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The downward spiral of chronic pain, prescription opioid misuse, and addiction: Cognitive, affective, and neuropsychopharmacologic pathways
Open accessAbstract
Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction.
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“In contrast to other health outcomes, the health-promoting effects of meditation are most pronounced for pain and pain-related comorbidities, including opioid addiction and misuse,155–158 stress,37, 138 depression,159–161 and anxiety.31, 162, 163”
From Mindfulness meditation-based pain relief: a mechanistic account (2016) · cites this paper as [155]
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A default mode of brain function
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.676 · Cited by 12,190
Pain mechanisms: a new theory.
Melzack, R., & Wall, P. D. (1965) · Science · doi:10.1126/science.150.3699.971 · Cited by 11,108
Neural systems of reinforcement for drug addiction: from actions to habits to compulsion
Everitt, B. J., & Robbins, T. W. (2005) · Nature Neuroscience · doi:10.1038/nn1579 · Cited by 3,785
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299
The Self-Medication Hypothesis of Substance Use Disorders: A Reconsideration and Recent Applications
Khantzian, E. J. (1997) · Harvard Review of Psychiatry · doi:10.3109/10673229709030550 · Cited by 3,242
Human brain mechanisms of pain perception and regulation in health and disease
Apkarian, A. V., Bushnell, M. C., Treede, R., & Zubieta, J. (2005) · European Journal of Pain · doi:10.1016/j.ejpain.2004.11.001 · Cited by 3,126
Hölzel, B. K., Lazar, S. W., Gard, T., Schuman-Olivier, Z., Vago, D. R., & Ott, U. (2011) · Perspectives on Psychological Science · doi:10.1177/1745691611419671 · Cited by 3,024
Drug Addiction, Dysregulation of Reward, and Allostasis
Koob, G. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00195-0 · Cited by 2,953
Melzack, R., & Wall, P. D. (1996) · Pain Forum · doi:10.1016/s1082-3174(96)80062-6 · Cited by 2,786
The Neural Basis of Addiction: A Pathology of Motivation and Choice
Kalivas, P. W., & Volkow, N. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.8.1403 · Cited by 2,757
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Collado, A., Welch, S. B., Sambirsky, K., Long, P., & Dimidjian, S. (2026) · Substance Use & Misuse · doi:10.1080/10826084.2026.2679710 · Cited by 1
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Bhatt, S. (2016) · Current Emergency and Hospital Medicine Reports · doi:10.1007/s40138-016-0097-y · Cited by 1
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Haque, M. M. M. (2017) · Insights in Nutrition and Metabolism · doi:10.35841/nutrition-metabolism.1000104
Thomas, C. J., Sambathkumar, R., & Venkateswaramurthy, N. (2021) · Journal of Drug Delivery and Therapeutics · doi:10.22270/jddt.v11i6.5139 · Cited by 1
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Ballantyne, J. C., Sullivan, M. D., & Saxon, A. J. (2025) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000001526 · Cited by 1
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Halman, S., Tran, A., O'Brien, T., & Card, S. E. (2023) · Canadian Medical Education Journal · doi:10.36834/cmej.74949 · Cited by 1
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Wettasinghe, R. (2014) · eScholarship (California Digital Library)
Neuroscientific Changes of Chronic Neuropathic Pain: A Brief Comment on Evidence-Based Practice
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Smith, K. E. (2019) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/3259
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-, S. D., -, N. P., -, A. S., -, S. P., & -, A. R. (2024) · International Journal For Multidisciplinary Research · doi:10.36948/ijfmr.2024.v06i06.31918
Garland, E. L. (2025) · Nature Mental Health · doi:10.1038/s44220-024-00378-z
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Moore, J. R., Choi, N. G., & DiNitto, D. M. (2025) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2025.2577303
Macchia, L., VanderWeele, T. J., & Cowden, R. G. (2025) · Research Square · doi:10.21203/rs.3.rs-7933890/v1
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Luo, Y., Deznabi, I., Gullapalli, B. T., Tuomenoksa, M., Fiterau, M., Garland, E. L., & Rahman, T. (2026) · Nature Mental Health · doi:10.1038/s44220-025-00555-8
Self-citationYip, M.-K., Liu, C.-Y. J., & Poon, W. (2026) · Reports — Medical Cases Images and Videos · doi:10.3390/reports9010017
Childs, K., Minnick, C., Martorella, G., & Hanley, A. W. (2026) · JMIR Research Protocols · doi:10.2196/82362
Brewer, J. R., Lee, P., Levey, N., Ditre, J. W., Chen, N., Mudgal, C., Bhashyam, A. R., Garg, R., Ring, D., Vranceanu, A., et al. (2026) · Pain Management · doi:10.1080/17581869.2026.2660326
Costa, G. P. A., Riggione, C., Meyerovich, J., Barry, D. T., & Aquino, J. P. D. (2026) · American Journal on Addictions · doi:10.1111/ajad.70162
Plasil, S. L., Tieu, L., Qian, C., Taylor, N., Sneddon, E. A., Carrette, L. L. G., Brennan, M., Morgan, A., Othman, D. N., Bai, K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.14.725258
Scott, D., Mutaru, A., Maldonado, I., Junior, H. P. D. O. S., Prado, G. J., & Lozano, A. (2026) · Current Addiction Reports · doi:10.1007/s40429-026-00762-y
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Plasil, S. L., Tieu, L., Qian, C., Taylor, N., Coe, S., Sneddon, E. A., Carrette, L. L. G., Brennan, M., Morgan, A. A., Othman, D. N., et al. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111197
Metadata
- Authors
- Garland, E. L., Froeliger, B., Zeidan, F., Partin, K., & Howard, M. O.
- Affiliations
- University of Utah (US)
- Medical University of South Carolina (US)
- Wake Forest University (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Garland, Eric L.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 37
- Issue
- 10
- Pages
- 2597-2607
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC3967721
- OpenAlex
- W2110728022
- Cited by
- 277
- References
- 189
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 16 · 2023: 21 · 2022: 25 · 2021: 27 · 2020: 47 · 2019: 28 · 2018: 12 · 2017: 22 · 2016: 17 · 2015: 14 · 2014: 15
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Fahs-Beck Fund for Research and Experimentation
- 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 › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- chronic pain, prescription opioid misuse, opioid use disorder, downward spiral, opioid analgesia, negative affect, opioid-dopamine interaction, drug cue reactivity, cognitive control network, mindfulness-based interventions, multimodal therapy
- MeSH terms
- Analgesics, Opioid, Cognition Disorders, Humans, Opioid-Related Disorders, Mood Disorders, Chronic Pain, Prescription Drug Misuse
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