Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing
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The current study tested the hypothesis that conditioned pain modulation is mediated by the release of endogenous opioids with a placebo-controlled (sugar pill) study of naltrexone (50 mg) in 33 healthy volunteers over two counter-balanced sessions. Pain modulation consisted of rating of heat pain (palm) during concurrent cold water immersion (foot). Compared to baseline heat pain ratings, concurrent foot immersion lowered pain intensity ratings, which suggests an inhibitory effect, was reduced with naltrexone, suggesting at least partial dependence of inhibition on endogenous opioids. An exploratory analysis revealed that individual differences in catastrophizing moderated the effects of naltrexone; endogenous opioid blockade abolished modulation in subjects lower in catastrophizing while modulation was unaffected by naltrexone among high catastrophizers. The results suggest a role of endogenous opioids in endogenous analgesia, but hint that multiple systems might contribute to conditioned pain modulation, and that these systems might be differentially activated as a function of individual differences in responses to pain.
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Pain relief produced by conditioned pain modulation is reversed by naloxone.
“Pain relief produced by placebo (Levine et al., 1978;Grevert et al., 1983;Amanzio and Benedetti, 1999;Zubieta et al., 2005;Eippert et al., 2009), conditioned pain modulation (King et al., 2013), and attentional control (Sprenger et al., 2012) is reversed by administration of the opioid antagonist naloxone.”
From Mindfulness-meditation-based pain relief is not mediated by endogenous opioids (2016) · cites this paper as King et al., 2013
The Discussion reports that CPM-related pain inhibition was blocked by naltrexone, the antagonist tested in this study. The Introduction and Discussion describe mixed findings for naloxone in other CPM studies, so this source does not establish that naloxone reverses CPM pain relief. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPain relief produced by placebo, acupuncture, conditioned pain modulation, distraction, and hypnosis is mediated, in part, by endogenous opioidergic systems.
“Pain relief produced by placebo,2,34,47,67,147 acupuncture,51 conditioned pain modulation,61 distraction,108 and hypnosis39,110 is meditated, in part, by endogenous opioidergic systems.”
From The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer (2019) · cites this paper as [61]
Analgesia from placebo, conditioned pain modulation, acupuncture, hypnosis, and attentional control is mediated by endogenous opioid mechanisms.
“Endogenous opioidergic mechanisms have been repeatedly demonstrated to mediate analgesia produced by placebo,89–93 conditioned pain modulation,94 acupuncture,95 hypnosis,96 and attentional control.97”
From Mindfulness meditation-based pain relief: a mechanistic account (2016) · cites this paper as [94]
Cognitive pain modulation from placebo, conditioned pain modulation, and attentional control partly depends on descending pain control and can be blocked by naloxone.
“it is well established that the cognitive modulation of pain, including manipulations such as placebo89, 91–93, 105, 145, conditioned pain modulation,94 and attentional control,97 is partially dependent on descending pain control systems98, 146 and can be reversed by the opioid antagonist naloxone.90, 91, 97, 147”
From Mindfulness meditation-based pain relief: a mechanistic account (2016) · cites this paper as [94]
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- Authors
- King, C. D., Goodin, B., Kindler, L. L., Caudle, R. M., Edwards, R. R., Gravenstein, N., Riley, J. L., & Fillingim, R. B.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- King, Christopher D.
- ORCID
- Venue
- Journal of Behavioral Medicine
- Published
- 2012-04-26
- Volume
- 36
- Issue
- 3
- Pages
- 315-327
- ISSN
- 0160-7715 (ISSN-L)
- 1573-3521
- PMC
- PMC3774309
- OpenAlex
- W2075636049
- Cited by
- 79
- References
- 94
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 11 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 6 · 2013: 8
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Behavioral Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR000065, 5r01ag033906-10, UL1TR000064)
- National Institute on Aging (L30 AG040467, R-01-AG-033906, R37AG033906, R01AG034982, P30AG028740)
- National Institute of Neurological Disorders and Stroke (T32NS045551)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR057920)
- National Institute of Dental and Craniofacial Research (T32DE007200)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- conditioned pain modulation, naltrexone, pain catastrophizing, endogenous opioids, endogenous analgesia, placebo effect, thermal pain, cold water immersion, individual differences, opioid blockade
- MeSH terms
- Adult, Conditioning, Classical, Double-Blind Method, Female, Humans, Individuality, Male, Naltrexone, Narcotic Antagonists, Pain, Pain Threshold, Cross-Over Studies, Opioid Peptides, Young Adult, Catastrophization, Diffuse Noxious Inhibitory Control
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