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Review
. 2022 Jul 18:15:2005-2013.
doi: 10.2147/JPR.S367982. eCollection 2022.

Role of N-Methyl-D-Aspartate Receptor NR2B Subunit in Inflammatory Arthritis-Induced Chronic Pain and Peripheral Sensitized Neuropathic Pain: A Systematic Review

Yu Meng  1 , Hai Li Shen  2
Affiliations
Review

Role of N-Methyl-D-Aspartate Receptor NR2B Subunit in Inflammatory Arthritis-Induced Chronic Pain and Peripheral Sensitized Neuropathic Pain: A Systematic Review

Yu Meng et al. J Pain Res. .

Abstract

Arthritis is a common clinical disease that affects millions of people in the world. The most common types of arthritis are osteoarthritis and rheumatoid arthritis. Inflammatory arthritis (IA), a chronic painful disease, is characterized by synovitis and cartilage destruction in the early stages. Pathologically, IA causes inflammatory changes in the joints and eventually leads to joint destruction. Pain is associated with inflammation and abnormal regulation of the nervous system pathways involved in pain promotion and inhibition. In addition, the occurrence of pain is associated with depression and anxiety. We found that there are many factors affecting pain, in addition to inflammatory factors, glutamate receptor may be the possible cause of long-term chronic pain caused by IA. N-methyl-d-aspartate receptor subunit 2B (NR2B) has been reported to involved in IA and nervous system diseases, especially peripheral neuropathic pain. In this review, we summarized the mechanisms of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor in peripheral nerve sensitization during IA and chronic pain.

Keywords: NR2B subunit; inflammatory arthritis; inflammatory factors; neuropathic pain; peripheral sensitization.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
NMDA is composed of a highly homologous extracellular amino-terminal (ATD), a bilobal ligand-binding domain (LBD), three transmembrane regions, a membrane helix (MD) composed of a reentrant ion pore-lining ring, and a more dispersed intracellular carboxy-terminal domain (CTD). Picture excerpt from Vyklicky et al (PDB code 4TLM).
Figure 2
Figure 2
Induction of immune destruction and degeneration leads to occurrence of inflammatory arthritis and pain. The NR2B subunit is activated and its content as well as phosphorylation levels increase, which is associated with the expressions of inflammatory factors. Dorsal root ganglion (DRG) cells exhibit a sensitization reaction under the influence of the NR2B signal pathway and phosphorylation. Taking the NR2B subunit as the target, reactivity in DRG causes changes in inflammatory factors and gated ion channels in neurons and Ca2+ influx, resulting in peripheral sensitization and long-term chronic pain. Picture excerpt from Buch et al.
See this image and copyright information in PMC

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Grants and funding

This study is funded by Gansu Province Natural Science Foundation Project (ID: 20JR10RA736).