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Inducing Plasticity of Astrocytic Receptors by Manipulation of Neuronal Firing Rates
Published on: March 20, 2014
Mirror image pain mediated by D2 receptor regulation of astrocytic Cx43 phosphorylation and channel opening
Qinghu Yang1, Ming Jiang1, Sen Xu2
1School of Life Science & Research Center for Natural Peptide Drugs, Shaanxi Engineering & Technological Research Centre for Conservation & Utilization of Regional Biological Resources, Yanan University, Yanan 716000, China; Yanan Engineering & Technological Research Centre for Resource Peptide Drugs, Yanan 716000, China; Yanan Key Laboratory for Neural Immuno-Tumor and Stem Cell, Yanan 716000, China.
Abstract:
Mirror image pain (MIP), a clinical syndrome of contralateral pain hypersensitivity caused by unilateral injury, has been identified in various neuropathological conditions. Gap junctional protein Connexin 43 (Cx43), its phosphorylation levels and dopamine D2 receptor (DRD2) play key integrating roles in pain processing. We presume D2DR activity may affect Cx43 hemichannel opening via Cx43 phosphorylation levels to regulate MIP. This study shows that spinal astrocytic Cx43 directly interacts with DRD2 to mediate MIP. DRD2 and Cx43 expression levels were asymmetrically elevated in bilateral spinal during MIP, and DRD2 modulated the opening of primary astrocytic Cx43 hemichannels. Furthermore, Cx43 phosphorylation at Ser373 was increased during MIP, but decreased in DRD2 knockout (KO) mice. Finally, activation of spinal protein kinase A (PKA) altered the expression of Cx43 and its phosphorylation bilaterally, thus reversing the analgesic effect in DRD2 KO mice. Together, these data reveal that spinal Cx43 phosphorylation and channel opening are regulated by DRD2 via PKA activation, and that spinal Cx43 and DRD2 are key molecular sensors mediating mirror image pain.
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