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Phosphorylation: a molecular switch in opioid tolerance

Zaijie Jim Wang1, Lili X Wang

  • 1Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, IL 60612, USA. zjwang@uic.edu

Life Sciences
|July 13, 2006
PubMed

Insights

Protein phosphorylation by kinases like PKC and PKA is crucial for opioid tolerance. Targeting these kinases may help improve pain relief by reducing tolerance to opioids.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Pharmacology

Background:

  • Protein phosphorylation is a critical posttranslational modification regulating protein function.
  • Opioid tolerance, a major clinical challenge, is increasingly linked to specific kinase pathways.

Purpose of the Study:

  • To review recent findings on the role of major protein kinases in opioid tolerance.
  • To highlight the potential of targeting these kinases for improved opioid analgesia.

Main Methods:

  • Literature review of studies investigating protein kinases and opioid tolerance.
  • Focus on protein kinase C (PKC), PKA, CaMKII, PKG, and GRK.

Main Results:

  • Several protein kinases, including PKC, PKA, CaMKII, PKG, and GRK, are implicated in promoting and maintaining opioid tolerance.
  • These kinases function as molecular switches regulating the development of tolerance.

Conclusions:

  • Protein kinase activity is central to the mechanisms underlying opioid tolerance.
  • Pharmacological targeting of these kinases and phosphatases offers a promising strategy to enhance opioid efficacy and manage pain.

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