{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:04:08Z","timestamp":1760234648993,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>Identification of subgroups of patients with chronic pain provides meaningful insights into the characteristics of a specific population, helping to identify individuals at risk of chronification and to determine appropriate therapeutic strategies. This paper proposes the use of spectral clustering (SC) to distinguish subgroups (clusters) of individuals with carpal tunnel syndrome (CTS), making use of the obtained patient profiling to argue about potential management implications. SC is a powerful algorithm that builds a similarity graph among the data points (the patients), and tries to find the subsets of points that are strongly connected among themselves, but weakly connected to others. It was chosen due to its advantages with respect to other simpler clustering techniques, such as k-means, and the fact that it has been successfully applied to similar problems. Clinical (age, duration of symptoms, pain intensity, function, and symptom severity), psycho-physical (pressure pain thresholds\u2014PPTs\u2014over the three main nerve trunks of the upper extremity, cervical spine, carpal tunnel, and tibialis anterior), psychological (depressive levels), and motor (pinch tip grip force) variables were collected in 208 women with clinical\/electromyographic diagnosis of CTS, whose symptoms usually started unilaterally but eventually evolved into bilateral symmetry. SC was used to identify clusters of patients without any previous assumptions, yielding three clusters. Patients in cluster 1 exhibited worse clinical features, higher widespread pressure pain hyperalgesia, higher depressive levels, and lower pinch tip grip force than the other two. Patients in cluster 2 showed higher generalized thermal pain hyperalgesia than the other two. Cluster 0 showed less hypersensitivity to pressure and thermal pain, less severe clinical features, and more normal motor output (tip grip force). The presence of subgroups of individuals with different altered nociceptive processing (one group being more sensitive to pressure pain and another group more sensitive to thermal pain) could lead to different therapeutic programs.<\/jats:p>","DOI":"10.3390\/sym13061042","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T14:16:04Z","timestamp":1623248164000},"page":"1042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spectral Clustering Reveals Different Profiles of Central Sensitization in Women with Carpal Tunnel Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-1029","authenticated-orcid":false,"given":"Oscar J.","family":"Pellicer-Valero","sequence":"first","affiliation":[{"name":"Intelligent Data Analysis Laboratory, Department of Electronic Engineering, ETSE (Engineering School), Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-0285","authenticated-orcid":false,"given":"Jos\u00e9 D.","family":"Mart\u00edn-Guerrero","sequence":"additional","affiliation":[{"name":"Intelligent Data Analysis Laboratory, Department of Electronic Engineering, ETSE (Engineering School), Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-9690","authenticated-orcid":false,"given":"C\u00e9sar","family":"Fern\u00e1ndez-de-las-Pe\u00f1as","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Madrid, Spain"}]},{"given":"Ana I.","family":"De-la-Llave-Rinc\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Madrid, Spain"}]},{"given":"Jorge","family":"Rodr\u00edguez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-2909","authenticated-orcid":false,"given":"Esperanza","family":"Navarro-Pardo","sequence":"additional","affiliation":[{"name":"Departamento de Psicolog\u00eda Evolutiva y de la Educaci\u00f3n, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}]},{"given":"Margarita I.","family":"Cigar\u00e1n-M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Department of Psychology, Universidad Rey Juan Carlos, 28922 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1016\/j.apmr.2014.08.004","article-title":"Effects of Varying Case Definition on Carpal Tunnel Syndrome Prevalence Estimates in a Pooled Cohort","volume":"95","author":"Thiese","year":"2014","journal-title":"Arch. Phys. Med. Rehabilit."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/mus.26145","article-title":"Carpal tunnel release: Lifetime prevalence, annual incidence, and risk factors","volume":"58","author":"Pourmemari","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e174947","DOI":"10.1001\/jamasurg.2017.4947","article-title":"Prevalence of Work-Related Musculoskeletal Disorders Among Surgeons and Interventionalists: A Systematic Review and Meta-analysis","volume":"153","author":"Epstein","year":"2018","journal-title":"JAMA Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"495","DOI":"10.5271\/sjweh.3351","article-title":"Prevalence and incidence of carpal tunnel syndrome in US working populations: Pooled analysis of six prospective studies","volume":"39","author":"Dale","year":"2013","journal-title":"Scand. J. Work Environ. