Pain-releasing action of Platelet-activating factor (PAF) antagonists in neuropathic pain animal models and the mechanisms of action

N. Motoyama, K. Morita, T. Kitayama, S. Shiraishi, Y. Uezono, Fusanori Nishimura, Takashi Kanematsu, Toshihiro Dohi

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抄録

Background: Platelet-activating factor (PAF) has been implicated in the pathology of neuropathic pain. Previous studies reported that PAF receptor (PAF-R) antagonists have varied anti-allodynia effects by route of administration and nerve injury models in rats. Methods: The present study elucidated the effectiveness of PAF antagonists against neuropathic pain in four different models of peripheral nerve injury and provided insights into the mode of anti-allodynia action. Results: PAF antagonists, TCV-309, BN 50739 and WEB 2086 by intravenous (i.v.) and oral administration have potent and long-lasting anti-allodynia action in mice neuropathic pain models. Treatment with PAF antagonists before surgery delayed the initiation of allodynia until the effects of these treatments were abolished. Intrathecal (i.t.) injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. I.t. injection of the glycine receptor (GlyR)α3 siRNA reduced the anti-allodynia effect of PAF antagonists. This evidence suggests that the anti-allodynia effect of PAF antagonists is at least in part mediated by spinal relief of PAF-induced dysfunction of GlyRα3. An analysis of the mode of anti-allodynia action of TCV-309 in vivo revealed a competitive action against PAF shortly after the injection of TCV-309, converting to a non-competitive action later. Conclusions: The present results revealed the effectiveness in anti-allodynia of PAF antagonists in different nerve injury models, and the unique mode of action; long-lasting anti-allodynia effects mediated by spinal GlyRa3 with a competitive manner at the initial stage and the following non-competitive manner of inhibition.

元の言語英語
ページ(範囲)1156-1167
ページ数12
ジャーナルEuropean Journal of Pain (United Kingdom)
17
発行部数8
DOI
出版物ステータス出版済み - 9 2013
外部発表Yes

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Platelet Activating Factor
Hyperalgesia
Neuralgia
Animal Models
Pain
WEB 2086
Small Interfering RNA
Glycine Receptors
Spinal Injections
Peripheral Nerve Injuries
Injections
Wounds and Injuries
Intravenous Administration
Oral Administration
Pathology

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

これを引用

Pain-releasing action of Platelet-activating factor (PAF) antagonists in neuropathic pain animal models and the mechanisms of action. / Motoyama, N.; Morita, K.; Kitayama, T.; Shiraishi, S.; Uezono, Y.; Nishimura, Fusanori; Kanematsu, Takashi; Dohi, Toshihiro.

:: European Journal of Pain (United Kingdom), 巻 17, 番号 8, 09.2013, p. 1156-1167.

研究成果: ジャーナルへの寄稿記事

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abstract = "Background: Platelet-activating factor (PAF) has been implicated in the pathology of neuropathic pain. Previous studies reported that PAF receptor (PAF-R) antagonists have varied anti-allodynia effects by route of administration and nerve injury models in rats. Methods: The present study elucidated the effectiveness of PAF antagonists against neuropathic pain in four different models of peripheral nerve injury and provided insights into the mode of anti-allodynia action. Results: PAF antagonists, TCV-309, BN 50739 and WEB 2086 by intravenous (i.v.) and oral administration have potent and long-lasting anti-allodynia action in mice neuropathic pain models. Treatment with PAF antagonists before surgery delayed the initiation of allodynia until the effects of these treatments were abolished. Intrathecal (i.t.) injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. I.t. injection of the glycine receptor (GlyR)α3 siRNA reduced the anti-allodynia effect of PAF antagonists. This evidence suggests that the anti-allodynia effect of PAF antagonists is at least in part mediated by spinal relief of PAF-induced dysfunction of GlyRα3. An analysis of the mode of anti-allodynia action of TCV-309 in vivo revealed a competitive action against PAF shortly after the injection of TCV-309, converting to a non-competitive action later. Conclusions: The present results revealed the effectiveness in anti-allodynia of PAF antagonists in different nerve injury models, and the unique mode of action; long-lasting anti-allodynia effects mediated by spinal GlyRa3 with a competitive manner at the initial stage and the following non-competitive manner of inhibition.",
author = "N. Motoyama and K. Morita and T. Kitayama and S. Shiraishi and Y. Uezono and Fusanori Nishimura and Takashi Kanematsu and Toshihiro Dohi",
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T1 - Pain-releasing action of Platelet-activating factor (PAF) antagonists in neuropathic pain animal models and the mechanisms of action

