New approaches to study the development of morphine tolerance and dependence

Hiroshi Ueda, Makoto Inoue, Kiyonobu Mizuno

Research output: Contribution to journalArticlepeer-review

Abstract

Morphine is now believed not to cause tolerance and dependence when it is appropriately used in clinic. However, in terminal cancer pain, patients' analgesic tolerance to morphine is developed due to the use of high doses of morphine for complete blockade of pain. At higher doses, morphine has more opportunity to show serious side effects, which worsens quality of life (QOL), and leads to the use of potent analgesic adjuvants to reduce the morphine dosage. Here we attempt to summarize recent studies of the molecular basis of morphine tolerance and dependence, and to discuss whether these mechanisms could provide new molecular targets as analgesic adjuvants. They include protein kinase C inhibitor, opioid agonist with low RAVE value, and antagonists of antiopioid receptors (GluRε1 or nociceptin/OFQ receptor). In addition, we demonstrate new approaches to find further candidates of such molecular targets. These approaches include the visualization of neuronal networks in the downstream of opioid neurons by use of the WGA transgene technique and the single cell dissection technique to get new genes involved in plasticity during morphine tolerance and dependence.

Original languageEnglish (US)
Pages (from-to)313-320
Number of pages8
JournalLife Sciences
Volume74
Issue number2-3
DOIs
StatePublished - Dec 5 2003
Externally publishedYes

Keywords

  • Antiopioid
  • NMDA receptor
  • Nociceptin
  • WGA transgene

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'New approaches to study the development of morphine tolerance and dependence'. Together they form a unique fingerprint.

Cite this