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Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction

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The Kappa Opioid Receptor

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 271))

Abstract

Pain is complex and is a unique experience for individuals in that no two people will have exactly the same physiological and emotional response to the same noxious stimulus or injury. Pain is composed of two essential processes: a sensory component that allows for discrimination of the intensity and location of a painful stimulus and an emotional component that underlies the affective, motivational, unpleasant, and aversive response to a painful stimulus. Kappa opioid receptor (KOR) activation in the periphery and throughout the neuroaxis modulates both of these components of the pain experience. In this chapter we focus on recent findings that KORs contribute to the emotional, aversive nature of chronic pain, including how expression in the limbic circuitry contributes to anhedonic states and components of opioid misuse disorder. While the primary focus is on preclinical pain models, we also highlight clinical or human research where there is strong evidence for KOR involvement in negative affective states associated with chronic pain and opioid misuse.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

BLA:

Basolateral amygdala

BNST:

Bed nucleus of the stria terminalis

CeA:

Central nucleus of the amygdala

CPA:

Conditioned place aversion

CPP:

Conditioned place preference

CRF:

Corticotropin-releasing hormone

DOR:

Delta opioid receptor

GABA:

Gamma-aminobutyric acid

GPCRs:

G-protein coupled receptors

ICSS:

Intracranial self-stimulation

JDTic:

C28H39N3O3 kappa opioid antagonist

KOR:

Kappa opioid receptor

LiCl:

Lithium chloride

MAP:

Mitogen-activated protein

MK801:

Dizocilpine, NMDA antagonist

MOR:

Mu opioid receptor

nor-BNI:

Nor-binaltorphimine, kappa opioid antagonist

NMDA:

Nucleus accumbens NAc

ORL1:

Opioid receptor-like/nociceptin receptor

PAG:

Periaqueductal gray

VTA:

Ventral tegmental area

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Acknowledgements

Funding: The Shirley Hatos Foundation supports CMC, CJE, and LL. NIH Grant numbers R01DA041781 (CMC), 1UG3TR003148-01 (CMC), and 2P50 DA005010 (CMC, CJE), and the Department of Defense Grant number W81XWH-15-1-0435 (CMC).

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Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA

    Catherine M. Cahill, Lindsay Lueptow & Christopher J. Evans

  2. Shirley and Stefan Hatos Center for Neuropharmacology, University of California Los Angeles, Los Angeles, CA, USA

    Catherine M. Cahill, Lindsay Lueptow, Hannah Kim, Raj Shusharla, Amy Bishop & Christopher J. Evans

  3. Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA

    Catherine M. Cahill & Christopher J. Evans

  4. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Catherine M. Cahill & Christopher J. Evans

  5. Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA

    Lindsay Lueptow & Christopher J. Evans

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  1. Catherine M. Cahill
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  2. Lindsay Lueptow
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  3. Hannah Kim
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  4. Raj Shusharla
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  5. Amy Bishop
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  6. Christopher J. Evans
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Correspondence to Catherine M. Cahill .

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Editors and Affiliations

  1. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Lee-Yuan Liu-Chen

  2. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Saadet Inan

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Cahill, C.M., Lueptow, L., Kim, H., Shusharla, R., Bishop, A., Evans, C.J. (2021). Kappa Opioid Signaling at the Crossroads of Chronic Pain and Opioid Addiction. In: Liu-Chen, LY., Inan, S. (eds) The Kappa Opioid Receptor. Handbook of Experimental Pharmacology, vol 271. Springer, Cham. https://doi.org/10.1007/164_2021_434

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