{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:42:27Z","timestamp":1783690947935,"version":"3.55.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008211","name":"Association France Parkinson","doi-asserted-by":"publisher","award":["No Number"],"award-info":[{"award-number":["No Number"]}],"id":[{"id":"10.13039\/501100008211","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Effectiveness of Foot Reflexology (FR) on the pain intensity in Parkinson\u2019s disease (PD) compared with Sham Massage (SM).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Design<\/jats:title>\n<jats:p>Monocentric, longitudinal, prospective, double-blind, randomized controlled trial. Randomization with a random number generator in the R software. Fixed-sized block randomization of 3 implemented into Clinsight.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Participants<\/jats:title>\n<jats:p>Idiopathic PD patients with chronic pain (Visual Analogue Scale (VAS)\u22654) were recruited from the Toulouse University Hospital between the 14th of April 2021 and the 25<jats:sup>th<\/jats:sup> of May 2025.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Intervention<\/jats:title>\n<jats:p>Four one-hour long FR or SM sessions three weeks apart with the same specialized FR researcher.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Main outcome measure<\/jats:title>\n<jats:p>Pain intensity change measured by the mean VAS before and after full completed interventions. The difference was compared between group using a Wilcoxon Mann Witney test. Exploratory outcome: brain functional connectivity<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Results<\/jats:title>\n<jats:p>30 PD patients were randomized and analyzed. Interventions were delivered as planned for all patients. Clinical variables did not significantly differed between FR and SM groups. Mean VAS decreased by \u221212.3 mm\u2009\u00b1\u200915.2 in FR group (n\u2009=\u200915) and \u221217.9 mm\u2009\u00b1\u200929.4 in SM group (n\u2009=\u200915). Analyses did not reveal any significant difference between the FR and SM groups (<jats:italic>p-value\u2009=\u20090.88<\/jats:italic>). There are different patterns in connectivity changes in the medial pain system between responders (at least 30% pain reduction) and non-responders to both therapies. There were no adverse events.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec007\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>FR is not more effective than SM in relieving chronic pain in PD. The differences in connectivity patterns within the medial pain pathway may underlie the response to tactile stimulation (FR and SM).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec008\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>ClinicalTrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04705207\" xlink:type=\"simple\">NCT04705207<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0327865","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T17:41:56Z","timestamp":1753724516000},"page":"e0327865","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of foot reflexology on chronic pain in Parkinson\u2019s disease: A randomized controlled trial"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4826-2731","authenticated-orcid":true,"given":"Karel","family":"Joineau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Harroch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3532-6743","authenticated-orcid":true,"given":"Mathilde","family":"Boussac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Fabbri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-4500","authenticated-orcid":true,"given":"Fabienne","family":"Ory-Magne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Rousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7200-0139","authenticated-orcid":true,"given":"Patrice","family":"Peran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Brefel-Courbon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-2989","authenticated-orcid":true,"given":"Emeline","family":"Descamps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"pone.0327865.ref001","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.pain.2008.12.004","article-title":"Pain in Parkinson\u2019s disease: Prevalence and characteristics","volume":"141","author":"AG