A Review on Chronic Pain in Rheumatoid Arthritis: A Focus on Activation of NR2B Subunit of N-Methyl-D-Aspartate Receptors.

Ain’ Sabreena Mohd Noh,Che Aishah Nazariah Ismail

doi:10.21315/mjms2020.27.1.2

Ain’ Sabreena Mohd Noh, Che Aishah Nazariah Ismail

Open Access

https://doi.org/10.21315/mjms2020.27.1.2

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Abstract

Chronic pain is a debilitating condition that occurs after tissue damage, which substantially affects the patient’s emotional state and physical activity. The chronic pain in rheumatoid arthritis (RA) is the result of various autoimmune-induced inflammatory reactions in the joints. Both types of peripheral and central pain processing can lead to sensitisation. Non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) can result in potent anti-inflammatory effect. However, these drugs are not able to suppress the pain from RA for a prolonged period. For years, researchers have examined the role of the N-methyl-D-aspartic acid receptor 2B (NR2B) subunit of N-methyl-D-aspartate receptors (NMDAR) in chronic and neuropathic pain models. This NMDAR subtype can be found in at the peripheral and central nervous system and it represents an effective therapy for RA pain management. This review focuses on the NR2B subunit of NMDAR and the different pathways leading to its activation. Furthermore, specific attention is given to the possible involvement of NR2B subunit in the peripheral and central pathogenesis of RA.

Highlights

Rheumatoid Arthritis as a Chronic Pain DiseaseRheumatoid arthritis (RA) is an autoimmune disease caused by the inflammation process in the body
This review focuses on the possible roles and mechanisms of N-methyl-D-aspartate receptors (NMDAR) in the published arthritic and inflammatory-related researches
Despite the availability of certain biologics to suppress and control the inflammatory responses in rheumatoid arthritis (RA), the pain resulted from RA warrants more attention

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease caused by the inflammation process in the body. In the event of chronic inflammation, the sensitisation of inflammatory mediators on the low-threshold mechanosensitive Aβ-fibres may extend widely into laminae I and II of the spinal cord This extension leads to the formation of synaptic networks with nociceptive-specific neurons, among which are the pathways that activates the NR2B subunit [61]. In a rat model of complete Freund’s adjuvant (CFA) induced-inflammation, the injection of NMDAR antagonist MK-801 prominently blocked the aberrant spontaneous discharges and pain-evoked discharges at the arcuate nucleus site This finding is highly suggestive to be related to the increased phosphorylation of the NR2B subunit mediated by PKC and subsequently resulted in the alleviation of thermal and mechanical hyperalgesia [36]. The termination of NR2B subunit activation may be an effective therapy for the arthritic pain in RA patients

Conclusion

Conflict of Interest