Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala
Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala
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DOI：
10.1038/sj.npp.1300858
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发表时间：
2006-04-01
影响因子：
7.6
通讯作者：
Suzuki, T
中科院分区：
文献类型：
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作者：
Narita, M;Kaneko, C;Suzuki, T
临床上，有报道称慢性疼痛会导致抑郁、焦虑和生活质量下降。内源性阿片系统与痛觉、焦虑和压力有关。本研究旨在探讨慢性疼痛是否能诱导小鼠杏仁核的焦虑效应和阿片能功能的变化。我们发现，注射完全弗氏佐剂（CFA）或坐骨神经结扎引起的神经性疼痛在注射或手术后4周均产生显著的焦虑作用。在这些条件下，选择性阿片受体激动剂[D-Ala(2), N-MePhe(4), Gly(5)-ol]-脑啡肽（DAMGO）和选择性阿片受体激动剂(+)-4-[(α R)- α -（(2S, 5R)-4-烯丙基-2,5-二甲基-1-哌嗪基）-3-甲氧基苄基]- n， n -二乙基苯酰胺（SNC80）]刺激[S-35] GTP γ S在杏仁核膜上的结合被CFA注射或神经结扎显著抑制。CFA注射与kappa-阿片受体激动剂2-（3,4-二氯苯基）- n -甲基- n -[(1S)-1-苯基-2-（1-吡啶基）乙基]盐酸乙酰胺(ICI199,441)-刺激[S-35] GTP γ S在杏仁核膜上的结合显著增加相关。选择性mu-阿片受体拮抗剂、选择性delta-阿片受体拮抗剂和内源性kappa-阿片受体配体dynorphin a在小鼠脑室内给药和微注射可引起显著的焦虑效应。我们还发现，术后8周，坐骨神经结扎引起的热痛觉过敏得到逆转。在明暗试验中，术后8周在亮室中度过的时间没有改变。总的来说，目前的数据构成了慢性疼痛在小鼠中具有焦虑效应的第一个证据。这种现象可能与杏仁核中阿片能功能的改变有关。
Clinically, it has been reported that chronic pain induces depression, anxiety, and reduced quality of life. The endogenous opioid system has been implicated in nociception, anxiety, and stress. The present study was undertaken to investigate whether chronic pain could induce anxiogenic effects and changes in the opioidergic function in the amygdala in mice. We found that either injection of complete Freund's adjuvant (CFA) or neuropathic pain induced by sciatic nerve ligation produced a significant anxiogenic effect at 4 weeks after the injection or surgery. Under these conditions, the selective mu-opioid receptor agonist [D-Ala(2), N-MePhe(4), Gly(5)-ol]- enkephalin (DAMGO)and the selective delta-opioid receptor agonist ( +)-4-[(alpha R)-alpha-((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80)-stimulated [S-35] GTP gamma S binding in membranes of the amygdala was significantly suppressed by CFA injection or nerve ligation. CFA injection was associated with a significant increase in the kappa-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N-[( 1S)-1-phenyl-2-(1-pyrrolidinyl) ethyl] acetamide hydrochloride ( ICI199,441)- stimulated [S-35] GTP gamma S binding in membranes of the amygdala. The intracerebroventricular administration and microinjection of a selective mu-opioid receptor antagonist, a selective delta-opioid receptor antagonist, and the endogenous kappa-opioid receptor ligand dynorphin A caused a significant anxiogenic effect in mice. We also found that thermal hyperalgesia induced by sciatic nerve ligation was reversed at 8 weeks after surgery. In the light - dark test, the time spent in the lit compartment was not changed at 8 weeks after surgery. Collectively, the present data constitute the first evidence that chronic pain has an anxiogenic effect in mice. This phenomenon may be associated with changes in opioidergic function in the amygdala.