{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:15Z","timestamp":1787029155502,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPESP","award":["17\/12943-8"],"award-info":[{"award-number":["17\/12943-8"]}]},{"name":"FAPESP","award":["R01 AT009491-01A1"],"award-info":[{"award-number":["R01 AT009491-01A1"]}]},{"name":"National Institutes of Health (NIH)","award":["17\/12943-8"],"award-info":[{"award-number":["17\/12943-8"]}]},{"name":"National Institutes of Health (NIH)","award":["R01 AT009491-01A1"],"award-info":[{"award-number":["R01 AT009491-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Background: Fibromyalgia syndrome (FMS), a chronic pain syndrome affecting 0.2\u20136.6% of the general population, is known for its challenging diagnosis and treatment. The known dysregulation in the Endogenous Pain Modulatory System (EPMS) characteristic of the pathology contributes to enhanced pain sensitivity. Fibromyalgia patients, who are often overmedicated, may experience, in addition to the drug-related known adverse effects, effects on fibromyalgia sensory-related outcomes. Therefore, the focus of this analysis is to explore the bidirectional drug\u2013sensory outcome interactions, indexed by the conditioned pain modulation (CPM), an important assessment element in regard to an EPMS\u2019s efficacy. Methods: Baseline data from a randomized, double-blind, single-center (Boston-based tertiary hospital) clinical trial (NCT03371225) were analyzed. Participants aged 18\u201365 with an FMS diagnosis and resistance to common analgesics were included. Demographic, clinical, and sensory variables, including CPM, temporal summation, and Pain-60 outcomes, were collected alongside a pain medication diary. Multivariable regression models adjusted for confounders were applied to explore associations between medication classes and quantitative sensory outcomes. Results: Out of 101 recruited FMS patients, we categorized the use of the following medications: antidepressants with 50% use (n = 50), muscle relaxants with 26% use (n = 26), and gabapentin with 25% use (n = 25). The results showed that antidepressant use correlated with worsened CPM, Odds Ratio = 0.39 (95% CI = 0.17\u20130.91), while muscle relaxants were linked to increased TSPS, \u03b2 coefficient = 0.72 (95% CI = 0.0021\u20131.4431). On the other hand, gabapentin use was associated with elevated Pain-60, OR = 2.68 (95% CI = 0.98\u20137.31). Interestingly, the use of low doses of opioids was not associated with altered sensory measures. Conclusion: This cross-sectional analysis suggests that common pain medications may affect quantitative sensory outcomes in FMS patients. We provided important insights into bidirectional drug\u2013sensory outcome interactions and their influence on pain medicine.<\/jats:p>","DOI":"10.3390\/neurosci6010015","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T09:29:26Z","timestamp":1739179766000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Association of Pain Medication Usage and Quantitative Sensory Testing Outcomes in Fibromyalgia Patients: A Secondary Data Analysis"],"prefix":"10.3390","volume":"6","author":[{"given":"Luana Gola","family":"Alves","sequence":"first","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Pacheco-Barrios","sequence":"additional","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA 02138, USA"},{"name":"Vicerrectorado de Investigaci\u00f3n, Unidad de Investigaci\u00f3n para la Generaci\u00f3n y S\u00edntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima 15024, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1449-6539","authenticated-orcid":false,"given":"Guilherme J. 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Ed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.jad.2020.01.129","article-title":"Depression and trait-anxiety mediate the influence of clinical pain on health-related quality of life in fibromyalgia","volume":"265","author":"Montoro","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrrheum.2015.56","article-title":"The role of sleep in pain and fibromyalgia","volume":"11","author":"Choy","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s11926-001-0008-3","article-title":"The role of gender in fibromyalgia syndrome","volume":"3","author":"Yunus","year":"2001","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1469-7580.2007.00759.x","article-title":"From neuroanatomy to gene therapy: Searching for new ways to manipulate the supraspinal endogenous pain modulatory system","volume":"211","author":"Tavares","year":"2007","journal-title":"J. Anat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0028-3908(98)00141-5","article-title":"Transport of brain-derived neurotrophic factor across the blood-brain barrier","volume":"37","author":"Pan","year":"1998","journal-title":"Neuropharmacology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/0169-328X(95)00250-V","article-title":"Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF","volume":"36","author":"Poduslo","year":"1996","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neucli.2020.11.002","article-title":"Conditioned pain modulation\u2014A comprehensive review","volume":"51","author":"Ramaswamy","year":"2021","journal-title":"Neurophysiol. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jpsychores.2010.09.012","article-title":"Autonomic cardiovascular control and responses to experimental pain stimulation in fibromyalgia syndrome","volume":"70","author":"Garrido","year":"2011","journal-title":"J. Psychosom. