异常性疼痛在注射后80分钟开始出现，持续时间为5小时。热痛觉过敏也观察到类似的时间进程，尽管其表现不太明显。免疫组织化学研究表明，预处理大鼠脑实质中活化巨噬细胞的表达增加，而未预处理大鼠则没有。腹腔内（i.p.，2毫克/千克）注射LPS在注射后的最初几个小时对热或机械阈值均无显著影响；然而，通过腹腔内（0.2毫克/千克）或脑室内（0.2微克）LPS对大鼠进行预处理，会使随后腹腔内注射LPS的大鼠的热痛觉阈值和机械反应阈值均降低。本研究表明，预处理是诱导中枢炎症的有效方案，并且会增加脑室内给药后这些行为的持续时间。