Beiske","year":"2009","journal-title":"Pain"},{"issue":"4","key":"pone.0327865.ref002","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00702-012-0915-7","article-title":"The epidemiology of pain in Parkinson\u2019s disease","volume":"120","author":"G Defazio","year":"2013","journal-title":"J Neural Transm (Vienna)"},{"key":"pone.0327865.ref003","author":"L Negre-Pages","year":"2008"},{"key":"pone.0327865.ref004","article-title":"Management of Pain in Parkinson\u2019s Disease","volume":"10","author":"C Buhmann","year":"2020","journal-title":"J Parkinsons Dis"},{"issue":"3","key":"pone.0327865.ref005","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3390\/neurolint12030014","article-title":"Chronic Pain Treatment Strategies in Parkinson\u2019s Disease","volume":"12","author":"A Edinoff","year":"2020","journal-title":"Neurol Int"},{"issue":"1","key":"pone.0327865.ref006","first-page":"9","article-title":"Foot reflexology: recent research trends and prospects","volume":"11","author":"DC Cai","year":"2023","journal-title":"Healthcare"},{"issue":"6","key":"pone.0327865.ref007","doi-asserted-by":"crossref","first-page":"821","DOI":"10.4040\/jkan.2011.41.6.821","article-title":"Effects of foot reflexology on fatigue, sleep and pain: a systematic review and meta-analysis","volume":"41","author":"J Lee","year":"2011","journal-title":"J Korean Acad Nurs"},{"key":"pone.0327865.ref008","doi-asserted-by":"crossref","first-page":"102416","DOI":"10.1016\/j.eujim.2024.102416","article-title":"Reflexology specific guidance for using the template for the intervention description and replication (TIDieR): A delphi study","volume":"72","author":"J James","year":"2024","journal-title":"Eur J Integr Med"},{"issue":"12","key":"pone.0327865.ref009","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/mds.20629","article-title":"Effect of levodopa on pain threshold in Parkinson\u2019s disease: a clinical and positron emission tomography study","volume":"20","author":"C Brefel-Courbon","year":"2005","journal-title":"Mov Disord"},{"issue":"12","key":"pone.0327865.ref010","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1212\/01.WNL.0000130455.38550.9D","article-title":"Quantitative measurement of pain sensation in patients with Parkinson disease","volume":"62","author":"R Djaldetti","year":"2004","journal-title":"Neurology"},{"issue":"4","key":"pone.0327865.ref011","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00415-010-5812-0","article-title":"Spontaneous pain, pain threshold, and pain tolerance in Parkinson\u2019s disease","volume":"258","author":"S Zambito Marsala","year":"2011","journal-title":"J Neurol"},{"key":"pone.0327865.ref012","first-page":"467","article-title":"Alteration of Basal Ganglia and Right Frontoparietal Network in Early Drug-Na\u00efve Parkinson\u2019s Disease during Heat Pain Stimuli and Resting State","volume":"9","author":"Y Tan","year":"2015","journal-title":"Front Hum Neurosci"},{"issue":"12","key":"pone.0327865.ref013","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/mds.26826","article-title":"Anatomical and functional correlates of persistent pain in Parkinson\u2019s disease","volume":"31","author":"A Polli","year":"2016","journal-title":"Mov Disord"},{"issue":"1","key":"pone.0327865.ref014","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3390\/brainsci12010084","article-title":"Pain-Related Abnormal Neuronal Synchronization of the Nucleus Accumbens in Parkinson\u2019s Disease","volume":"12","author":"K Kinugawa","year":"2022","journal-title":"Brain Sci"},{"key":"pone.0327865.ref015","doi-asserted-by":"crossref","unstructured":"Joineau K, Boussac M, Peran P, Devos D, Houeto JL, Drapier S, et al. Parkinsonian central pain is linked to the connectivity of the nucleus accumbens and the anterior insula. Neuroimage Rep. 1 mars 2024;4(1):100197.","DOI":"10.1016\/j.ynirp.2024.100197"},{"issue":"1","key":"pone.0327865.ref016","doi-asserted-by":"crossref","first-page":"17139","DOI":"10.1038\/s41598-023-44325-x","article-title":"Changes of cerebral functional connectivity induced by foot reflexology in a RCT","volume":"13","author":"E Descamps","year":"2023","journal-title":"Sci Rep"},{"issue":"11","key":"pone.0327865.ref017","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1136\/jnnp.39.11.1071","article-title":"Method for quantitative estimation of thermal thresholds in