title: Post-injury administration of minocycline: an effective treatment for nerve-injury induced neuropathic pain.
abstract: Neuropathic pain is an intractable clinical problem, affecting millions of people worldwide. Preemptive administration of minocycline has been confirmed useful for treating neuropathic pain by inhibiting spinal microglia activation and consequently lowering proinflammatory cytokine expression. However, most patients with neuropathic pain have no chance to receive preemptive treatment and it remains unclear whether there is a therapeutic time window for post treatment with minocycline. The present study is to confirm the effect and the therapeutic time window of intrathecal minocycline on spinal nerve ligation (SNL)-induced neuropathic pain after lesion. Behavioral test and immunohistochemistry are utilized to determine the variation of mechanical allodynia and microglia phosphorylated-p38 (p-p38) expression respectively after intrathecal minocycline. Results showed that post-injury intrathecal minocycline attenuated mechanical allodynia effectively together with inhibiting spinal microglia p-p38 expression on post operative day (POD) 1, POD 3 and POD 7. Additionally, results from POD 10 and POD 21 showed that intrathecal minocycline suppressed spinal microglia p-p38 expression but without any effects on reversing mechanical allodynia. It is concluded that post-injury intrathecal minocycline is an effective therapeutic intervention for treating SNL-induced neuropathic pain by inhibiting spinal microglia activation. Accordingly, there is indeed a therapeutic time window for post-injury intrathecal minocycline, which is the initiation stage of neuropathic pain development.
authors.affiliation: Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, West Changle Road 169#, Xi'an, Shaan Xi 710032, China. meixiaopengmxp@126.com
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Mei
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Xu
mesh_terms: D000818:Animals; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000503:physiopathology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008911:Minocycline