Exploring the underlying mechanism of pain-related disability in hypermobile adolescents with chronic musculoskeletal pain
Open accessAbstract
Objectives: A significant proportion of adolescents with chronic musculoskeletal pain (CMP) experience difficulties in physical functioning, mood and social functioning, contributing to diminished quality of life. Generalized joint hypermobility (GJH) is a risk factor for developing CMP with a striking 35-48% of patients with CMP reporting GJH. In case GJH occurs with one or more musculoskeletal manifestations such as chronic pain, trauma, disturbed proprioception and joint instability, it is referred to as generalized hypermobility spectrum disorder (G-HSD). Similar characteristics have been reported in children and adolescents with the hypermobile Ehlers-Danlos Syndrome (hEDS). In the management of CMP, a biopsychosocial approach is recommended as several studies have confirmed the impact of psychosocial factors in the development and maintenance of CMP. The fear-avoidance model (FAM) is a cognitive-behavioural framework that describes the role of pain-related fear as a determinant of CMP-related disability. Content: Pubmed was used to identify existing relevant literature focussing on chronic musculoskeletal pain, generalized joint hypermobility, pain-related fear and disability. Relevant articles were cross-referenced to identify articles possibly missed during the primary screening. In this paper the current state of scientific evidence is presented for each individual component of the FAM in hypermobile adolescents with and without CMP. Based on this overview, the FAM is proposed explaining a possible underlying mechanism in the relations between GJH, pain-related fear and disability. Summary and outlook: It is assumed that GJH seems to make you more vulnerable for injury and experiencing more frequent musculoskeletal pain. But in addition, a vulnerability for heightened pain-related fear is proposed as an underlying mechanism explaining the relationship between GJH and disability. Further scientific confirmation of this applied FAM is warranted to further unravel the underlying mechanism. In explaining disability in individuals with G-HSD/hEDS, it is important to focus on both the physical components related to joint hypermobility, in tandem with the psychological components such as pain-related fear, catastrophizing thoughts and generalized anxiety.
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The Fear-Avoidance Model has been adapted for HSD and hEDS, highlighting the added challenges of hypermobility, which increase injury risk and exacerbate this cycle.
“The Fear-Avoidance Model has been adapted for HSD and hEDS, highlighting the added challenges of hypermobility, which increase injury risk and exacerbate this cycle.19”
From Role of Anxiety in Individuals with Generalized Joint Hypermobility: A Systematic Review (2025) · cites this paper as [19]
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“Furthermore, children and adolescents with G-HSD/ hEDS report playing more non-sports (such as board games or electronic games) and report needing more time to rest [44].”
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Campayo, J. G., Asso, E., Alda, M., Andrés, E., & Sobradiel, N. (2010) · Psychosomatics · doi:10.1176/appi.psy.51.1.55 · Cited by 47 · cited 1× · see citing works
“Furthermore, an increased incidenceof other psychiatric disorders, including panic disorders [58, 69] and anxiety disorders [67, 68, 70] were found to be associatedwithG-HSD/hEDS.”
BackgroundSohrbeck-Nøhr, O., Kristensen, J. H., Boyle, E., Remvig, L., & Juul-Kristensen, B. (2014) · BMC Pediatrics · doi:10.1186/s12887-014-0302-7 · Cited by 45 · cited 2× · see citing works
“[33] found that GJH had a 3 times higher risk of developing joint pain in adolescence.”
BackgroundEl-Metwally, A., Salminen, J. J., Auvinen, A., Kautiainen, H., & Mikkelsson, M. (2006) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-7-3 · Cited by 44 · see citing works
Baeza-Velasco, C., Sinibaldi, L., & Castori, M. (2018) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-018-0252-2 · Cited by 44 · cited 1× · see citing works
“Furthermore, recent studies showed the potential role of neurodiversity, such as Attention-deficit/hyperactivity disorder (ADHD) and Autism Spectrum Disorders (ASD) in G-HSD/hEDS [85, 86].”
