Editorial review (thematic issue: An update on central sensitivity syndromes and the issues of nosology and psychobiology)
Abstract
Central sensitization (CS), simply defined as an amplified response of the central nervous system to peripheral input, is a concept of great importance in clinical medicine. It has helped to explain aspects of the pathophysiology of common diseases, e.g. fibromyalgia syndrome (FMS), irritable bowel syndrome, vulvodynia, headaches, chronic pelvic pain and other overlapping conditions (collectively called central sensitivity syndromes, or CSS). It also applies to pain of complex regional pain syndrome, osteoarthritis (OA), rheumatoid arthritis (RA) and post-operative pain. The pathology-pain gap in CSS is readily explained by CS. Many FMS and other CSS patients have peripheral pathology, e.g. nociceptive areas in the muscles, arthritis, small fiber neuropathy and inflammation. Pro-inflammatory cytokines are elevated in some patients. Identification of CS in patients with structural pathology, e.g. OA and RA, has helped to explain why not all patients benefit from nonsteroidal anti-inflammatory drugs or joint replacement surgery, and require therapy directed at CS. Glial cells are important in pain processing. Remarkable advances have been achieved in neuroimaging, including visualization of grey matter and white matter, not only during provoked pain but also pain at rest. Based on CS mechanisms, targeted individual therapy may now be possible. Appropriate nosology is important particularly for effective patient care. Dichotomy of neurochemical-structural ("functional") and structural ("organic") pathology should be abandoned; many patients have both. Psychobiology is also biology. Patient-blaming terms like somatization, somatizer and catastrophizing should be avoided. For therapy, both pharmacological and non- pharmacological approaches are important, including recognition of subgroups and person/patient-centered care.
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The similarity in widespread hypersensitivity between irritable bowel syndrome patients and central pain sensitization syndromes such as fibromyalgia led to the view that irritable bowel syndrome is another central sensitization syndrome.
“Against this background, the similarity in widespread hypersensitivity between IBS patients and CPCS, such as FMS, led to the view that IBS is another CCS [10,11].”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [11]
There is wide agreement that fibromyalgia syndrome should be considered a central pain sensitization syndrome.
“Although it is not clear how these physiologic alterations are generated, there is a wide agreement that FMS should be considered as a CPSS [9,10,11,32,33,34].”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [11]
According to Yunus's classification, central sensitization syndromes that involve the experience of chronic pain can be considered central pain sensitization syndromes.
“According to the classification developed by M. B. Yunus on central sensitization syndromes (2007; 2009; 2015), those that involve the experience of chronic pain could be considered as CPSS [9,10,11].”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [11]
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“Until now, SSS was not included in CSS (Yunus, 2015), but our study clearly shows that SSS may be included in the list.”
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Treatment with Adenosine Receptor Agonist Ameliorates Pain Induced by Acute and Chronic Inflammation
Montes, G. C., Hammes, N., da Rocha, M. D., Montagnoli, T. L., Fraga, C. A. M., Barreiro, E. J., Sudo, R. T., & Zapata‐Sudo, G. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.231241 · Cited by 21 · see citing works
“Several studies have correlated high tissue levels of TNF-a with the pain and hyperalgesia associated with a number of diseases (Barnes et al., 1992; Shafer et al., 1994; Tak et al., 1997; Lindenlaub and Sommer, 2003; Uceyler et al., 2015; Yunus, 2015).”
BackgroundNystrom, N., & Freeman, M. D. (2018) · Pain medicine (Malden, Mass.) · doi:10.1093/pm/pnx014 · Cited by 17 · see citing works
Metabolomics in Central Sensitivity Syndromes
Miller, J. S., RODRIGUEZ‐SAONA, L. E., & Hackshaw, K. V. (2020) · Metabolites · doi:10.3390/metabo10040164 · Cited by 22 · see citing works
Haruyama, Y., Sairenchi, T., Uchiyama, K., Suzuki, K., Hirata, K., & Kobashi, G. (2021) · Scientific Reports · doi:10.1038/s41598-021-02678-1 · Cited by 20 · see citing works
Melatonin as a Coadjuvant in the Treatment of Patients with Fibromyalgia
González, D., López‐Pingarrón, L., Castaño, M. Y., Gómez, M. Á., Rodríguez, A. B., García, J. J., & Garrido, M. (2023) · Biomedicines · doi:10.3390/biomedicines11071964 · Cited by 21 · see citing works
Common Pediatric Pain Disorders and Their Clinical Associations
Donnelly, T. J., Bott, A., Bui, M., Goh, S., Jaaniste, T., Chapman, C., Crawford, M., Hopper, J. L., & Champion, G. D. (2017) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000496 · Cited by 20 · see citing works
Hesselink, J. K., Kopsky, D. J., & Sajben, N. L. (2016) · Journal of Pain Research · doi:10.2147/jpr.s115407 · Cited by 20 · see citing works
Persistent dentoalveolar pain disorder: A putative intraoral chronic overlapping pain condition
Babiloni, A. H., Nixdorf, D. R., & Moana-Filho, E. J. (2019) · Oral Diseases · doi:10.1111/odi.13248 · Cited by 20 · see citing works
“…bowel syndrome (IBS), vulvodynia, myalgic encephalomyelitis/chronic fatigue syndrome, bladder pain syndrome/ interstitial cystitis (BPS/IC), endometriosis, chronic tension-type headache, migraine headache, and chronic lower back pain (Maixner et al., 2016; Wessely et al., 1999; Yunus, 2007a, 2015).”
