{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:15:49Z","timestamp":1793646949622,"version":"4.5.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Although pain is a common complication of the hypermobile type of Ehlers\u2013Danlos syndrome, its underlying mechanisms are still an issue of controversy. In this psychophysical study, we aimed at testing small-fiber function and the endogenous pain inhibitory control in patients with pain due to Ehlers-Danlos syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In 22 patients with pain due to Ehlers-Danlos syndrome and 22 healthy participants, matched for age and sex, we tested small-fiber function using quantitative sensory testing and the endogenous pain inhibitory control using the conditioned pain modulation (CPM) protocol. As quantitative sensory testing methods, we included thermal pain and mechanical pain thresholds and the wind-up ratio. The CPM protocol consisted of two heat painful stimuli, that is, a test stimulus and a conditioning stimulus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All patients complained of widespread pain. Quantitative sensory testing revealed no small-fiber deficit; in the area of maximum pain, we found an increased wind-up ratio. Whereas in the healthy participants the CPM protocol showed that the test stimulus rating was significantly reduced during conditioning, in patients with pain due to hEDS, the test stimulus rating increased during conditioning.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our psychophysical study showing that patients with pain due to hEDS have an increased wind-up ratio in the area of maximum pain and abnormal CPM protocol suggests that in this condition, pain is associated with central sensitization, possibly due to deficit of the endogenous pain inhibitory control. These data might be relevant to pharmacological treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/pm\/pnaa038","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T12:08:30Z","timestamp":1580126910000},"page":"1929-1935","source":"Crossref","is-referenced-by-count":34,"title":["Pain due to Ehlers-Danlos Syndrome Is Associated with Deficit of the Endogenous Pain Inhibitory Control"],"prefix":"10.1093","volume":"21","author":[{"given":"Caterina Maria","family":"Leone","sequence":"first","affiliation":[{"name":"Department of Human Neuroscience, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Celletti","sequence":"additional","affiliation":[{"name":"Department of Physical medicine and Rehabilitation, Sapienza University, Rome, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Camerota","sequence":"additional","affiliation":[{"name":"Department of Physical medicine and Rehabilitation, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Truini","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"issue":"1","key":"2020101310145166400_pnaa038-B1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am J Med Genet C Semin Med 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