Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Neuroscience. 2013 Nov 12;252:359-66. doi: 10.1016/j.neuroscience.2013.08.030. Epub 2013 Aug 28.
Pain has sensory-discriminative and emotional-affective dimensions. Recent studies show that the affective component can be assessed with a conditioned place avoidance (CPA) test. We hypothesized that systemic morphine before a post-conditioning test would more potently attenuate the affective aspect compared to the sensory component and that [d-Ala2-N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO), a μ-selective opioid receptor agonist, injected into the central nucleus of the amygdala (CeA) would reduce established CPA. A rat model of inflammatory pain, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a CPA test. Three experiments were performed on adult male Sprague-Dawley rats. Systemic morphine (0.5 or 1.0mg/kg) in Experiment 1, intrathecal (i.t.) morphine (2.5 μg/rat) in Experiment 2, and intra-CeA DAMGO (7.7-15.4 ng/0.4 μl) in Experiment 3 were given to CFA-injected rats (n=6-8/group) prior to a post-conditioning test. Saline-injected rats were used as control. Time spent in a pain-paired compartment was recorded twice, before conditioning and after a post-conditioning test. Paw withdrawal latency (PWL) to a noxious thermal stimulus was measured before experiment at day-1 and after the post-conditioning test; hyperalgesia was defined as a decrease in PWL. The data showed that CFA-injected rats had significantly negative CPA compared to those of saline-injected rats (P<0.05). Low-dosage systemic morphine significantly (P<0.05) reduced CFA-induced CPA but had no effect on PWL. I.t. morphine did not inhibit the display of CPA but significantly increased PWL, suppressing hyperalgesia (P<0.05). Intra-CeA DAMGO significantly inhibited the display of CPA compared to saline (P<0.05) but had no effect on PWL. The data demonstrate that morphine attenuates the affective component more powerfully than it does the sensory and suggests that the sensory and the emotional-affective dimensions are underpinned by different mechanisms.
疼痛具有感觉辨别和情感影响两个维度。最近的研究表明，情感成分可以通过条件位置回避（CPA）测试进行评估。我们假设，在条件后测试前给予全身吗啡会比感觉成分更有效地减弱情感方面，并且[D-Ala2-N-Me-Phe4，Gly-ol5]-脑啡肽（DAMGO），一种μ选择性阿片受体激动剂，注入杏仁核中央核（CeA）会减少已建立的 CPA。通过向后爪注射完全弗氏佐剂（CFA）建立大鼠炎症性疼痛模型，与 CPA 测试相结合。在成年雄性 Sprague-Dawley 大鼠上进行了三项实验。在实验 1 中给予全身吗啡（0.5 或 1.0mg/kg），在实验 2 中给予鞘内（i.t.）吗啡（2.5μg/大鼠），在实验 3 中给予 CeA 内 DAMGO（7.7-15.4ng/0.4μl），在条件后测试前给予 CFA 注射大鼠（每组 6-8 只）。盐水注射大鼠作为对照。在实验前一天和条件后测试后，两次记录疼痛配对室中的时间。测量对有害热刺激的爪退缩潜伏期（PWL）。实验前在第 1 天和条件后测试后测量 PWL；痛觉过敏定义为 PWL 降低。数据显示，与盐水注射大鼠相比，CFA 注射大鼠的 CPA 明显呈阴性（P<0.05）。低剂量全身吗啡显著（P<0.05）降低 CFA 诱导的 CPA，但对 PWL 无影响。i.t. 吗啡不抑制 CPA 的表现，但显著增加 PWL，抑制痛觉过敏（P<0.05）。与盐水相比，CeA 内 DAMGO 显著抑制 CPA 的表现（P<0.05），但对 PWL 无影响。数据表明，吗啡对情感成分的减弱作用比感觉成分更强，表明感觉和情感影响维度由不同的机制支撑。
