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Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy

Authors

  • Olayinka A. Dina,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • Sachia G. Khasar,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • Nicole Alessandri-Haber,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • Oliver Bogen,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • Xiaojie Chen,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • Paul G. Green,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • David B. Reichling,

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
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  • Robert O. Messing,

    1. Department of Neurology, University of California at San Francisco, CA, USA
    2. Division of Neuroscience and Biomedical Sciences, University of California at San Francisco, CA, USA
    3. Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA
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  • Jon D. Levine

    1. Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA
    2. UCSF NIH Pain Center, University of California at San Francisco, CA, USA
    3. Division of Neuroscience and Biomedical Sciences, University of California at San Francisco, CA, USA
    4. Department of Medicine, University of California at San Francisco, CA 94143 0440, USA
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Errata

This article is corrected by:

  1. Errata: Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy Volume 30, Issue 11, 2235, Article first published online: 25 November 2009

Dr J. D. Levine, 6Department of Medicine, as 6above.
E-mail: Jon.Levine@ucsf.edu

Abstract

The neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. As some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO), we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin-stimulated epinephrine release, an effect enhanced in ethanol-fed rats. mRNA for enzymes in dorsal root ganglia involved in catecholamine uptake and metabolism, dopamine β-hydroxylase and MAO-A, were decreased by neonatal administration of capsaicin. Ethanol-induced hyperalgesia was attenuated by systemic and local peripheral administration of inhibitors of MAO-A, reduction of norepinephrine transporter (NET) in sensory neurons and a NET inhibitor. Finally, intradermal injection of 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), a neurotoxic MAO-A catecholamine metabolite, produced robust mechanical hyperalgesia. These observations suggest that catecholamines in nociceptors are metabolized to neurotoxic products by MAO-A, which can cause neuronal dysfunction underlying neuropathic pain.

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