Antidepressants as analgesics: An overview of central and peripheral mechanisms of action

J. Sawynok, M. J. Esser, A. R. Reid

Research output: Contribution to journalArticlepeer-review

203 Citations (Scopus)

Abstract

Antidepressants, given systemically, are widely used for the treatment of various chronic and neuropathic pain conditions in humans. In animal studies, antidepressants exhibit analgesic properties in nociceptive, inflammatory and neuropathic test systems, with outcomes depending on the specific agent, the particular test, the route of administration and the treatment method used. Although early studies focused on central (i.e., supraspinal, spinal) actions, more recent studies have demonstrated a local peripheral analgesic effect of antidepressants. These peripheral actions raise the possibility that topical formulations of antidepressants may be a useful alternative drug delivery system for analgesia. Antidepressants exhibit a number of pharmacological actions: they block reuptake of noradrenaline and 5-hydroxytryptamine, have direct and indirect actions on opioid receptors, inhibit histamine, cholinergic, 5-hydroxytryptamine and N-methyl-D-aspartate receptors, inhibit ion channel activity, and block adenosine uptake. The involvement of these mechanisms in both central and peripheral analgesia produced by antidepressants is considered. Data illustrating the preclinical peripheral analgesic actions of antidepressants are presented, as are some aspects of the mechanisms by which these actions occur.

Original languageEnglish
Pages (from-to)21-29
Number of pages9
JournalJournal of Psychiatry and Neuroscience
Volume26
Issue number1
Publication statusPublished - 2001

ASJC Scopus Subject Areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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