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Updated: Jun 20, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
N-methyl-d-aspartate receptor subunits interacting with regulators mediate neuropathic pain: from mechanisms to
Junzi Peng1, Pengcheng Yi2, Yan Tian3
1Department of Anesthesiology, the Second Affiliated Hospital, Jiangxi medical College, Nanchang University, 330006 Nanchang, Jiangxi, China; The First Clinical Medical College of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
Abstract:
NMDARs and their interacting proteins drive central sensitization in neuropathic pain, yet their pathological effects are critically shaped by upstream neuroendocrine regulators. This review synthesizes evidence across three dimensions: (i) glucocorticoids amplify pain via spinal glucocorticoid receptor signaling, and prior stress history reprograms HPA axis reactivity, thereby determining individual pain susceptibility; (ii) sex hormones produce divergent effects: estrogen exacerbates while progesterone protects and pain mechanisms are sexually dimorphic, with males and females engaging distinct immune and neuronal pathways; (iii) current therapies (ketamine, gabapentinoids) have significant limitations. Emerging preclinical strategies include neuroendocrine-directed interventions (glucocorticoid receptor antagonists, progesterone, sex-stratified trial designs) alongside protein-protein interaction disruptors targeting α2δ-1, Panx1, or PSD-95. Collectively, targeting upstream hormonal drivers offers a paradigm shift from broad NMDAR blockade toward more selective and tolerable treatments, though rigorous validation across sexes and pain phases remains essential.
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