Ansah Osei B, Leite-Almeida Hugo, Wei Hong, Pertovaara Antti
Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, University of Helsinki, 00014 Helsinki, Finland.
Exp Neurol. 2007 Jun;205(2):536-46. doi: 10.1016/j.expneurol.2007.03.010. Epub 2007 Mar 21.
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.
早期研究表明，纹状体多巴胺D(2)受体参与非神经病理性疼痛的调节。我们评估了纹状体多巴胺D(2)受体是否也在神经病理性疼痛中发挥疼痛调节作用。通过单侧结扎大鼠胫神经和腓总神经建立神经病理性损伤的 spared nerve injury模型。在清醒的神经损伤动物中，纹状体注射多巴胺D(2)受体激动剂喹吡罗后，对校准单丝或有害热刺激的疼痛相关退缩反应减弱。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。在未手术的对照动物中，以抗超敏剂量纹状体注射喹吡罗不影响对机械刺激的退缩反应。鞘内注射多巴胺D(2)受体拮抗剂（依替必利）或非选择性5-羟色胺受体拮抗剂（甲基麦角新碱）可逆转纹状体注射喹吡罗引起的疼痛相关反应减弱，但α(2)-肾上腺素能受体拮抗剂（阿替哌唑）则不能。在轻度麻醉的神经病理性动物的延髓头端腹内侧，纹状体注射喹吡罗显著降低了可能被有害刺激激活的伤害性感受细胞的活性。在轻度麻醉的对照动物中，以抗超敏剂量纹状体注射喹吡罗不会抑制无害的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。外周神经病变中纹状体多巴胺D(2)受体诱导的抗超敏作用涉及抑制延髓头端腹内侧可能的伤害性感受神经元的冲动发放，以及对脊髓5-羟色胺和多巴胺D(2)受体的下行影响。
