Protease-Mediated Suppression of DRG Neuron Excitability by Commensal Bacteria

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jessica L SessenweinA E Lomax

Abstract

Peripheral pain signaling reflects a balance of pronociceptive and antinociceptive influences; the contribution by the gastrointestinal microbiota to this balance has received little attention. Disorders, such as inflammatory bowel disease and irritable bowel syndrome, are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal gastrointestinal bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse DRG neurons. MET-1 reduced the excitability of DRG neurons by significantly increasing rheobase, decreasing responses to capsaicin (2 μm) and reducing action potential discharge from colonic afferent nerves. The increase in rheobase was accompanied by an increase in the amplitude of voltage-gated K+ currents. A mixture of bacterial protease inhibitors abrogated the effect of MET-1 effects on DRG neuron rheobase. A serine protease inhibitor but not inhibitors of cysteine proteases, acid proteases, metalloproteases, or aminopeptidases abolished the effects of MET-1. The serine protease cathepsin G recapitulated th...Continue Reading

Citations

Nov 1, 2018·Annual Review of Physiology·Luke GrundyStuart M Brierley
Jun 20, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yang YuDavid E Reed
Feb 27, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Qin LiJianhua Li
Mar 7, 2020·The Journal of Physiology·Sabindra PradhanangaAlan E Lomax
Sep 26, 2019·Journal of Neural Transmission·Manon DefayeFrédéric Antonio Carvalho
May 10, 2019·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Mathieu MeleineTim Vanuytsel
Jul 11, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Alan E LomaxDervla O'Malley
Aug 10, 2019·Neural Regeneration Research·Shany G Gofrit, Efrat Shavit-Stein
Mar 11, 2020·Frontiers in Neuroscience·Alexander J DaviesSeog Bae Oh
Sep 26, 2019·British Journal of Anaesthesia·Ran GuoTong Liu
Mar 27, 2021·Cellular and Molecular Life Sciences : CMLS·Amy Marie HollandWerend Boesmans
Jan 5, 2021·Neurobiology of Pain·Valentina N LagomarsinoIsaac M Chiu
Oct 25, 2021·Journal of Thrombosis and Haemostasis : JTH·Robert H LeeSilvio Antoniak
Nov 16, 2021·American Journal of Physiology. Renal Physiology·Nicolas MontalbettiMarcelo D Carattino
Jul 3, 2021·Nature Communications·Murat KirtayZhao-Qi Wang

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