Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and spinal glia
Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and spinal glia
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DOI：
10.1016/j.bbr.2004.05.006
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发表时间：
2005-01-06
影响因子：
2.7
通讯作者：
Westbrook, RF
中科院分区：
文献类型：
--
作者：
Johnston, IN;Westbrook, RF
腹膜腔内(Ip)注射毒素，如细菌内毒素脂多糖(LPS)，与对疼痛刺激(痛觉过敏)的敏感性增加有关[Watkins LR，Maier SF，Goehler Le]。免疫激活：促炎细胞因子在炎症、疾病反应和病理性疼痛状态中的作用。Pain 1995；63：289-302。[53]当疼痛敏感度恢复到基础水平时，阿片类止痛剂(抗痛)会更持久地减少[Johnston IN，Westbrook RE急性和条件性疾病减少吗啡止痛。《大脑行为》2003；142：89-97]。在这里，我们表明，这种抑制吗啡镇痛24小时后，单次腹腔注射。注射脂多糖涉及促进疾病引起的痛敏和对吗啡的止痛耐受性发展的机制。具体地说，如果在LPS之前全身注射非竞争性NMDA受体拮抗剂(MK-801)、脊髓注射胶质代谢抑制剂(氟柠檬酸盐)或脑室内微量注射阿片受体拮抗剂(纳洛酮)，则吗啡的镇痛作用可以恢复。内毒素后注射MK-801可恢复吗啡的镇痛作用。这些结果表明，内毒素招募的机制与阿片类药物给药后降低吗啡耐受性的机制相似，如果不是相同的话：即刺激阿片和NMDA受体以及招募脊髓胶质细胞。(C)2004爱思唯尔B.V.保留所有权利。
Intraperitoneal (i.p.) injection of toxins, such as the bacterial endotoxin lipopolysaccharide (LPS), is associated with a well-characterized increase in sensitivity to painful stimuli (hyperalgesia) [Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 1995;63:289-302. [53]] and a longer-lasting reduction in opioid analgesia (anti-analgesia) when pain sensitivity returns to basal levels [Johnston IN, Westbrook RE Acute and conditioned sickness reduces morphine analgesia. Behav Brain Res 2003; 142:89-97]. Here we show that this inhibition of morphine analgesia 24 It after a single i.p. injection of LPS involves mechanisms that contribute to illness-induced hyperalgesia and the development of analgesic tolerance to morphine. Specifically, morphine analgesia was restored if LPS was preceded by systemic administration of a non-competitive NMDA receptor antagonist (MK-801), spinal infusion of a glial metabolic inhibitor (fluorocitrate), or intracerebroventricular microinjection of an opioid receptor antagonist (naloxone). Morphine analgesia was also restored if MK-801 was administered after LPS. These results demonstrate that LPS recruits similar, if not the same mechanisms that reduce morphine tolerance following opiate administration: namely, stimulation of opioid and NMDA receptors and recruitment of spinal glia. (C) 2004 Elsevier B.V. All rights reserved.