title: Minocycline inhibits neurogenic inflammation by blocking the effects of tumor necrosis factor-α.
abstract: It has been well established that neurogenic inflammation is one of the major pathological processes underlying inflammatory pain, but there are few effective anti-inflammatory drugs to alleviate such pain. The present study shows that minocycline, a widely used glial activation inhibitor, is effective in reducing neurogenic inflammation. Patch-clamp recordings showed that small sized dorsal root ganglion (DRG) neurons were dramatically excited following intradermal capsaicin injection in the rat hind paw, evidenced by decreased rheobase and membrane threshold. Pretreatment with minocycline (30 mg/kg for 1 day, intraperitoneal injection) blocked the increased neuronal excitability. Western blot and immunostaining of DRG revealed the activation of satellite glial cells (SGCs) following capsaicin injection. The up-regulation of glial fibrillary acidic protein (GFAP) was significantly inhibited by minocycline pre-administration. Measurement of tumor necrosis factor α (TNF-α) and its receptor, TNF-α receptor 1 (TNFR1), showed that minocycline mainly blocked the up-regulation of TNF-α in SGCs and TNFR1s in neurons following capsaicin injection. The pivotal role of TNF-α in neurogenic inflammation was further supported by the findings that incubation DRG with TNF-α mimicked the increased excitability of DRG neurons induced by capsaicin injection, and that TNF-α application enhanced cutaneous vasodilation in the hind paws induced by antidromic electrical stimulation of dorsal roots. Based on these results, we propose that minocycline is a potential therapeutic drug that can reduce neuronal excitability and neurogenic inflammation by working on SGCs to inhibit the expression of TNF-α.
authors.affiliation: Department of Psychology, College of Science, University of Texas at Arlington, Arlington, TX, USA.|Department of Neurobiology, Tai Shan Medical University, Tai'an, Shan Dong Province, China.
authors.forename: Kerui
authors.initials: K
authors.lastname: Gong
authors.affiliation: Department of Psychology, College of Science, University of Texas at Arlington, Arlington, TX, USA.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Psychology, College of Science, University of Texas at Arlington, Arlington, TX, USA.
authors.forename: Perry N
authors.initials: PN
authors.lastname: Fuchs
authors.affiliation: Department of Psychology, College of Science, University of Texas at Arlington, Arlington, TX, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
keywords: capsaicin; dorsal root ganglion; minocycline; neurogenic inflammation; satellite glial cells; tumor necrosis factor-α