title: Comparison of mechanisms of allodynia induced by acromelic acid A between early and late phases.
abstract: We previously showed that intrathecal administration of acromelic acid A (ACRO-A) provoked tactile allodynia in mice. As well, recent studies have demonstrated that the activation of NMDA glutamate receptor-neuronal nitric oxide synthase (nNOS) pathway and glia play crucial roles in the development and maintenance of neuropathic pain. In order to clarify their involvement in ACRO-A-induced allodynia, we investigated the effects of various agents on two mouse models at early and late-phase allodynia. The agents employed were Ca(2+) channel α2δ ligands, NMDA and AMPA receptor antagonists, nNOS, and Ca(2+)/calmodulin kinase II inhibitors. When injected simultaneously with ACRO-A, all of these agents blocked allodynia in the early-phase group; however, they did not block allodynia when injected 7 days after the administration of ACRO-A in the late-phase group. In order to block glial activation, astrocytic inhibitor L-α-aminoadipate (LAA) or microglial inhibitor minocycline was administrated, and allodynia was examined on day 7. Activations of nNOS and glia in the spinal cord were histochemically examined at 1 h or 1 week after injection of ACRO-A. We found that nNOS activity increased 1 h after ACRO-A injection; however, it did not increase 1 week after ACRO-A injection. Conversely, microglial activation was observed 1 week after ACRO-A injection and was significantly inhibited with minocycline treatment. Moreover, only LAA was found to inhibit late-phase allodynia. In this study, we demonstrate that NMDA receptor activation is involved only in ACRO-A-induced tactile allodynia in the early phase, and that spinal astrocytic activation contributes to allodynia in the late phase.
authors: Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan. Electronic address: Haruka.omoto@gmail.com.
authors: Haruka
authors: H
authors: Omoto
authors: Department of Medical Chemistry, Kansai Medical University, Hirakata 573-1010, Japan. Electronic address: matsumur@hirakata.kmu.ac.jp.
authors: Shinji
authors: S
authors: Matsumura
authors: Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan. Electronic address: nisiitai509@yahoo.co.jp.
authors: Manabu
authors: M
authors: Kitano
authors: Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan. Electronic address: ane053@poh.osaka-med.ac.jp.
authors: Shinichiro
authors: S
authors: Miyazaki
authors: Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan. Electronic address: ane022@poh.osaka-med.ac.jp.
authors: Toshiaki
authors: T
authors: Minami
authors: Department of Medical Chemistry, Kansai Medical University, Hirakata 573-1010, Japan. Electronic address: ito@hirakata.kmu.ac.jp.
authors: Seiji
authors: S
authors: Ito
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced* / Q000473:pathology*; D007278:Injections, Spinal; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*
chemical_list: C051743:acromelic acid A; D007608:Kainic Acid
keywords: Acromelic acid; Allodynia; Neuropathic pain; Spinal cord