BackgroundScheper, M., de Vries, J., Beelen, A., de Vos, R., Nollet, F., & Engelbert, R. (2015) · Current Rheumatology Reviews · doi:10.2174/1573397111666150120112925 · Cited by 44 · cited 4× · see citing works
“Some studies performed in children and adolescents with asymptomatic GJH indeed showeddecreasedmuscle strength [45, 53] and lower levels of cardiorespiratory fitness [54] compared to nonhypermobile pain-free peers, while other studies could not confirm this [41, 55, 56].”
BackgroundInfluentialSelf-citationJoint hypermobility syndrome subclassification in paediatrics: a factor analytic approach
Pacey, V., Adams, R. D., Tofts, L., Munns, C. F., & Nicholson, L. L. (2015) · Archives of Disease in Childhood · doi:10.1136/archdischild-2013-305304 · Cited by 40 · cited 1× · see citing works
“Studies also showed that exercise-inducedmuscle pain is a distinctive symptom in individuals with G-HSD/hEDS, mostly in the knee and the shoulder [25, 28].”
BackgroundRuemper, A., & Watkins, K. (2012) · Journal of Dance Medicine & Science · doi:10.1177/1089313x1201600403 · Cited by 39 · see citing works
Knee function in 10-year-old children and adults with Generalised Joint Hypermobility.
Juul-Kristensen, B., Hansen, H., Simonsen, E., Alkjær, T., Kristensen, J. H., Jensen, B. R., & Remvig, L. (2012) · Knee (Oxford) · doi:10.1016/j.knee.2012.02.002 · Cited by 38 · cited 1× · see citing works
“Some studies performed in children and adolescents with asymptomatic GJH indeed showeddecreasedmuscle strength [45, 53] and lower levels of cardiorespiratory fitness [54] compared to nonhypermobile pain-free peers, while other studies could not confirm this [41, 55, 56].”
Kleef, Y. B. H.-V., Helders, P., Takken, T., & Engelbert, R. (2009) · Pediatric Physical Therapy · doi:10.1097/pep.0b013e3181a3ac5f · Cited by 35 · cited 1× · see citing works
“In addition, reduced cardiorespiratory fitness has been observed in children and adolescents with G-HSD/hEDS compared to non-hypermobile pain-free peers [51, 52].”
BackgroundSelf-citationNeural and psychosocial mechanisms of pain sensitivity in fibromyalgia.
English, B. M. (2014) · Pain Management Nursing · doi:10.1016/j.pmn.2012.07.009 · Cited by 32 · cited 1× · see citing works
“As a result, pain could occur even in response to non-painful stimuli [31].”
BackgroundHow do people with chronically painful joint hypermobility syndrome make decisions about activity?
Schmidt, A., Corcoran, K., Grahame, R., & Williams, A. C. D. C. (2014) · British Journal of Pain · doi:10.1177/2049463714554112 · Cited by 32 · cited 1× · see citing works
“This finding was confirmed by the results of a qualitative semi-structured interview study [40], in which women with G-HSD reported that fear of pain or re/injury reduced or altered particular activities.”
ResultEfficacy of an out-patient pain management programme for people with joint hypermobility syndrome
Rahman, A., Daniel, C., & Grahame, R. (2014) · Clinical Rheumatology · doi:10.1007/s10067-014-2539-9 · Cited by 26 · cited 1× · see citing works
“[38] performed in adults with G-HSD showed high levels of pain catastrophizing (average PCS score of 27.”
BackgroundHuijnen, I., Verbunt, J., Wittink, H., & Smeets, R. (2013) · European Journal of Physiotherapy · doi:10.3109/21679169.2013.830643 · Cited by 25 · cited 1× · see citing works
“Individuals might decide to stop or perform submaximally, resulting in a lower score [50].”
BackgroundSelf-citationvan Meulenbroek, T., Huijnen, I. P. J., Stappers, N. E. H., Engelbert, R., & Verbunt, J. (2020) · Physiotherapy Theory and Practice · doi:10.1080/09593985.2019.1709231 · Cited by 19 · cited 3× · see citing works
“Some studies performed in children and adolescents with asymptomatic GJH indeed showeddecreasedmuscle strength [45, 53] and lower levels of cardiorespiratory fitness [54] compared to nonhypermobile pain-free peers, while other studies could not confirm this [41, 55, 56].”
