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When pain gets stuck: the evolution of pain chronification and treatment resistance
Open accessAbstract
It is well-recognized that, despite similar pain characteristics, some people with chronic pain recover, whereas others do not. In this review, we discuss possible contributions and interactions of biological, social, and psychological perturbations that underlie the evolution of treatment-resistant chronic pain. Behavior and brain are intimately implicated in the production and maintenance of perception. Our understandings of potential mechanisms that produce or exacerbate persistent pain remain relatively unclear. We provide an overview of these interactions and how differences in relative contribution of dimensions such as stress, age, genetics, environment, and immune responsivity may produce different risk profiles for disease development, pain severity, and chronicity. We propose the concept of "stickiness" as a soubriquet for capturing the multiple influences on the persistence of pain and pain behavior, and their stubborn resistance to therapeutic intervention. We then focus on the neurobiology of reward and aversion to address how alterations in synaptic complexity, neural networks, and systems (eg, opioidergic and dopaminergic) may contribute to pain stickiness. Finally, we propose an integration of the neurobiological with what is known about environmental and social demands on pain behavior and explore treatment approaches based on the nature of the individual's vulnerability to or protection from allostatic load.
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“People are oNen rigidly held in unhelpful patterns of behaviour that substantially increase their risk of over-treatment, multi-morbidity and mortality (Borsook 2018).”
From Psychological therapies for the management of chronic pain (excluding headache) in adults (2020) · cites this paper as Borsook 2018
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“Several emotional distress factors are regarded as mediators in the “chronification” of pain, that is, persistent pain with characteristic pain behavior and resistance to therapeutic intervention (Borsook et al., 2018). These factors include pain catastrophizing, anxiety, and fear of pain and helplessness (Keefe et al., 2004).”
From The Development of Mindful-Based Dance Movement Therapy Intervention for Chronic Pain: A Pilot Study With Chronic Headache Patients (2021) · cites this paper as Borsook et al., 2018
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Metadata
- Authors
- Borsook, D., Youssef, A. M., Simons, L., Elman, I., & Eccleston, C.
- Affiliations
- Boston Children's Hospital (US)
- Stanford University (US)
- United States Department of Veterans Affairs (US)
- Ghent University (BE)
- Corresponding author
- Borsook, David
- Venue
- Pain
- Published
- 2018-09-17
- Volume
- 159
- Issue
- 12
- Pages
- 2421-2436
- ISSN
- 0304-3959 (ISSN-L)
- 1872-6623
- PMC
- PMC6240430
- OpenAlex
- W2895537149
- Cited by
- 281
- References
- 291
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 30 · 2023: 85 · 2022: 28 · 2021: 34 · 2020: 32 · 2019: 12 · 2018: 2
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K24NS064050)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD083133)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- chronic pain, pain chronification, treatment resistance, stress, genetic susceptibility, opioid system, dopaminergic system, artificial neural networks, allostatic load, pain behavior
- MeSH terms
- Animals, Brain, Drug Resistance, Humans, Neurobiology, Socioeconomic Factors, Genetic Predisposition to Disease, Illness Behavior, Chronic Pain
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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