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Towards a theory of chronic pain
Open accessAbstract
In this review, we integrate recent human and animal studies from the viewpoint of chronic pain. First, we briefly review the impact of chronic pain on society and address current pitfalls of its definition and clinical management. Second, we examine pain mechanisms via nociceptive information transmission cephalad and its impact and interaction with the cortex. Third, we present recent discoveries on the active role of the cortex in chronic pain, with findings indicating that the human cortex continuously reorganizes as it lives in chronic pain. We also introduce data emphasizing that distinct chronic pain conditions impact on the cortex in unique patterns. Fourth, animal studies regarding nociceptive transmission, recent evidence for supraspinal reorganization during pain, the necessity of descending modulation for maintenance of neuropathic behavior, and the impact of cortical manipulations on neuropathic pain is also reviewed. We further expound on the notion that chronic pain can be reformulated within the context of learning and memory, and demonstrate the relevance of the idea in the design of novel pharmacotherapies. Lastly, we integrate the human and animal data into a unified working model outlining the mechanism by which acute pain transitions into a chronic state. It incorporates knowledge of underlying brain structures and their reorganization, and also includes specific variations as a function of pain persistence and injury type, thereby providing mechanistic descriptions of several unique chronic pain conditions within a single model.
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“As stated by Apkarian et al, 7 the transition from acute to chronic pain entails also a transition in the salience of pain, wherein the condition shifts from viewing a painful percept as a sign of external threat into an indication of an internalized disease state.”
From Pain and Evil: From Local Nociception to Misery Following Social Harm (2020) · cites this paper as [7]
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Metadata
- Authors
- Apkarian, A. V., Baliki, M. N., & Geha, P. Y.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Apkarian, A. Vania
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 87
- Issue
- 2
- Pages
- 81-97
- ISSN
- 0301-0082 (ISSN-L)
- PMC
- PMC2650821
- OpenAlex
- W1995458911
- Cited by
- 876
- References
- 151
- Citations by year
- 2026: 62 · 2025: 57 · 2024: 41 · 2023: 28 · 2022: 35 · 2021: 51 · 2020: 46 · 2019: 53 · 2018: 48 · 2017: 65 · 2016: 55 · 2015: 47 · 2014: 68 · 2013: 57 · 2012: 59
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 57704, R21NS053602, NS35115, NS53602, R01NS057704, R01NS035115)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- chronic pain, nociception, descending pain modulation, neuropathic pain, cortical reorganization, acute to chronic pain transition, pain mechanisms, pharmacological pain management
- MeSH terms
- Animals, Brain, Brain Mapping, Chronic Disease, Humans, Pain, Pain Management
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