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Kappa opioids and the modulation of pain

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Abstract

Background and rationale

Pain is a complex sensory experience, involving cognitive factors, environment (setting, society, and culture), experience, and gender and is modulated significantly by the central nervous system (CNS). The mechanisms by which opioid analgesics work are understood, but this class of drugs is not ideal as either an analgesic or anti-hyperalgesic. Accordingly, considerable effort continues to be directed at improved understanding of nociceptor function and development of selective analgesics that do not have the unwanted effects associated with opioid analgesics.

Objective

The purpose of this paper is to provide a review of the role of KOP receptors in the modulation of pain and highlight several chemotypes currently being explored as peripherally restricted KOP ligands.

Results

A growing body of literature has shown that KOP receptors are implicated in a variety of behavioral pain models. Several different classes of peripherally restricted peptidic and nonpeptidic KOP agonists have been identified and show utility in treating painful conditions.

Conclusion

The pharmacological profile of KOP agonists in visceral pain models suggest that peripherally restricted KOP agonists are potentially useful for a variety of peripheral pain states. Further, clinical investigation of peripherally restricted KOP agonists will help to clarify the painful conditions where KOP agonists will be most effective.

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Abbreviations

KOP:

κ opioid

MOP:

μ opioid

CNS:

Central nervous system

COX:

Cyclooxygenase

PAG:

Periaqueductal gray

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Authors and Affiliations

  1. School of Biological Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand

    Bronwyn Kivell

  2. Department of Medicinal Chemistry, School of Pharmacy, University of Kansas, 1251 Wescoe Hall Drive, 4070 Malott Hall, Lawrence, KS, 66045-7582, USA

    Thomas E. Prisinzano

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  1. Bronwyn Kivell
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Correspondence to Thomas E. Prisinzano.

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Kivell, B., Prisinzano, T.E. Kappa opioids and the modulation of pain. Psychopharmacology 210, 109–119 (2010). https://doi.org/10.1007/s00213-010-1819-6

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