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Neuropathic pain, a major health problem affecting 7-10% of the global population, lacks effective treatment due to its elusive mechanisms. Cholecystokinin-positive (CCK+) neurons in the spinal dorsal horn (SDH) are critical for neuropathic pain, yet the underlying molecular mechanisms remain unclear. Here, we show that the membrane estrogen receptor G-protein coupled estrogen receptor (GPER/GPR30) in spinal neurons was significantly upregulated in chronic constriction injury (CCI) mice and that inhibition of GPR30 in CCK+ neurons reversed CCI-induced neuropathic pain. Furthermore, GPR30 in spinal CCK+ neurons was essential for the enhancement of AMPA-mediated excitatory synaptic transmission in CCI mice. Moreover, GPR30 was expressed in spinal CCK+ neurons that received direct projection from the primary sensory cortex (S1-SDH). Chemogenetic inhibition of S1-SDH post-synaptic neurons alleviated CCI-induced neuropathic pain. Conversely, chemogenetic activation of these neurons mimicked neuropathic pain symptoms, which were attenuated by spinal inhibition of GPR30. Finally, we confirmed that GPR30 in S1-SDH post-synaptic neurons was required for CCI-induced neuropathic pain. Taken together, our findings suggest that GPR30 in spinal CCK+ neurons and S1-SDH post-synaptic neurons is pivotal for neuropathic pain, thereby representing a promising therapeutic target for neuropathic pain.
Pubmed ID: 41432054
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsThe National Natural Science Foundation of China (NSFC) is an organization directly affiliated to the State Council for the management of the National Natural Science Fund. # In accordance with the guiding principles, policies and plans for the development of science and technology in China and by adopting the operating mechanisms for the National Natural Science Fund which conform to the socialism market economic system, NSFC supports basic research and some of applied research, identifies and fosters talented researchers in the realm of science and technology, accelerates the progress of science and technology, and promotes the socioeconomic development in China by giving full play the guidance and coordinating role of the National Natural Science Fund from the central government. # NSFC is in charge of the management of the National Natural Science Fund. It compiles and promulgates the annual Guide to Programs for basic research and some of applied research, handles applications of research projects, and organizes peer review and select the best projects to support. It endeavors to create an academic environment conducive to innovation. # NSFC cooperates with the Ministry of Science and Technology to formulate the principles, policies and plans for the development of basic research in China. When entrusted, it provides consultation and undertakes related assignments on major issues for the development of high technology and applied research in China. # NSFC gives help and support to other Chinese foundations in natural sciences. # NSFC establishes contacts with governmental departments in charge of science and technology, science foundations and related academic organizations in other countries and carries out international cooperation and exchange. # NSFC is responsible for the administration, supervision and guidance of the subordinated bodies. # NSFC undertakes other tasks entrusted by the State Council and the State Leading Group for Science and Technology and Education.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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