• Caterina Maria Leone, Claudia Celletti, Gianfranco Gaudiano, Paola Anna Puglisi, Alessandra Fasolino, Giorgio Cruccu, Filippo Camerota, and Andrea Truini.
• Department of Human Neuroscience, Sapienza University, Rome, Italy.
• Pain Med. 2020 Sep 1; 21 (9): 1929-1935.

ObjectivesAlthough pain is a common complication of the hypermobile type of Ehlers-Danlos 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.MethodsIn 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.ResultsAll 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.ConclusionsOur 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.© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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