patients","volume":"39","author":"H Fruhstorfer","year":"1976","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"3","key":"pone.0327865.ref018","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1089\/brain.2012.0073","article-title":"Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks","volume":"2","author":"S Whitfield-Gabrieli","year":"2012","journal-title":"Brain Connect"},{"key":"pone.0327865.ref019","doi-asserted-by":"crossref","first-page":"113","DOI":"10.56441\/hilbertpress.2207.6598","volume-title":"Handbook of functional connectivity Magnetic Resonance Imaging methods in CONN","author":"A Nieto-Castanon","year":"2020"},{"issue":"1","key":"pone.0327865.ref020","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.neuroimage.2007.04.042","article-title":"A component based noise correction method (CompCor) for BOLD and perfusion based fMRI","volume":"37","author":"Y Behzadi","year":"2007","journal-title":"Neuroimage"},{"issue":"47","key":"pone.0327865.ref021","doi-asserted-by":"crossref","first-page":"12165","DOI":"10.1523\/JNEUROSCI.3576-06.2006","article-title":"Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain","volume":"26","author":"MN Baliki","year":"2006","journal-title":"J Neurosci"},{"issue":"8","key":"pone.0327865.ref022","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/nn.3153","article-title":"Corticostriatal functional connectivity predicts transition to chronic back pain","volume":"15","author":"MN Baliki","year":"2012","journal-title":"Nat Neurosci"},{"issue":"10","key":"pone.0327865.ref023","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1089\/brain.2016.0436","article-title":"Human Posterior Insula Functional Connectivity Differs Between Electrical Pain and the Resting State","volume":"6","author":"KM Vogt","year":"2016","journal-title":"Brain Connect"},{"issue":"6240","key":"pone.0327865.ref024","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1126\/science.1255905","article-title":"BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks","volume":"348","author":"J Richiardi","year":"2015","journal-title":"Science"},{"issue":"1","key":"pone.0327865.ref025","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/cercor\/bhr099","article-title":"Decoding subject-driven cognitive states with whole-brain connectivity patterns","volume":"22","author":"WR Shirer","year":"2012","journal-title":"Cereb Cortex"},{"issue":"11","key":"pone.0327865.ref026","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1172\/JCI43498","article-title":"Pain imaging in health and disease--how far have we come?","volume":"120","author":"P Schweinhardt","year":"2010","journal-title":"J Clin Invest"},{"issue":"4","key":"pone.0327865.ref027","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1016\/j.neuroimage.2007.11.001","article-title":"A method for functional network connectivity among spatially independent resting-state components in schizophrenia","volume":"39","author":"MJ Jafri","year":"2008","journal-title":"Neuroimage"},{"key":"pone.0327865.ref028","article-title":"Foot reflexology in painful conditions: systematic review","author":"D Artioli","year":"2021","journal-title":"Braz J Pain"},{"issue":"1","key":"pone.0327865.ref029","doi-asserted-by":"crossref","first-page":"8","DOI":"10.53388\/TMRIN2020111701","article-title":"Effect of foot reflexology on pain and physiological indicators in postoperative patients: A systematic review and meta-analysis","volume":"5","author":"L Tian","year":"2021","journal-title":"Nurs Commun"},{"issue":"27","key":"pone.0327865.ref030","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000033939","article-title":"Massage therapy can effectively relieve cancer pain: A meta-analysis","volume":"102","author":"Y Zhang","year":"2023","journal-title":"Medicine (Baltimore)"},{"key":"pone.0327865.ref031","article-title":"The Benefits of Integrative Medicine in the Management of Chronic Pain: A Review","author":"H Trivedi","year":"2022","journal-title":"Cureus"},{"issue":"8","key":"pone.0327865.ref032","article-title":"Effectiveness of Manual Therapy and Acupuncture in Tension-Type Headache: A Systematic Review","volume":"13","author":"A Turkistani","year":"2021","journal-title":"Cureus"},{"key":"pone.0327865.ref033","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.ctcp.2022.101619","article-title":"Effect of manual soft tissue therapy on the pain in patients with chronic neck pain: A systematic review and meta-analysis","volume":"49","author":"S-Q Wang","year":"2022","journal-title":"Complement Ther Clin Pract"},{"key":"pone.0327865.ref034","doi-asserted-by":"crossref","first-page":"102340","DOI":"10.1016\/j.ctim.2020.102340","article-title":"Massage therapy as a complementary treatment for Parkinson\u2019s disease: A Systematic Literature Review","volume":"49","author":"E Angelopoulou","year":"2020","journal-title":"Complement Ther Med"},{"key":"pone.0327865.ref035","article-title":"The effectiveness and safety of non-pharmacological intervention for pain management in Parkinson\u2019s disease: A systematic review","author":"M Huissoud","year":"2023","journal-title":"Rev Neurol (Paris)"},{"issue":"2","key":"pone.0327865.ref036","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/ane.13435","article-title":"Non-pharmacological therapies for pain management in Parkinson\u2019s disease: A systematic review","volume":"144","author":"AR Qureshi","year":"2021","journal-title":"Acta Neurol Scand"},{"issue":"6","key":"pone.0327865.ref037","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.pmn.2018.07.007","article-title":"Relations among Pain, Pain Beliefs, and Psychological Well-Being in Patients with Chronic Pain","volume":"19","author":"S Yildizeli Topcu","year":"2018","journal-title":"Pain Manag Nurs"},{"key":"pone.0327865.ref038","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev-pharmtox-010818-021542","article-title":"The Placebo Effect in Pain Therapies","volume":"59","author":"L Colloca","year":"2019","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"1","key":"pone.0327865.ref039","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ijsu.2006.01.005","article-title":"The evolution of the doctor-patient relationship","volume":"5","author":"R Kaba","year":"2007","journal-title":"Int J Surg"},{"issue":"2","key":"pone.0327865.ref040","first-page":"100","article-title":"Placebo and nocebo effect: a mini-review","volume":"26","author":"I Po\u017egain","year":"2014","journal-title":"Psychiatr Danub"},{"key":"pone.0327865.ref041","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1472-6882-13-114","article-title":"Activity in the primary somatosensory cortex induced by reflexological stimulation is unaffected by pseudo-information: a functional magnetic resonance imaging study","volume":"13","author":"N Miura","year":"2013","journal-title":"BMC Complement Altern Med"},{"issue":"1","key":"pone.0327865.ref042","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.neulet.2008.10.022","article-title":"Somatotopical relationships between cortical activity and reflex areas in reflexology: A functional magnetic resonance imaging study","volume":"448","author":"T Nakamaru","year":"2008","journal-title":"Neurosci Lett"},{"key":"pone.0327865.ref043","doi-asserted-by":"crossref","first-page":"1727479","DOI":"10.1155\/2022\/1727479","article-title":"The Effects of Foot Reflexology for Smoking Cessation on Brain Activities with Functional Magnetic Resonance Imaging (fMRI): A Pilot Study","volume":"2022","author":"P Wattanaruangkowit","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"issue":"9","key":"pone.0327865.ref044","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jmpt.2014.09.001","article-title":"Immediate changes after manual therapy in resting-state functional connectivity as measured by functional magnetic resonance imaging in participants with induced low back pain","volume":"37","author":"CW Gay","year":"2014","journal-title":"J Manipulative Physiol Ther"},{"key":"pone.0327865.ref045","doi-asserted-by":"crossref","first-page":"102677","DOI":"10.1016\/j.msksp.2022.102677","article-title":"Avoiding nocebo and other undesirable effects in chiropractic, osteopathy and physiotherapy: An invitation to reflect","volume":"62","author":"D Hohenschurz-Schmidt","year":"2022","journal-title":"Musculoskelet Sci Pract"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0327865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T17:42:05Z","timestamp":1753724525000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0327865"}},"subtitle":[],"editor":[{"given":"Federico","family":"Giove","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0327865","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]}}}