Alcohol-induced stress in painful alcoholic neuropathy.
Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy, the severity of which increases during alcohol withdrawal. Chronic alcohol consumption also produces a sustained increase in stress hormones, epinephrine and corticosterone, that is exacerbated during alcohol withdrawal. We report that adrenal medullectomy and administration of a glucocorticoid receptor antagonist, mifepristone (RU 38486), both prevented and reversed a model of painful peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of stress levels of epinephrine to rats that had undergone adrenal medullectomy and were being fed the alcohol diet reconstituted this phenotype. Intrathecal administration of oligodeoxynucleotides antisense to the beta(2)-adrenergic- or glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects of ethanol. Our results suggest a convergence of the effects of mediators of the hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the induction and maintenance of alcohol-induced painful peripheral neuropathy.
Dina
Olayinka A
OA
Department of Oral & Maxillofacial Surgery, University of California at San Francisco, CA 94143-0440, USA.
Khasar
Sachia G
SG
Alessandri-Haber
Nicole
N
Green
Paul G
PG
Messing
Robert O
RO
Levine
Jon D
JD
D000315:Adrenalectomy / Q000379:methods; D020269:Alcoholic Neuropathy / Q000150:complications*; D000438:Alcohols / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood; D006727:Hormone Antagonists / Q000008:administration & dosage; D006930:Hyperalgesia / Q000517:prevention & control; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage; D009437:Neuralgia / Q000209:etiology* / Q000517:prevention & control; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013312:Stress, Physiological / Q000139:chemically induced*; D013997:Time Factors; D016047:Zalcitabine / Q000008:administration & dosage
D000438:Alcohols; D006727:Hormone Antagonists; D016376:Oligonucleotides, Antisense; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D016047:Zalcitabine; D017239:Paclitaxel; D004837:Epinephrine