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1002\/ajim.22540","article-title":"The long-term burden of work-related carpal tunnel syndrome relative to upper-extremity fractures and dermatitis in Washington State","volume":"58","author":"Foley","year":"2015","journal-title":"Am. J. Ind. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Genova, A., Dix, O., Saefan, A., Thakur, M., and Hassan, A. (2020). Carpal Tunnel Syndrome: A Review of Literature. Cureus, 12.","DOI":"10.7759\/cureus.7333"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2217\/pmt-2017-0063","article-title":"Carpal tunnel syndrome: Just a peripheral neuropathy?","volume":"8","year":"2018","journal-title":"Pain Manag."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1093\/brain\/awp050","article-title":"Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: Evidence of central processing in unilateral neuropathy","volume":"132","author":"Cuadrado","year":"2009","journal-title":"Brain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00221-009-1941-z","article-title":"Bilateral hand\/wrist head and cold hyperalgesia, but not hypoesthesia, in unilateral carpal tunnel syndrome","volume":"198","author":"Padua","year":"2009","journal-title":"Exp Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.pain.2009.10.025","article-title":"Central sensitization in carpal tunnel syndrome with extraterritorial spread of sensory symptoms","volume":"148","author":"Zanette","year":"2010","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00221-008-1666-4","article-title":"Bilateral deficits in fine motor control and pinch grip force in patients with unilateral carpal tunnel syndrome","volume":"194","author":"Cleland","year":"2009","journal-title":"Exp. Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1093\/pm\/pnw054","article-title":"Identification of Subgroups of Women with Carpal Tunnel Syndrome with Central Sensitization","volume":"17","author":"Quesada","year":"2016","journal-title":"Pain Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10618-012-0291-9","article-title":"On constrained spectral clustering and its applications","volume":"28","author":"Wang","year":"2012","journal-title":"Data Min. Knowl. Discov."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pellicer-Valero, O.J., Mart\u00edn-Guerrero, J.D., Cigar\u00e1n-M\u00e9ndez, M.I., \u00c9cija-Gallardo, C., Fern\u00e1ndez-De-Las-Pe\u00f1as, C., and Navarro-Pardo, E. (2020). Mathematical Modeling for Neuropathic Pain: Bayesian Linear Regression and Self-Organizing Maps Applied to Carpal Tunnel Syndrome. Symmetry, 12.","DOI":"10.3390\/sym12101581"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"American Association of Electro-diagnostic Medicine, American Academy of Neurology, and American Academy of Physical Medicine and Rehabilitation (2002). Practice parameter: Electro-diagnostic studies in carpal tunnel syndrome. Neurology, 58, 1589\u20131592.","DOI":"10.1212\/WNL.58.11.1589"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0304-3959(99)00101-3","article-title":"Comparative reliability and validity of chronic pain intensity measures","volume":"83","author":"Jensen","year":"1999","journal-title":"Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1053\/jhsu.2002.30059","article-title":"Evaluation of the Spanish version of the DASH and carpal tunnel syn-drome health-related quality of life instruments: Cross cultural adaptation process and reliability","volume":"27","author":"Rosales","year":"2002","journal-title":"J. Hand Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.2106\/00004623-199311000-00002","article-title":"A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome","volume":"75","author":"Levine","year":"1993","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1471-2474-7-78","article-title":"A systematic review of the psychometric properties of the Boston Carpal Tunnel Questionnaire","volume":"7","author":"Song","year":"2006","journal-title":"BMC Musculoskelet. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Beck, A.T., Steer, R.A., and Brown, G.K. (1996). Beck Depression Inventory, The Psychological Corporation. [2nd ed.].","DOI":"10.1037\/t00742-000"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.jpain.2007.04.003","article-title":"Test-Retest Reliability of Pressure Pain Threshold Measurements of the Upper Limb and Torso in Young Healthy Women","volume":"8","author":"Jones","year":"2007","journal-title":"J. Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/mus.22121","article-title":"Reliability of thermal quantitative sensory testing of the hand in a cohort of young, healthy adults","volume":"44","author":"Moloney","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1093\/ptj\/83.9.806","article-title":"Measurement Error in Grip and Pinch Force Measurements in Patients with Hand Injuries","volume":"83","author":"Schreuders","year":"2003","journal-title":"Phys. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s11222-007-9033-z","article-title":"A tutorial on spectral clustering","volume":"17","year":"2007","journal-title":"Stat. Comput."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1109\/34.868688","article-title":"Normalized cuts and image segmentation","volume":"22","author":"Shi","year":"2000","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pellicer-Valero, O.J., Fern\u00e1ndez-De-Las-Pe\u00f1as, C., Mart\u00edn-Guerrero, J.D., Navarro-Pardo, E., Cigar\u00e1n-M\u00e9ndez, M.I., and Florencio, L.L. (2020). Patient Profiling Based on Spectral Clustering for an Enhanced Classification of Patients with Tension-Type Headache. Appl. Sci., 10.","DOI":"10.3390\/app10249109"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_28","unstructured":"Skipper, S., and Perktold, J. (July, January 28). Statsmodels: Econometric and statistical modeling with phyton. Proceedings of the 9th Python in Science Conference, Austin, TX, USA."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1097\/AJP.0b013e31821c29d3","article-title":"Increased pain sensitivity is not associated with electrodiagnostic findings in women with carpal tunnel syn-drome","volume":"27","author":"Pareja","year":"2011","journal-title":"Clin. J. Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0303-2647(97)01685-7","article-title":"Cold and post-traumatic pain: Modeling of the peripheral nerve message","volume":"43","author":"Hurpeau","year":"1997","journal-title":"Biosystems"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: Implications for the diagnosis and treatment of pain","volume":"152","author":"Woolf","year":"2011","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.arcmed.2012.07.004","article-title":"Evaluation of Upper Extremity Nerve Conduction Velocities and the Relationship Between Fibromyalgia and Carpal Tunnel Syndrome","volume":"43","author":"Nacir","year":"2012","journal-title":"Arch. Med. Res."},{"key":"ref_33","first-page":"249","article-title":"Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review","volume":"17","author":"Smart","year":"2016","journal-title":"Pain Pract."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Roh, Y.H., Kim, S., Gong, H.S., and Baek, G.H. (2018). Influence of centrally mediated symptoms on functional outcomes after carpal tunnel release. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29522-3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/papr.12788","article-title":"Influence of Clinical, Psychological, and Psychophysical Variables on Long-term Treatment Outcomes in Carpal Tunnel Syndrome: Evidence From a Randomized Clinical Trial","volume":"19","author":"Cescon","year":"2019","journal-title":"Pain Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1007\/s00415-008-0895-6","article-title":"Pain and motor function in carpal tunnel syndrome: A clinical, neuro-physiological and psychophysical study","volume":"255","author":"Tamburin","year":"2008","journal-title":"J. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3233\/NRE-182589","article-title":"Upper extremity disability is associated with pain intensity and grip strength in women with bilateral idiopathic carpal tunnel syndrome","volume":"44","author":"Yoshida","year":"2019","journal-title":"NeuroRehabilitation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.jpain.2015.07.012","article-title":"Manual Physical Therapy Versus Surgery for Carpal Tunnel Syndrome: A Randomized Parallel-Group Trial","volume":"16","author":"Pareja","year":"2015","journal-title":"J. Pain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1111\/pme.12857","article-title":"Direct and Indirect Effects of Function in Associated Variables Such as Depression and Severity on Pain Intensity in Women with Carpal Tunnel Syndrome","volume":"16","year":"2015","journal-title":"Pain Med."}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/13\/6\/1042\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:12:33Z","timestamp":1760163153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/13\/6\/1042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,9]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["sym13061042"],"URL":"https:\/\/doi.org\/10.3390\/sym13061042","relation":{},"ISSN":["2073-8994"],"issn-type":[{"type":"electronic","value":"2073-8994"}],"subject":[],"published":{"date-parts":[[2021,6,9]]}}}