The dopamine D1?D2DR complex in the rat spinal cord promotes neuropathic pain by increasing neuronal excitability after chronic constriction injury

Bao Yi-Ni; Dai Wen-Ling; Fan Ji-Fa; Ma Bin; Li Shan-Shan; Zhao Wan-Li; Yu Bo-Yang; Liu Ji-Hua

doi:10.1038/s12276-021-00563-5

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자료유형: 학술저널

저자정보: Bao Yi-Ni (China Pharmaceutical University) Dai Wen-Ling (China Pharmaceutical University) Fan Ji-Fa (China Pharmaceutical University) Ma Bin (China Pharmaceutical University) Li Shan-Shan (China Pharmaceutical University) Zhao Wan-Li (China Pharmaceutical University) Yu Bo-Yang (China Pharmaceutical University) Liu Ji-Hua (China Pharmaceutical University)

저널정보: 대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제53권

발행연도: 2021.2

수록면: 1 - 15 (15page)

DOI: 10.1038/s12276-021-00563-5

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Dopamine D1 receptor (D1DR) and D2 receptor (D2DR) are closely associated with pain modulation, but their exact effects on neuropathic pain and the underlying mechanisms remain to be identified. Our research revealed that intrathecal administration of D1DR and D2DR antagonists inhibited D1?D2DR complex formation and ameliorated mechanical and thermal hypersensitivity in chronic constriction injury (CCI) rats. The D1?D2DR complex was formed in the rat spinal cord, and the antinociceptive effects of D1DR and D2DR antagonists could be reversed by D1DR, D2DR, and D1?D2DR agonists. Gαq, PLC, and IP3 inhibitors also alleviated CCI-induced neuropathic pain. D1DR, D2DR, and D1?D2DR complex agonists all increased the intracellular calcium concentration in primary cultured spinal neurons, and this increase could be reversed by D1DR, D2DR antagonists and Gαq, IP3, PLC inhibitors. D1DR and D2DR antagonists significantly reduced the expression of p-PKC γ, p-CaMKII, p-CREB, and p-MAPKs. Levo -corydalmine ( l -CDL), a monomeric compound in Corydalis yanhusuo W.T. Wang, was found to obviously suppress the formation of the spinal D1?D2DR complex to alleviate neuropathic pain in CCI rats and to decrease the intracellular calcium concentration in spinal neurons. l- CDL-induced inhibition of p-PKC γ, p-MAPKs, p-CREB, and p-CaMKII was also reversed by D1DR, D2DR, and D1?D2DR complex agonists. In conclusion, these results indicate that D1DR and D2DR form a complex and in turn couple with the Gαq protein to increase neuronal excitability via PKC γ, CaMKII, MAPK, and CREB signaling in the spinal cords of CCI rats; thus, they may serve as potential drug targets for neuropathic pain therapy.

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