Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT2R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies.

摘要: Background The clinical efficacy of the Angiotensin II (AngII) receptor AT2R antagonist EMA401, a novel peripherally-restricted analgesic, was reported recently in post-herpetic neuralgia. While previous studies have shown that is expressed by nociceptors human DRG (hDRG), and EMA401 inhibits capsaicin responses cultured hDRG neurons, expression levels its endogenous ligands AngII AngIII neuropathic pain tissues, their signalling pathways, require investigation. We immunostained AngII, TRPV1 control post-mortem avulsion injured hDRG, nerves, neurons. AngIII, Ang-(1-7) were quantified ELISA. The vitro effects agonist C21, Nerve growth factor (NGF) measured on neurite lengths; NGF p38 p42/44 MAPK using quantitative immunofluorescence, calcium imaging.