Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy (Retracted article. See vol. 30, pg. 2235, 2009)
Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy (Retracted article. See vol. 30, pg. 2235, 2009)
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DOI：
10.1111/j.1460-9568.2008.06425.x
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发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Levine, Jon D.
中科院分区：
文献类型：
--
作者：
Dina, Olayinka A.;Khasar, Sachia G.;Levine, Jon D.
儿茶酚胺代谢物的神经毒性作用与神经退行性疾病有关。由于一些感觉神经元表达酪氨酸羟化酶和单胺氧化酶（MAO），我们在酒精性神经病模型中研究了儿茶酚胺代谢物对神经性疼痛的潜在贡献。感觉神经元中儿茶酚胺的存在是由辣椒素刺激的肾上腺素释放支持的，这种作用在乙醇喂养的大鼠中得到加强。新生儿服用辣椒素后，背根神经节中参与儿茶酚胺摄取和代谢的酶、多巴胺β -羟化酶和MAO-A的mRNA表达降低。通过全身和局部外周给药MAO-A抑制剂、感觉神经元中去甲肾上腺素转运蛋白（NET）的减少和NET抑制剂，可以减轻乙醇引起的痛觉过敏。最后，皮内注射3,4-二羟基苯基乙醇醛（DOPEGAL），一种神经毒性MAO-A儿茶酚胺代谢物，产生强烈的机械痛觉过敏。这些观察结果表明，伤害感受器中的儿茶酚胺被MAO-A代谢为神经毒性产物，这可能导致神经性疼痛的神经功能障碍。
The neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. As some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO), we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin-stimulated epinephrine release, an effect enhanced in ethanol-fed rats. mRNA for enzymes in dorsal root ganglia involved in catecholamine uptake and metabolism, dopamine beta-hydroxylase and MAO-A, were decreased by neonatal administration of capsaicin. Ethanol-induced hyperalgesia was attenuated by systemic and local peripheral administration of inhibitors of MAO-A, reduction of norepinephrine transporter (NET) in sensory neurons and a NET inhibitor. Finally, intradermal injection of 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), a neurotoxic MAO-A catecholamine metabolite, produced robust mechanical hyperalgesia. These observations suggest that catecholamines in nociceptors are metabolized to neurotoxic products by MAO-A, which can cause neuronal dysfunction underlying neuropathic pain.