Neuropathic pain (NP) is a chronic pain condition caused by nerve damage. Current NP treatments have limited efficacy and significant side effects. Emerging evidence demonstrates that N-methyl-d-aspartate receptors (NMDARs) play a key role in the development of NP, especially in their pre- and postsynaptic functions. This review provides an overview of the mechanistic roles of NMDARs in NP, focusing on their subunit structures and involvement in pain transmission. The interactions between NMDARs and other neurotransmitter receptors are further discussed, emphasizing NMDARs as a promising therapeutic target. Finally, we discuss the pharmacologic mechanisms of NMDARs relevant to pain management and nonpharmacologic interventions, which have not been covered in previous reviews. This review aims to advance future research on NMDAR-mediated mechanisms in NP and promote the development of targeted, low–side effect therapeutic strategies.
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