Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy.
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.
Dina
Olayinka A
OA
Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA, USA.
Khasar
Sachia G
SG
Alessandri-Haber
Nicole
N
Bogen
Oliver
O
Chen
Xiaojie
X
Green
Paul G
PG
Reichling
David B
DB
Messing
Robert O
RO
Levine
Jon D
JD
D020269:Alcoholic Neuropathy / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology
D002395:Catecholamines; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016376:Oligonucleotides, Antisense; D018689:Sensory System Agents; D000431:Ethanol; D010293:Pargyline; D008995:Monoamine Oxidase; D003010:Clorgyline; D002211:Capsaicin; D003891:Desipramine
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