BackgroundAssessing our approach to diagnosing Fibromyalgia
Hackshaw, K. V. (2020) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2020.1858054 · Cited by 19 · see citing works
Adam, F., Jouët, P., Sabaté, J., Perrot, S., Franchisseur, C., Attal, N., & Bouhassira, D. (2022) · Pain · doi:10.1097/j.pain.0000000000002749 · Cited by 16 · see citing works
Olfactory-Related Quality of Life in Multiple Chemical Sensitivity: A Genetic-Acquired Factors Model
Micarelli, A., Cormano, A., Caccamo, D., & Alessandrini, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010156 · Cited by 18 · see citing works
Carracedo, G., Villa-Collar, C. C., Martín‐Gil, A., Serramito, M., & Santamaría, L. (2017) · Eye & Contact Lens Science & Clinical Practice · doi:10.1097/icl.0000000000000416 · Cited by 19 · see citing works
General health status of a sample of patients with burning mouth syndrome: A case–control study
de Pedro, M., López‐Pintor, R. M., Casañas, E., & Hernández, G. (2020) · Oral Diseases · doi:10.1111/odi.13327 · Cited by 18 · see citing works
Proinflammatory cytokines and their receptors as druggable targets to alleviate pathological pain
Kalpachidou, T., Riehl, L., Schöpf, C. L., Uçar, B., & Kress, M. (2022) · Pain · doi:10.1097/j.pain.0000000000002737 · Cited by 17 · see citing works
Løke, D., Løvstad, M., Anđelić, N., Andersson, S., Ystrøm, E., & Vassend, O. M. (2022) · Health Psychology and Behavioral Medicine · doi:10.1080/21642850.2022.2033121 · Cited by 18 · see citing works
“Central sensitization has been closely linked with stress dysregulation and psychological distress (Yunus, 2007), although it is unlikely that central sensitization in isolation can explain the development and exacerbation of fatigue (Yunus, 2015).”
BackgroundWilliams, Z. J., Suzman, E., & Woynaroski, T. G. (2021) · American Journal of Audiology · doi:10.1044/2021_aja-20-00209 · Cited by 16 · see citing works
“30 • 341–358 • June 2021 and vertigo, potentially indicating that these processes may arise from the pathologic process of central sensitization thought to underlie functional somatic syndromes (den Boer et al., 2019; La Touche et al., 2018; Suhnan et al., 2017; Yunus, 2015).”
BackgroundLoria‐Kohen, V., Marcos-Pasero, H., de la Iglesia, R., et al. (2017) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2017.01.030 · Cited by 16 · see citing works
Williams, Z. J., Cascio, C. J., & Woynaroski, T. G. (2022) · Autism · doi:10.1177/13623613221085364 · Cited by 18 · see citing works
“…in pain ratings in autistic adults may be disproportionately affected by the presence of so-called Central Sensitivity Syndromes (CSS), such as fibromyalgia and irritable bowel syndrome (Yunus, 2015), the severity of which can be greatly influenced by psychosocial stressors (Alok et al., 2014).”
BackgroundCentral sensitisation pain and autonomic deficiencies in fibromyalgia
Hernández, A., de la Coba, P., & del Paso, G. A. R. (2022) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/n280oi · Cited by 18 · see citing works
Translation and cross-cultural adaptation of the Polish Central Sensitization Inventory
Turczyn, P., Kosińska, B., Janikowska-Hołoweńko, D., Malec‐Milewska, M., Marszalec, N., Maleszka, P., & Tarnacka, B. (2019) · Reumatologia/Rheumatology · doi:10.5114/reum.2019.86422 · Cited by 15 · see citing works
Selected pathobiological features and principles of pharmacological pain management
Khammissa, R. A. G., Ballyram, R., Fourie, J., Bouckaert, M., Lemmer, J., & Feller, L. (2020) · Journal of International Medical Research · doi:10.1177/0300060520903653 · Cited by 14 · see citing works
Rethinking the criteria for fibromyalgia in 2019: the ABC indicators
Stewart, J. A., Mailler-Burch, S., Müller, D., Studer, M., von Känel, R., Holtforth, M. G., Schwegler, K., & Egloff, N. (2019) · Journal of Pain Research · doi:10.2147/jpr.s205299 · Cited by 14 · see citing works
- Authors
- Yunus, M.
- Corresponding author
- Yunus, Muhammad
- Venue
- Current Rheumatology Reviews
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-07-02
- Volume
- 11
- Issue
- 2
- Pages
- 70-85
- ISSN
- 1573-3971 (ISSN-L)
- OpenAlex
- W843849817
- Cited by
- 226
- References
- 0
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 29 · 2021: 33 · 2020: 19 · 2019: 21 · 2018: 24 · 2017: 31 · 2016: 19 · 2015: 2
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Rheumatology Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- central sensitization, central sensitivity syndromes, fibromyalgia, irritable bowel syndrome, vulvodynia, chronic pelvic pain, complex regional pain syndrome, osteoarthritis, rheumatoid arthritis, postoperative pain, inflammatory cytokines, glial cells, neuroimaging, disease classification, psychobiology, somatization, catastrophizing, person-centred care, pain pathophysiology
- MeSH terms
- Animals, Disease Models, Animal, Humans, Central Nervous System Sensitization, Chronic Pain, Pain Management, Neuroimaging
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