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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2026; 17(1): 110108
Published online Jan 15, 2026. doi: 10.4239/wjd.v17.i1.110108
Published online Jan 15, 2026. doi: 10.4239/wjd.v17.i1.110108
Targeting N-methyl-D-aspartate 2B receptor in painful diabetic neuropathy – mechanisms, challenges, and emerging therapeutics
Nayab Khalid, Department of Physiology, Islam Medical College, Sialkot City 51040, Punjab, Pakistan
Nazlahshaniza Shafin, Che Aishah Nazariah Ismail, Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian 16150, Kelantan, Malaysial
Idris Long, Department of Biomedicine, School of Health Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian, Kota Bharu 16150, Kelantan, Malaysia
Hidani Hasim, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Bertam 13200, Pulau Pinang, Malaysia
Author contributions: Khalid N and Ismail CAN contributed written ideas and insights, conceptualized and prepared the manuscript; Shafin N, Hasim H, and Long I proofread the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Che Aishah Nazariah Ismail, PhD, Lecturer, Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian 16150, Kelantan, Malaysia. aishahnazariah@usm.my
Received: May 29, 2025
Revised: July 31, 2025
Accepted: December 2, 2025
Published online: January 15, 2026
Processing time: 230 Days and 9.3 Hours
Revised: July 31, 2025
Accepted: December 2, 2025
Published online: January 15, 2026
Processing time: 230 Days and 9.3 Hours
Core Tip
Core Tip: The N-methyl-D-aspartate receptor 2B (NMDAR-2B) plays a pivotal role in the pathophysiology of painful diabetic neuropathy (DN). In this review, the contribution of NMDAR-2B to oxidative stress, neuroinflammation, and central sensitisation was underscored. Experimental and clinical data linking NMDAR-2B upregulation with chronic pain were also discussed. Furthermore, emerging therapeutics targeting the receptor were evaluated, while outlining the translational challenges. Comprehending the molecular interplay of NMDAR-2B with glial cells and signalling pathways might also provide valuable insight for developing multi-targeted or precision-based therapies to improve painful DN management.