AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain. (Articolo in rivista)

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  • AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain. (Articolo in rivista) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Alternative label
  • Costa B. 1, Siniscalco D. 2, Trovato A.E. 3, Comelli F. 1, Sotgiu M.L. 4, Colleoni M. 3, Maione S. 2, Rossi F. 2, Giagnoni G. 1 (2006)
    AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain.
    in British journal of pharmacology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Costa B. 1, Siniscalco D. 2, Trovato A.E. 3, Comelli F. 1, Sotgiu M.L. 4, Colleoni M. 3, Maione S. 2, Rossi F. 2, Giagnoni G. 1 (literal)
Pagina inizio
  • 1022 (literal)
Pagina fine
  • 1032 (literal)
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  • Research devoted to the advancement of pain therapy (literal)
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  • 148 (literal)
Rivista
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  • Citazioni al 26/01/09: 24 Citazioni al 2007 (escluso autocitazioni): 19 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1. Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milano, Italy 2. Department of Experimental Medicine, Section of Pharmacology \"£L. Donatelli\", Second University of Naples, Napoli, Italy 3. Department of Pharmacology, University of Milano, Milano, Italy 4. Institute of Bioimages and Molecular Physiology, CNR, Segrate (MI), Italy (literal)
Titolo
  • AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain. (literal)
Abstract
  • 1. An attractive alternative to the use of direct agonists at the cannabinoid receptor type 1 (CB1) in the control of neuropathic pain may be to potentiate the actions of endogenous cannabinoids. Thus, the effects of AM404, an inhibitor of anandamide uptake, were assessed in an experimental model of neuropathic pain in rats. 2. Daily treatment with AM404 prevented, time- and dose-dependently, the development of thermal hyperalgesia and mechanical allodynia in neuropathic rats. Antagonists at cannabinoid CB1 or CB2 receptors, or at the transient receptor potential vanilloid type 1 receptor, each partially reversed effects induced by AM404. A complete reversal was obtained when the three antagonists were given together, suggesting that all three receptors are involved. 3. AM404 treatment affected two pathways involved in the generation and maintenance of neuropathic pain, one mediated by nitric oxide (NO) and the other by cytokines. AM404 completely prevented the overproduction of NO and the overexpression of nNOS, inhibited the increase in tumour necrosis factor a (TNFa) and enhanced the production of interleukin-10. Both NO and TNFa are known to contribute to the apoptotic process, which plays an important role in the establishment of chronic pain states. AM404 treatment prevented the increase in the ratio between pro- and antiapoptotic gene bax/bcl-2 expression observed in the spinal cord of neuropathic rats. 4. Taken together, these findings suggest that inhibition of endocannabinoid uptake, by blocking the putative anandamide carrier, results in the relief of neuropathic pain and may represent a novel strategy for treating chronic pain. (literal)
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