title: Does the kappa opioid receptor system contribute to pain aversion?
abstract: The kappa opioid receptor (KOR) and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California Irvine Irvine, CA, USA ; Department of Pharmacology, University of California Irvine Irvine, CA, USA ; Department of Biomedical and Molecular Sciences, Queen's University Kingston, ON, Canada.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cahill
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California Irvine Irvine, CA, USA ; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles Los Angeles, CA, USA.
authors.forename: Anna M W
authors.initials: AM
authors.lastname: Taylor
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California Irvine Irvine, CA, USA ; Department of Pharmacology, University of California Irvine Irvine, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cook
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California Irvine Irvine, CA, USA ; Department of Biomedical and Molecular Sciences, Queen's University Kingston, ON, Canada.
authors.forename: Edmund
authors.initials: E
authors.lastname: Ong
authors.affiliation: Department of Anesthesiology, Columbia University Medical Center, New York, NY USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Morón
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles Los Angeles, CA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Evans
keywords: aversion; dopamine; kappa opioid receptor; negative reinforcement; pain; reward system ventral tegmental area