Antinociceptive and nociceptive actions of opioids

Michael H. Ossipov, Josephine Lai, Tamara King, Todd W. Vanderah, T. Philip Malan, Victor J. Hruby, Frank Porreca

Research output: Contribution to journalReview articlepeer-review

217 Scopus citations

Abstract

Although the opioids are the principal treatment options for moderate to severe pain, their use is also associated with the development of tolerance, defined as the progressive need for higher doses to achieve a constant analgesic effect. The mechanisms which underlie this phenomenon remain unclear. Recent studies revealed that cholecystokinin (CCK) is upregulated in the rostral ventromedial medulla (RVM) during persistent opioid exposure. CCK is both antiopioid and pronociceptive, and activates descending pain facilitation mechanisms from the RVM enhancing nociceptive transmission at the spinal cord and promoting hyperalgesia. The neuroplastic changes elicited by opioid exposure reflect adaptive changes to promote increased pain transmission and consequent diminished antinociception (i.e., tolerance).

Original languageEnglish (US)
Pages (from-to)126-148
Number of pages23
JournalJournal of Neurobiology
Volume61
Issue number1
DOIs
StatePublished - Oct 2004

Keywords

  • Antinociception
  • Nociception
  • Opioids

ASJC Scopus subject areas

  • General Neuroscience
  • Cellular and Molecular Neuroscience

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