脊髄におけるNMDARサブユニット発現の上昇を介したGタンパク質共役受容体17による男性マウスの神経障害性疼痛の促進

Neuropathic pain is a prevalent and debilitating chronic condition for which current treatments often provide inadequate relief. This constitutes a significant unmet clinical need, highlighting the importance of identifying novel molecular targets for more effective pharmacotherapy. Synaptic remodeling-mediated central sensitization is a key regulatory factor. Glutamate is a major excitatory transmitter in the central nervous system and binds to NMDA receptors in the postsynaptic membrane to promote synaptic remodeling. In C57 mice with spared nerve injury, it was noted that GPR17 and the GluN2A and GluN2B subunits of the NMDA receptor were elevated in the L4-L6 region of the spinal cord. Lentiviral knockdown of spinal GPR17 attenuated mechanical allodynia, suppressed astrocyte activation, and decreased levels of GluN2A and GluN2B subunits. GPR17 controls neuropathic pain, stimulates astrocyte activation, and NMDA receptor overexpression on neurons. Targeting GPR17 may represent a new therapeutic strategy for the management of neuropathic pain.