BackgroundSelf-citationZekry, O., Ahmed, M. A., & Elwahid, H. A. E. A. (2013) · The Egyptian Rheumatologist · doi:10.1016/j.ejr.2012.12.002 · Cited by 14 · see citing works
Joint Hypermobility Classes in 9-Year-Old Children from the General Population and Anxiety Symptoms
Ezpeleta, L., Navarro, J. B., Osa, N. D. L., Penelo, E., & Bulbena, A. (2018) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0000000000000577 · Cited by 13 · see citing works
Prevalence of generalized joint hypermobility in children with anxiety disorders
Javadi Parvaneh, V., Modaress, S., Zahed, G., Rahmani, K., & Shiari, R. (2020) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-020-03377-0 · Cited by 9 · cited 1× · see citing works
“Furthermore, an increased incidenceof other psychiatric disorders, including panic disorders [58, 69] and anxiety disorders [67, 68, 70] were found to be associatedwithG-HSD/hEDS.”
Backgroundvan Meulenbroek, T., Huijnen, I. P. J., Wiertz, C. M. H., & Verbunt, J. A. (2017) · Journal of Orthopaedic & Sports Physical Therapy · doi:10.2519/jospt.2017.7282 · Cited by 8 · see citing works
Self-citationJoint hypermobility is a marker for anxiety in children
Bulbena-Cabré, A., Duñó, L., Almeda, S., Batlle, S., Camprodon-Rosanas, E., Martín-López, L. M., & Bulbena, A. (2019) · Revista de Psiquiatría y Salud Mental (English Edition) · doi:10.1016/j.rpsmen.2019.05.001 · Cited by 3 · see citing works
Flagged first, then by citations
4 of the 88 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
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- Remvig L, Engelbert RH, Berglund B, Bulbena A, Byers PH, Grahame R, et al. Need for a consensus on the methods by which to measure joint mobility and the definition of norms for hypermobility that reflect age, gender and ethnic-dependent variation: is revision of criteria for joint hypermobility syndrome and Ehlers-Danlos syndrome hypermobility type indicated? Rheumatology 2011;50:1169-71.
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Cited by
Sorted by citations
den Hollander, M., Smeets, R. J. E. M., van Meulenbroek, T., van Laake-Geelen, C. C. M., Baadjou, V. A., & Timmers, I. (2022) · Physical Therapy · doi:10.1093/ptj/pzab270 · Cited by 30 · see citing works
Bennett, S. E., Walsh, N., Moss, T., & Palmer, S. (2022) · Disability and Rehabilitation · doi:10.1080/09638288.2021.1933618 · Cited by 16 · see citing works
Warnink‐Kavelaars, J., de Koning, L. E., Rombaut, L., Alsem, M. W., Menke, L. A., Oosterlaan, J., Buizer, A. I., Engelbert, R., & on behalf of the Pediatric Heritable Connective Tissue Disorders Study Group (2021) · Genes · doi:10.3390/genes12060831 · Cited by 22 · see citing works
Self-citationBylund‐Grenklo, T., & Efverman, A. (2024) · Integrative Cancer Therapies · doi:10.1177/15347354241303454 · Cited by 12 · see citing works
Larivière, C., Rabhi, K., Preuss, R. A., Coutu, M., Roy, N., & Henry, S. M. (2022) · PLoS ONE · doi:10.1371/journal.pone.0265970 · Cited by 13 · see citing works
“Joint hypermobility syndrome, as diagnosed with the Beighton scale, is thought to be caused by a decrease in collagen content in tendons, ligaments, joint capsules, and skin, which in turn reduces their stiffness and thus may have a relationship with joint instability and pain [61].”
BackgroundPhysical activity and physical fitness in children with heritable connective tissue disorders
de Koning, L. E., Warnink‐Kavelaars, J., van Rossum, M. A. J., Limmen, S., der Looven, R. V., Mosquera, L. M., van der Hulst, A. E., Oosterlaan, J., Rombaut, L., Engelbert, R., et al. (2023) · Frontiers in Pediatrics · doi:10.3389/fped.2023.1057070 · Cited by 15 · see citing works
“In contrast, in line with more recent studies (52, 53), we did not find significant differences between children with and without GJH.”
