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Department of Pharmacology

 
Author(s): 
Chakrabarti, S, Hore, Z, Pattison, L, Lalnunhlimi, S, Bhebhe, C, Callejo, G, Bulmer, D, Taams, L, Denk, F, Smith, E
Abstract: 

Pain is a principal contributor to the global burden of arthritis with peripheral sensitization being a major cause of arthritis-related pain. Within the knee joint, distal endings of dorsal root ganglion neurons (knee neurons) interact with fibroblast-like synoviocytes (FLS) and the inflammatory mediators they secrete, which are thought to promote peripheral sensitization. Correspondingly, RNA-sequencing has demonstrated detectable levels of pro-inflammatory genes in FLS derived from arthritic patients. This study confirms that stimulation with tumor necrosis factor (TNF-, results in expression of pro-inflammatory genes in mouse and human FLS (derived from OA and RA patients), as well as increased secretion of cytokines from mouse TNF- stimulated FLS (TNF-FLS). Electrophysiological recordings from retrograde labelled knee neurons co-cultured with TNF-FLS, or supernatant derived from TNF-FLS, revealed a depolarized resting membrane potential, increased spontaneous action potential firing and enhanced TRPV1 function, all consistent with a role for FLS in mediating the sensitization of pain-sensing nerves in arthritis. Therefore, data from this study demonstrate the ability of FLS activated by TNF- to promote neuronal sensitization, results that highlight the importance of both non-neuronal and neuronal cells to the development of pain in arthritis.

Publication ID: 
1190496
Published date: 
1 September 2020
Publication source: 
manual
Publication type: 
Journal articles
Journal name: 
Pain
Publication volume: 
Publisher: 
Wolters Kluwer Health
Parent title: 
Edition: 
Publication number: