Chemokine Signaling and the Management of Neuropathic Pain

  1. Fletcher A. White1,
  2. Polina Feldman2 and
  3. Richard J. Miller3
  1. 1 Cell Biology, Neurobiology & Anatomy, and Anesthesiology
  2. 2 Neuroscience Graduate Program, Loyola University, Stritch School of Medicine, Chicago, IL 60611
  3. 3 Molecular Pharmacology & Biological Chemistry, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611

Abstract

In the 1930s, presumably after the repeal of prohibition, laborers who came to work at a certain rubber factory found that a drink at the end of the working day did little to relax them. Flushing and nausea, vertigo, headache, and hypotension were the more obvious effects of the workers’ intake of alcohol. It turned out that exposure to disulfiram, a chemical used at the rubber factory, made the imbibing of alcohol aversive. By 1951, disulfiram was dispensed as a drug, named Antabuse, for the treatment of alcoholism. Disulfiram functions as an inhibitor of aldehyde dehydrogenase, and the accumulation of acetaldehyde in patients who receive disulfiram and then drink alcohol is the basis of the disulfiram–ethanol reaction. So why should disulfiram, clearly implicated in inhibiting ethanol metabolism, be effective in treating cocaine addiction? At first consideration, a number of psychological and social explanations come to mind: cocaine use is comorbid with alcohol abuse; the psychological deterrent created in treated alcoholics is transferred to the effects of cocaine intake. A series of clinical trials has established that disulfiram is specific for cocaine use per se; indeed, disulfiram inhibits dopamine β-hydrolase and thereby plays directly to the mechanisms of cocaine reward. But disulfiram is no cure for addiction; enzyme inhibition by disulfiram as it is understood cannot address the psychosocial and biological underpinnings of addictive behaviors. Nevertheless, clinical trial data and neuropharmacological insights from disulfiram research enable investigators to make specific hypotheses for best treating the complexity of addiction.

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