ResultSelf-citationWarnink‐Kavelaars, J., de Koning, L. E., Rombaut, L., Menke, L. A., Alsem, M. W., van Oers, H. A., Buizer, A. I., Engelbert, R., Oosterlaan, J., & Pediatric Heritable Connective Tissue Disorder study group (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62750 · Cited by 14 · see citing works
Self-citationJeong, H., Engel, J. M., Wilwert, O., Muriello, M. J., Basel, D., & Slavens, B. A. (2023) · Physical & Occupational Therapy In Pediatrics · doi:10.1080/01942638.2022.2163601 · Cited by 10 · see citing works
“Our study participants showed moderate pain catastrophic thinking, whereas Van Meulenbroek et al. reported higher PCS-C scores in adolescents with hEDS/HSD (Van Meulenbroek et al., 2020) and chronic pain with hypermobility (Van Meulenbroek et al., 2017).”
BackgroundResultInfluentialÇalışkan, F., Seller, A., & Gerçek, M. (2024) · Journal of Perianesthesia Nursing · doi:10.1016/j.jopan.2024.07.015 · Cited by 8 · see citing works
de Vries, J., Verbunt, J., Stubbe, J., Visser, B., Ramaekers, S., Calders, P., & Engelbert, R. (2021) · Healthcare · doi:10.3390/healthcare9050525 · Cited by 8 · see citing works
“in participants with high trait anxiety [27], and a recent review on hypermobile adolescents and young adults proposed that vulnerability to anxiety might cause avoidance behavior as a coping strategy to avoid injury and complaints [9].”
BackgroundSelf-citationItuen, O. A., Akwaowo, C., Ferguson, G. D., Duysens, J., & Smits-Engelsman, B. C. M. (2025) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-024-08259-3 · Cited by 10 · see citing works
Higo, A., Palmer, S., Liaghat, B., Tallis, J. A., Silvester, L. J., & Pearce, G. (2024) · Archives of Rehabilitation Research and Clinical Translation · doi:10.1016/j.arrct.2024.100360 · Cited by 6 · see citing works
“59 This fear and risk of injury underscore the importance of designing future studies focused on re fi ning exercise parameters for people living with hEDS/HSD.”
BackgroundBénistan, K., Pontier, B., Leblond, C., Flageul, O., Guicher, G. L., Enjalbert, M., & Gillas, F. (2023) · Healthcare · doi:10.3390/healthcare11131862 · Cited by 6 · see citing works
Laekeman, M., Schäfer, A., Moog, M., & Kuss, K. (2021) · Children · doi:10.3390/children8050390 · Cited by 6 · see citing works
“, catastrophizing thoughts, pain-related anxiety) appear to have an impact on the development or maintenance of chronic musculoskeletal pain [55].”
BackgroundSokol, O. E., Biggs, E. E., Berger, A. S., Simons, L. E., & Bhandari, R. P. (2025) · Children · doi:10.3390/children12020170 · Cited by 6 · see citing works
“Among youth with chronic musculoskeletal pain, the prevalence of generalized joint hypermobility is 35–48% [8].”
Self-citationItuen, O. A., Duysens, J., Ferguson, G. D., & Smits-Engelsman, B. C. M. (2025) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-025-08684-y · Cited by 3 · see citing works
“Such data are crucial for understanding the mechanisms behind the observed changes in joint laxity and the risk of damage to mechanoreceptors often seen in recurrent sprains [26].”
van Die-de Vries, J., Verbunt, J., Ramaekers, S., Calders, P., & Engelbert, R. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19052662 · Cited by 3 · see citing works
Self-citationSensing hand position in Ehlers-Danlos syndrome
Clayton, H. A., Hart, B. M. ’., & Henriques, D. Y. P. (2021) · Somatosensory & Motor Research · doi:10.1080/08990220.2021.1973403 · Cited by 3 · see citing works
“[22] suggested that the proprioceptive differences commonly seen in adolescents with Hypermobile EDS could be due to physical deconditioning, because of kinesiophobia, since those with joint hypermobility are more prone”
BackgroundInfluentialMolecular Pathogenesis of Joint Hypermobility: The Role of Intergenic Interactions
Akhiiarova, K., Tyurin, A., & Khusainova, R. (2025) · Medical Science · doi:10.3390/medsci13040223 · Cited by 2 · see citing works
“The clinical presentation of JH varies from asymptomatic hypermobility to pronounced joint pain [3] and instability.”
