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Papers of the Week

Papers: 25 Apr 2020 - 1 May 2020

Animal Studies

2020 Apr 22


Sensitization of knee-innervating sensory neurons by tumor necrosis factor-α activated fibroblast-like synoviocytes: an in vitro, co-culture model of inflammatory pain.


Chakrabarti S, Hore Z, Pattison LA, Lalnunhlimi S, Bhebhe CN, Callejo G, Bulmer DC, Taams LS, Denk F, Smith E S J
Pain. 2020 Apr 22.
PMID: 32332252.


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-α), 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-α 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-α to promote neuronal sensitization, results that highlight the importance of both non-neuronal and neuronal cells to the development of pain in arthritis.