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Cited by 215Opioid Use Disorder TreatmentPain Management and Opioid UseAnesthesia and Pain Management

Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain

Open access
Shurman, Joseph, Koob, George F., Gutstein, Howard B.·2010·Pain Medicine
DOI 10.1111/j.1526-4637.2010.00881.xPMC PMC2907890
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Abstract

OBJECTIVE: Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. RESULTS: In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). CONCLUSIONS: Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

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  • Hyperkatifeia can be considered an emotional parallel to hyperalgesia observed with repeated administration of chronic opioids and alcohol.

    “Hyperkatifeia can be considered an emotional parallel to hyperalgesia (i.e., greater sensitivity to physical pain) that is observed with repeated administration of chronic opioids and alcohol (Shurman et al., 2010;Koob, 2019).”

    From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Shurman et al., 2010

    The Introduction describes hyperkatifeia as hypersensitivity to emotional distress, analogous to hyperalgesia as hypersensitivity to pain. It links both to excessive opioid exposure that disrupts homeostasis, but says they are less likely when opioids effectively relieve pain. Our copy does not extend this pairing to repeated alcohol administration. (LLM, conf=0.86)

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  • Neurocircuitry dysregulations contribute to links between neural mechanisms of hyperkatifeia and hyperalgesia.

    “The argument is that these specific neurocircuitry dysregulations contribute to the links that have been hypothesized to exist between the neural mechanisms that are responsible for hyperkatifeia and hyperalgesia (Shurman et al., 2010;Koob, 2019).”

    From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Shurman et al., 2010

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Research works printed but not linked: 2

  1. [20]Gustein HB Akil H Brunton LL Lazo JS Parker KL Opioid analgesics Goodman and Gilman’s The Pharmacological Basis of Therapeutics 11th New York McGraw-Hill 2006 547 90
  2. [26]Koob GF Everitt BJ Robbins TW Squire LG Berg D Bloom FE Reward, motivation, and addiction Fundamental Neuroscience 3 Amsterdam Academic Press 2008 987 1016

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Authors
Shurman, J., Koob, G. F., & Gutstein, H. B.
Affiliations
  • Scripps Memorial Hospital (US)
  • Scripps Research Institute (US)
  • The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Koob, George F.
ORCID
Venue
Pain Medicine
Publisher
Oxford University Press (OUP)
Published
2010-07
Volume
11
Issue
7
Pages
1092-1098
ISSN
  • 1526-2375 (ISSN-L)
  • 1526-4637
DOI
10.1111/j.1526-4637.2010.00881.x
PMC
PMC2907890
OpenAlex
W1730875209
Cited by
215
References
24
Citations by year
2026: 10 · 2025: 14 · 2024: 16 · 2023: 12 · 2022: 16 · 2021: 22 · 2020: 43 · 2019: 17 · 2018: 13 · 2017: 8 · 2016: 11 · 2015: 7 · 2014: 8 · 2013: 10 · 2012: 5
FWCI
5.64
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1 (tdm, 1888 d)
Locations
  • Pain Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism (R01AA016157, AA16157)
  • National Institute on Drug Abuse (DA04043, DA 15146, R01DA015146, R01DA004043)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
  • Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
Keywords
opioids, opioid misuse, opioid use disorder, pain management, opponent processes, reward systems, stress system, emotional distress, opioid withdrawal, hyperalgesia, homeostasis, opioid overdose
MeSH terms
Analgesics, Opioid, Brain, Emotions, Homeostasis, Humans, Hyperalgesia, Opioid-Related Disorders, Pain, Stress, Psychological

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