Reviews
Pain and bone damage in rheumatoid arthritis: role of leukotriene B4
L.-X. Zheng1, K.-X. Li2, F.-F. Hong3, S.-L. Yang4
- Department of Physiology, College of Medicine, Nanchang University, China.
- Department of Physiology, College of Medicine, Nanchang University, China.
- Department of Experimental Teaching Center, Nanchang University, China.
- Department of Physiology, College of Medicine, Nanchang University, China. slyang@ncu.edu.cn
CER11915
2019 Vol.37, N°5
PI 0872, PF 0878
Reviews
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PMID: 30943138 [PubMed]
Received: 18/11/2018
Accepted : 18/02/2019
In Press: 27/03/2019
Published: 29/08/2019
Abstract
Rheumatoid arthritis is a chronic autoimmune disease characterised by unbearable joint pain as well as bone and cartilage destruction. Although RA development is greatly controlled, the pain and bone damage failed to be relieved and managed. Leukotriene B4 (LTB4) has been proved to play an essential role in the induction of pain and bone damage. The nerve injury of RA can promote the production of LTB4, which act on their receptors, leading to the increased release of pro-inflammatory cytokines and ROS to reduce neuron viability and pain threshold. Moreover, LTB4-BLT1 activation can also increase intracellular calcium concentration and neuron excitability as well as NF-κB pathway activation, which further promote the production of MMP-9 and CXC3R-1. The mutual promotion between LTB4 and neutrophil accumulation accelerates the release of TNF-α and IL-β, which enhance both peripheral and central nerve system sensitisation. LTB4 also involve in TrpV1 channel activation and modulation of P2X3 receptor activation. All above mechanisms contribute to the development of RA pain. IL-23, cPLA2 and PI3K increase the production of CD11b+Gr1high myeloid subtype and calcium concentration, which promote the production of LTB4 and further accelerate IL-17 and TNF activation as well as calcium influx to conduce to osteoclastogenesis, resulting in aggregated bone damage. Our review is the first to conclude the signalling pathways and associated molecules in LTB4-induced pain and bone damage.
