Cited by 281Pain Mechanisms and TreatmentsMusculoskeletal pain and rehabilitationPain Management and Treatment

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When pain gets stuck: the evolution of pain chronification and treatment resistance

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Borsook, David, Youssef, Andrew M., Simons, Laura, Elman, Igor, Eccleston, Christopher·2018·Pain

DOI 10.1097/j.pain.0000000000001401PMC PMC6240430

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Abstract

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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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
ORCID: Borsook, David
Youssef, Andrew M.
Simons, Laura
Elman, Igor
Eccleston, Christopher
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2018-09-17
Volume: 159
Issue: 12
Pages: 2421-2436
ISSN: 0304-3959 (ISSN-L)
1872-6623
DOI: 10.1097/j.pain.0000000000001401
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

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When pain gets stuck: the evolution of pain chronification and treatment resistance

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