Striatal dopamine D2 receptors attenuate neuropathic hypersensitivity in the rat
Striatal dopamine D2 receptors attenuate neuropathic hypersensitivity in the rat
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DOI：
10.1016/j.expneurol.2007.03.010
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发表时间：
2007-06-01
影响因子：
5.3
通讯作者：
Pertovaara, Antti
中科院分区：
文献类型：
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作者：
Ansah, Osei B.;Leite-Almeida, Hugo;Pertovaara, Antti
早期的研究表明，纹状体多巴胺D-2受体参与了非神经性条件下的痛觉调节。我们评估了纹状体多巴胺D-2受体是否也在神经病变条件下参与了痛觉调节。采用单侧结扎大鼠胫神经和腓总神经的方法建立大鼠备用神经损伤模型。在清醒的神经损伤动物中，纹状体注射多巴胺D-2受体激动剂奎匹罗后，对校准的单丝或有毒加热的疼痛相关撤退反应减弱。疼痛相关反应仅在注射同侧的神经损伤肢体和中线(尾部)减弱。在未手术的对照组中，纹状体注射抗过敏剂量的奎比罗并不影响对机械刺激的戒断反应。鞘内注射多巴胺D-2受体拮抗剂(替氯普利)或非选择性5-羟色胺受体拮抗剂(甲基舍吉德)可逆转由纹状体给药引起的疼痛相关反应的减弱，但不能被α(2)-肾上腺素能受体拮抗剂(阿替美唑)逆转。在轻度麻醉的神经病变动物的轮回腹侧延髓，纹状体注射喹比罗显著降低了可能由伤害性刺激激活的前伤害性感受细胞的活性。在轻度麻醉的对照动物中，纹状体注射抗过敏剂量的喹比罗并不能抑制无害的H反射。结果表明，纹状体多巴胺D-2受体可减轻神经病理性超敏反应。纹状体多巴胺D-2受体在周围神经病中的抗超敏作用包括抑制延髓轮状腹内侧区可能是伤害性感觉神经元的脉冲放电，以及对脊髓5-羟色胺和多巴胺D-2受体的下行影响。(C)2007 Elsevier Inc.保留所有权利。
Earlier studies indicate that striatal dopamine D-2 receptors are involved in pain regulation in non-neuropathic conditions. We assessed whether striatal dopamine D-2 receptors contribute to pain regulation also in neuropathic conditions. The spared nerve injury model of neuropathy was induced by unilateral ligation of the tibial and common peroneal nerves in the rat. In awake nerve-injured animals, pain-related withdrawal responses to calibrated monofilaments or noxious heating were attenuated following striatal administration of a dopamine D-2 receptor agonist quinpirole. Pain-related responses were attenuated only in the nerve-injured limb ipsilateral to the injection and in the midline (tail). In unoperated controls, striatal administration of quinpirole at an antihypersensitive dose did not influence withdrawal responses to mechanical stimulation. Attenuation of pain-related responses induced by striatal administration of quinpirole was reversed by intrathecal administration of a dopamine D-2 receptor antagonist (eticlopride) or a non-selective 5-HT receptor antagonist (methysergide), but not by an alpha(2)-adrenoceptor antagonist (atipamezole). In the rostroventromedial medulla of lightly anesthetized neuropathic animals, striatal administration of quinpirole significantly decreased the activity of presumably pronociceptive cells that are activated by noxious stimulation. The innocuous H-reflex in lightly anesthetized control animals was not suppressed by striatal administration of quinpirole at an antihypersensitive dose. The results indicate that striatal dopamine D-2 receptors attenuate neuropathic hypersensitivity. The antihypersensitive effect induced by striatal dopamine D-2 receptors in peripheral neuropathy involves suppression of impulse discharge of presumably pronociceptive neurons in the rostroventromedial medulla, and a descending influence acting on spinal 5-HT and dopamine D-2 receptors. (c) 2007 Elsevier Inc. All rights reserved.