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S1521-6942(03)00036-6","article-title":"Evoked pain measures in fibromyalgia","volume":"17","author":"Gracely","year":"2003","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e032710","DOI":"10.1136\/bmjopen-2019-032710","article-title":"Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: A randomised, double-blind, factorial clinical trial protocol","volume":"9","author":"Duarte","year":"2019","journal-title":"BMJ Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1097\/j.pain.0000000000000689","article-title":"Reliability of conditioned pain modulation: A systematic review","volume":"157","author":"Kennedy","year":"2016","journal-title":"Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/acr.20140","article-title":"The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity","volume":"62","author":"Wolfe","year":"2010","journal-title":"Arthritis Care Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1002\/acr.20531","article-title":"Measures of fibromyalgia: Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Multidimensional Fatigue Inventory (MFI-20), Medical Outcomes Study (MOS) Sleep Scale, and Multiple Ability Self-Report Questionnaire (MASQ)","volume":"63","author":"Williams","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"An inventory for measuring depression","volume":"4","author":"Beck","year":"1961","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1477-7525-1-60","article-title":"The Quality of Life Scale (QOLS): Reliability, validity, and utilization","volume":"1","author":"Burckhardt","year":"2003","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jphys.2015.07.001","article-title":"The Brief Pain Inventory (BPI)","volume":"62","author":"Poquet","year":"2016","journal-title":"J. Physiother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1007\/s11136-018-1842-3","article-title":"PROMIS(\u00ae)-29 v2.0 profile physical and mental health summary scores","volume":"27","author":"Hays","year":"2018","journal-title":"Qual. Life Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1477-7525-8-57","article-title":"Psychometric evaluation of a visual analog scale for the assessment of anxiety","volume":"8","author":"Williams","year":"2010","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/01.mlr.0000258615.42478.55","article-title":"The Patient-Reported Outcomes Measurement Information System (PROMIS): Progress of an NIH Roadmap cooperative group during its first two years","volume":"45","author":"Cella","year":"2007","journal-title":"Med. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/1759720X11416863","article-title":"Simplifying Fibromyalgia Assessment: The VASFIQ Brief Symptom Scale","volume":"3","author":"Boomershine","year":"2011","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.pain.2007.06.029","article-title":"Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: Do conditioning stimulus painfulness, gender and personality variables matter?","volume":"136","author":"Granot","year":"2008","journal-title":"Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ejpain.2010.10.001","article-title":"A psychophysical study of endogenous analgesia: The role of the conditioning pain in the induction and magnitude of conditioned pain modulation","volume":"15","author":"Nir","year":"2011","journal-title":"Eur. J. Pain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1097\/ACO.0b013e32833c348b","article-title":"Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): Its relevance for acute and chronic pain states","volume":"23","author":"Yarnitsky","year":"2010","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Staud, R., Weyl, E.E., Riley, J.L., and Fillingim, R.B. (2014). Slow temporal summation of pain for assessment of central pain sensitivity and clinical pain of fibromyalgia patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089086"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s10072-021-05806-x","article-title":"The puzzle of fibromyalgia between central sensitization syndrome and small fiber neuropathy: A narrative review on neurophysiological and morphological evidence","volume":"43","author":"Vecchio","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104691","DOI":"10.1016\/j.jpain.2024.104691","article-title":"High Body Mass Index Disrupts the Homeostatic Effects of Pain Inhibitory Control in the Symptomatology of Patients with Fibromyalgia","volume":"25","author":"Lacerda","year":"2024","journal-title":"J. Pain"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bennett, R.M., Jones, J., Turk, D.C., Russell, I.J., and Matallana, L. (2007). An internet survey of 2596 people with fibromyalgia. BMC Musculoskelet. Disord., 8.","DOI":"10.1186\/1471-2474-8-27"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1007\/s00482-011-1079-3","article-title":"Treatment and healthcare costs of fibromyalgia syndrome in Germany: Analysis of the data of the Barmer health insurance (BEK) from 2008\u20132009","volume":"25","author":"Marschall","year":"2011","journal-title":"Der Schmerz"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1136\/ard.2007.071522","article-title":"EULAR evidence-based recommendations for the management of fibromyalgia syndrome","volume":"67","author":"Carville","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","first-page":"383","article-title":"Fibromyalgia syndrome: Classification, diagnosis, and treatment","volume":"106","author":"Eich","year":"2009","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/138161206775193253","article-title":"Fibromyalgia syndrome: Which antidepressant drug should we choose","volume":"12","author":"Littlejohn","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0072-9752(06)80017-5","article-title":"Chapter 13 Descending inhibitory systems","volume":"81","author":"Pertovaara","year":"2006","journal-title":"Handb. Clin. