D2 Receptors in the Periaqueductal Gray/Dorsal Raphe Modulate Peripheral Inflammatory Hyperalgesia via the Rostral Ventral Medulla.
D2 Receptors in the Periaqueductal Gray/Dorsal Raphe Modulate Peripheral Inflammatory Hyperalgesia via the Rostral Ventral Medulla.
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中脑导水管周围灰质/中缝背侧D2受体通过延髓头端调节外周炎性痛觉过敏
DOI：
10.1016/j.neuroscience.2021.03.035
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发表时间：
2021-05-21
期刊：
影响因子：
3.3
通讯作者：
Taylor NE
中科院分区：
文献类型：
--
作者：
Ferrari LF;Pei J;Zickella M;Rey C;Zickella J;Ramirez A;Taylor NE
中脑导水管周围灰质（PAG）/中缝背核中的多巴胺神经元是具有已知脊髓上靶点的抗伤害感受的关键调节器。然而，没有研究直接测试这些神经元是否有助于下行疼痛抑制。我们假设PAG多巴胺神经元通过延髓头端腹侧区（RVM）的下行调节机制参与D-苯丙胺的镇痛作用。雄性C57 BL/6小鼠在接受D-苯丙胺全身注射后，PAG多巴胺神经元中的c-FOS表达增加，并且对热刺激的缩爪潜伏期显著增加。有针对性的微量输注D-安非他明，左旋多巴，或选择性D2激动剂quinpirole到PAG产生镇痛，而D1激动剂，氯APB，没有效果。此外，依替氯必利对PAG中D2受体的抑制阻止了系统性D-苯丙胺镇痛作用。RVM内注射利多卡因或GABAA受体激动剂蝇蕈醇可抑制D-苯丙胺和PAG D2受体介导的镇痛作用，表明该镇痛模型中存在PAG-RVM信号通路。最后，无论是全身D-苯丙胺和局部PAG微量注射喹吡罗，抑制角叉菜胶诱导的炎性痛敏。PAG内注射依替氯必利以及RVM微量注射蝇蕈醇可短暂恢复这种痛觉过敏。我们的结论是，D-苯丙胺镇痛部分介导的下行抑制和D2受体的PAG负责通过调节神经元，项目的RVM的这种效果。这些结果进一步加深了我们对多巴胺的抗伤害效应的理解，并阐明了临床上可用的多巴胺调节剂产生镇痛作用的机制。
Dopamine neurons in the periaqueductal gray (PAG)/dorsal raphe are key modulators of antinociception with known supraspinal targets. However, no study has directly tested whether these neurons contribute to descending pain inhibition. We hypothesized that PAG dopamine neurons contribute to the analgesic effect of D-amphetamine via a mechanism that involves descending modulation via the rostral ventral medulla (RVM). Male C57BL/6 mice showed increased c-FOS expression in PAG dopamine neurons and a significant increase in paw withdrawal latency to thermal stimulation after receiving a systemic injection of D-amphetamine. Targeted microinfusion of D-amphetamine, L-DOPA, or the selective D2 agonist quinpirole into the PAG produced analgesia, while a D1 agonist, chloro APB, had no effect. In addition, inhibition of D2 receptors in the PAG by eticlopride prevented the systemic D-amphetamine analgesic effect. D-amphetamine and PAG D2 receptor-mediated analgesia were inhibited by intra-RVM injection of lidocaine or the GABAA receptor agonist muscimol, indicating a PAG-RVM signaling pathway in this model of analgesia. Finally, both systemic D-amphetamine and local PAG microinjection of quinpirole, inhibited inflammatory hyperalgesia induced by carrageenan. This hyperalgesia was transiently restored by intra-PAG injection of eticlopride, as well as RVM microinjection of muscimol. We conclude that D-amphetamine analgesia is partially mediated by descending inhibition and that D2 receptors in the PAG are responsible for this effect via modulating neurons that project to the RVM. These results further our understanding of the antinociceptive effects of dopamine and elucidate a mechanism by which clinically available dopamine modulators produce analgesia.
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影响因子：
158.5
作者：
FORREST, WH;BROWN, BW;TEUTSCH, G
通讯作者：
TEUTSCH, G
影响因子：
3.4
作者：
Covey, Dan P.;Bunner, Kendra D.;Garris, Paul A.
通讯作者：
Garris, Paul A.
DOI：
10.1177/0269881113482532
发表时间：
2013-06
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Heal DJ;Smith SL;Gosden J;Nutt DJ
通讯作者：
Nutt DJ
影响因子：
5
作者：
Chen, QiLiang;Heinricher, Mary M.
通讯作者：
Heinricher, Mary M.
影响因子：
5.5
作者：
Bannister, Kirsty;Dickenson, A. H.
通讯作者：
Dickenson, A. H.