Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy.

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Dina OA, Khasar SG, Alessandri-Haber N, Bogen O, Chen X, Green PG, Reichling DB, Messing RO, Levine JD

Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy.

Eur J Neurosci. 2008 Sep;28(6):1180-90. doi: 10.1111/j.1460-9568.2008.06425.x. Epub 2008 Sep 9.

PubMed ID

18783367 [ View in PubMed

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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 beta-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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Capsaicin	Amine oxidase [flavin-containing] A	Protein	Humans	Unknown	Inhibitor	Details
Capsaicin	Dopamine beta-hydroxylase	Protein	Humans	Unknown	Inhibitor	Details