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Obata, H. (2017). Analgesic Mechanisms of Antidepressants for Neuropathic Pain. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112483"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.17085\/apm.23055","article-title":"Does adding muscle relaxant make post-operative pain better? A narrative review of the literature from US and European studies","volume":"18","author":"Verdiner","year":"2023","journal-title":"Anesth. Pain Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF00505069","article-title":"Studies on the mechanism of action of dantrolene sodium. A skeletal muscle relaxant","volume":"275","author":"Ellis","year":"1972","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40122-021-00235-2","article-title":"Management of Musculoskeletal Pain: An Update with Emphasis on Chronic Musculoskeletal Pain","volume":"10","author":"Nalamasu","year":"2021","journal-title":"Pain Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1093\/pm\/pnab088","article-title":"Utilization Patterns of Skeletal Muscle Relaxants Among Commercially Insured Adults in the United States from 2006 to 2018","volume":"22","author":"Li","year":"2021","journal-title":"Pain Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"478","DOI":"10.7326\/0003-4819-147-7-200710020-00006","article-title":"Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society","volume":"147","author":"Chou","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"m1315","DOI":"10.1136\/bmj.m1315","article-title":"Pregabalin and gabapentin for pain","volume":"369","author":"Mathieson","year":"2020","journal-title":"BMJ"},{"key":"ref_41","first-page":"Cd011790","article-title":"Pregabalin for pain in fibromyalgia in adults","volume":"9","author":"Derry","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.pain.2009.05.014","article-title":"Treatment of fibromyalgia syndrome with gabapentin and pregabalin\u2014A meta-analysis of randomized controlled trials","volume":"145","author":"Bernardy","year":"2009","journal-title":"Pain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/03007995.2017.1391756","article-title":"Is there a role for combined use of gabapentin and pregabalin in pain control? Too good to be true?","volume":"34","author":"Senderovich","year":"2018","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/00000542-200207000-00015","article-title":"Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization","volume":"97","author":"Dirks","year":"2002","journal-title":"Anesthesiology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zortea, M., Ramalho, L., Alves, R.L., Alves, C., Braulio, G., Torres, I., Fregni, F., and Caumo, W. (2019). Transcranial Direct Current Stimulation to Improve the Dysfunction of Descending Pain Modulatory System Related to Opioids in Chronic Non-cancer Pain: An Integrative Review of Neurobiology and Meta-Analysis. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01218"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.1523\/JNEUROSCI.21-11-04074.2001","article-title":"Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: A sensitization process","volume":"21","author":"Laulin","year":"2001","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.bpa.2006.12.004","article-title":"The impact of opioid-induced hyperalgesia for postoperative pain","volume":"21","author":"Koppert","year":"2007","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/ALN.0000000000000963","article-title":"Differential Opioid Tolerance and Opioid-induced Hyperalgesia: A Clinical Reality","volume":"124","author":"Hayhurst","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s10067-015-3144-2","article-title":"A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria","volume":"35","author":"Papadopoulou","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1136\/annrheumdis-2016-209724","article-title":"EULAR revised recommendations for the management of fibromyalgia","volume":"76","author":"Macfarlane","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_51","first-page":"F1000","article-title":"Physical therapy modalities for treating fibromyalgia","volume":"8","author":"DeSantana","year":"2019","journal-title":"F1000Research"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1001\/jama.2008.944","article-title":"Treatment of fibromyalgia syndrome with antidepressants: A meta-analysis","volume":"301","author":"Bernardy","year":"2009","journal-title":"JAMA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/14737175.2020.1738927","article-title":"Noninvasive brain stimulation combined with exercise in chronic pain: A systematic review and meta-analysis","volume":"20","author":"Fregni","year":"2020","journal-title":"Expert Rev. Neurother."}],"container-title":["NeuroSci"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4087\/6\/1\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:30:31Z","timestamp":1760027431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4087\/6\/1\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["neurosci6010015"],"URL":"https:\/\/doi.org\/10.3390\/neurosci6010015","relation":{},"ISSN":["2673-4087"],"issn-type":[{"value":"2673-4087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]}}}