AU - Motoyama, N.

AU - Morita, K.

AU - Kitayama, T.

AU - Shiraishi, S.

AU - Uezono, Y.

AU - Nishimura, Fusanori

AU - Kanematsu, Takashi

AU - Dohi, Toshihiro

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N2 - Background: Platelet-activating factor (PAF) has been implicated in the pathology of neuropathic pain. Previous studies reported that PAF receptor (PAF-R) antagonists have varied anti-allodynia effects by route of administration and nerve injury models in rats. Methods: The present study elucidated the effectiveness of PAF antagonists against neuropathic pain in four different models of peripheral nerve injury and provided insights into the mode of anti-allodynia action. Results: PAF antagonists, TCV-309, BN 50739 and WEB 2086 by intravenous (i.v.) and oral administration have potent and long-lasting anti-allodynia action in mice neuropathic pain models. Treatment with PAF antagonists before surgery delayed the initiation of allodynia until the effects of these treatments were abolished. Intrathecal (i.t.) injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. I.t. injection of the glycine receptor (GlyR)α3 siRNA reduced the anti-allodynia effect of PAF antagonists. This evidence suggests that the anti-allodynia effect of PAF antagonists is at least in part mediated by spinal relief of PAF-induced dysfunction of GlyRα3. An analysis of the mode of anti-allodynia action of TCV-309 in vivo revealed a competitive action against PAF shortly after the injection of TCV-309, converting to a non-competitive action later. Conclusions: The present results revealed the effectiveness in anti-allodynia of PAF antagonists in different nerve injury models, and the unique mode of action; long-lasting anti-allodynia effects mediated by spinal GlyRa3 with a competitive manner at the initial stage and the following non-competitive manner of inhibition.

AB - Background: Platelet-activating factor (PAF) has been implicated in the pathology of neuropathic pain. Previous studies reported that PAF receptor (PAF-R) antagonists have varied anti-allodynia effects by route of administration and nerve injury models in rats. Methods: The present study elucidated the effectiveness of PAF antagonists against neuropathic pain in four different models of peripheral nerve injury and provided insights into the mode of anti-allodynia action. Results: PAF antagonists, TCV-309, BN 50739 and WEB 2086 by intravenous (i.v.) and oral administration have potent and long-lasting anti-allodynia action in mice neuropathic pain models. Treatment with PAF antagonists before surgery delayed the initiation of allodynia until the effects of these treatments were abolished. Intrathecal (i.t.) injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. I.t. injection of the glycine receptor (GlyR)α3 siRNA reduced the anti-allodynia effect of PAF antagonists. This evidence suggests that the anti-allodynia effect of PAF antagonists is at least in part mediated by spinal relief of PAF-induced dysfunction of GlyRα3. An analysis of the mode of anti-allodynia action of TCV-309 in vivo revealed a competitive action against PAF shortly after the injection of TCV-309, converting to a non-competitive action later. Conclusions: The present results revealed the effectiveness in anti-allodynia of PAF antagonists in different nerve injury models, and the unique mode of action; long-lasting anti-allodynia effects mediated by spinal GlyRa3 with a competitive manner at the initial stage and the following non-competitive manner of inhibition.

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