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Papers of the Week

Papers: 2 Jul 2022 - 8 Jul 2022

Pharmacology/Drug Development

2022 Jul 01

J Physiol

Sensitisation of colonic nociceptors by TNFα is dependent on TNFR1 expression and p38 MAPK activity.


Barker KH, Higham JP, Pattison LA, Taylor TS, Chessell IP, Welsh F, Smith E SJ, Bulmer DC
J Physiol. 2022 Jul 01.
PMID: 35775903.


The pro-inflammatory cytokine TNFα is elevated in GI disease and sensitises colonic afferents via modulation of TRPA1 and Na 1.8 activity. We further develop this understanding by demonstrating a role for p38 MAPK and TRPV1 in TNFα mediated colonic afferent sensitisation. Specifically, we show that: TNFα sensitises sensory neurons and colonic afferents to the TRPV1 agonist capsaicin. TNFα-mediated sensitisation of sensory neurons and colonic nociceptors is dependent on TNFR1 expression. TNFα sensitisation of sensory neurons and colonic afferents to capsaicin and noxious ramp distension is abolished by inhibition of p38 MAPK. Collectively this data supports the utility of targeting TNFα, TNFR1 and their downstream signalling via p38 MAPK for the treatment of visceral pain in GI disease.