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: Haruka Omoto, Shinji Matsumura, Manabu Kitano, Shinichiro Miyazaki, Toshiaki Minami, Seiji Ito
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 760 Pg. 42-8 (Aug 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25861935 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• acromelic acid A
• Kainic Acid

Topics

• Animals
• Hyperalgesia (chemically induced, pathology)
• Injections, Spinal
• Kainic Acid (administration & dosage, analogs & derivatives, toxicity)
• Male
• Mice
• Pain Measurement (drug effects, methods)