title: Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain.
abstract: Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. Animals were separated into 3 groups: the first group received only a skin incision; the second group received nerve crush injury and intraperitoneal vehicle injection; and the third group received nerve crush injury and intraperitoneal etanercept (6 mg/kg). Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index. Plantar thermal and von Frey mechanical withdrawal thresholds recovered faster in the etanercept group than in the control group. On day 7 after crush injury, the numbers of ED-1-positive cells in crushed nerves of the control and etanercept groups were increased compared to that in the sham-treated group. After 21 days, ED-1-positive cells had nearly disappeared from the etanercept group. Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.
authors.affiliation: Department of Hand Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. kiwatsuki@med.nagoya-u.ac.jp
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Iwatsuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Arai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ota
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kato
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Natsume
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kurimoto
authors.forename: Michiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirata
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000187:drug effects; D000068800:Etanercept; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009437:Neuralgia / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000150:complications*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012038:Regeneration / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D014855:Wallerian Degeneration / Q000150:complications
chemical_list: D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept