title: Combination of tramadol with minocycline exerted synergistic effects on a rat model of nerve injury-induced neuropathic pain.
abstract: Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.
authors.affiliation: Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Mei
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Xu
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010147:Pain Measurement; D059348:Peripheral Nerve Injuries / Q000150:complications*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D016760:Proto-Oncogene Proteins c-fos; D014147:Tramadol; D008911:Minocycline