Chew, M. T., İlhan, E., Nicholson, L. L., Kobayashi, S., Pacey, V., Hakim, A. J., & Chan, C. L. (2025) · European Journal of Pain · doi:10.1002/ejp.70030 · Cited by 2 · see citing works
“These challenges contribute to ongoing pain and disability (van Meulenbroek et al. 2021).”
Jeong, H., Tarima, S. S., Nguyen, A., Qashqai, A., Muriello, M. J., Basel, D., & Slavens, B. A. (2024) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2024.112151 · Cited by 2 · see citing works
Warnink-Kavelaars, J., de Koning, L. E., van der Hulst, A. E., Buizer, A., Poissonnier, N., Wijninga, L. E., Menke, L., Mosquera, L. M., Rombaut, L., & Engelbert, R. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05456-z · Cited by 2 · see citing works
Self-citationPemanfaatan Tanaman Herbal Dalam Pengobatan Nyeri Berdasarkan Kearifan Lokal Bali Usada Tiwang
Ekayanti, N. K. R. L. (2023) · Prosiding Workshop dan Seminar Nasional Farmasi · doi:10.24843/wsnf.2022.v01.i01.p31 · Cited by 2
Role of Anxiety in Individuals with Generalized Joint Hypermobility: A Systematic Review
van Die-de Vries, J. E., Rameckers, E., Calders, P., Engelbert, R. H., Ramaekers, S. P., Goossens, M. E., & Verbunt, J. A. (2025) · Archives of Rehabilitation Research and Clinical Translation · doi:10.1016/j.arrct.2025.100467 · Cited by 1 · see citing works
Self-citationWard, S. L., MacDermott, E. J., Simmonds, J. V., Deane, J. A., Mockler, D., & Dockrell, S. (2022) · Physiotherapy Practice and Research · doi:10.3233/ppr-220699 · Cited by 1 · see citing works
Chappell, A., Jepson, B., & Kilgour, G. M. (2026) · Child: Care, Health and Development · doi:10.1111/cch.70345
Calder, J. S., Louw, A., & Zimney, K. (2025) · Journal of Medical - Clinical Research & Reviews · doi:10.33425/2639-944x.1417
“More importantly, biomedical models often fuel powerful beliefs when it comes to tests and treatments [10,13].”
InfluentialOrenius, T., von Smitten-Stubb, K., Kautiainen, H., Montin, L., Bulbena, A., & Lindgren, K.-A. (2025) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2024-0055
Raisonnement clinique et triage autour de l’instabilité cervicale haute
Duhourcau, Y., & Lafitte-Houssat, B. (2023) · Kinésithérapie, la Revue · doi:10.1016/j.kine.2023.08.015
- Authors
- van Meulenbroek, T., Huijnen, I. P. J., Simons, L. E., Conijn, A. E. A., Engelbert, R. H. H., & Verbunt, J. A.
- Affiliations
- Medicine, Research School CAPHRI, Maastricht University , Maastricht , The Netherlands
- Maastricht University (NL)
- Stanford Medicine (US)
- Amsterdam University Medical Centers (NL)
- ORCID
- Venue
- Scandinavian Journal of Pain
- Publisher
- Walter de Gruyter GmbH
- Published
- 2020-08-31
- Volume
- 21
- Issue
- 1
- Pages
- 22-31
- ISSN
- 1877-8860 (ISSN-L)
- 1877-8879
- OpenAlex
- W3082414526
- Cited by
- 30
- References
- 88
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 6
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Scandinavian Journal of Pain (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Fonds Nuts Ohra, Stichting Vooruit and Adelante
- Topics
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pediatric Pain Management Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- chronic musculoskeletal pain, generalized joint hypermobility, hypermobile Ehlers-Danlos syndrome, pain-related disability, fear of pain, fear-avoidance model, adolescents, catastrophizing, generalized anxiety disorder, biopsychosocial model
- MeSH terms
- Adolescent, Child, Ehlers-Danlos Syndrome, Humans, Joint Instability, Quality of Life, Chronic Pain, Musculoskeletal Pain
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