Endogenous pain modulation in the Ehlers–Danlos syndrome, hypermobility type

Abstract

Purpose: The Ehlers-Danlos Syndrome (EDS) is the most prevalent heritable connective tissue disorder. More than 90% of individuals are classified as having the hypermobility type (EDS-HT). Patients typically demonstrate generalized severe joint hypermobility, which is frequently associated with recurrent joint dislocations and premature osteoarthritis. Although pain is the number one complaint in EDS-HT, causing severe disability in daily life, the underlying pain mechanisms and the nature of pain are unknown. Therefore, this study aims to assess the nature of pain (nociceptive / neuropathic / dysfunctional pain) and the endogenous pain modulation in EDS-HT. Methods: Twenty-one patients with EDS-HT were compared with 20 healthy control subjects (CON), and 11 fibromyalgia patients (FM). The latter was included, because FM has been the subject of a lot of research regarding endogenous pain modulatory deficits, and because of the large symptomatic overlap with EDS-HT. All patients filled out a Margolis Pain Diagram, the Pain Detect Questionnaire (PDQ) and questionnaires regarding cognitive-emotional sensitization (Pain Catastrophizing Scale - PCS, Hospital Anxiety and Depression Scale - HADS, Tampa Kinesiophobia Scale - TSK, Pain Vigilance and Awareness Scale – PVAQ). After a thorough anamnesis regarding medical history, the somatosensory system was evaluated. Thermal quantitative sensory testing was performed on the right trapezius and left tibialis anterior to determine the sensory thresholds for cold and warmth, and the pain thresholds for cold and heath. Next, pressure pain thresholds were examined on the right trapezius and quadriceps. Further, endogenous pain modulation was assessed by evaluating wind-up (WU), conditioned pain modulation (CPM) and exercise induced analgesia (EIA). WU was assessed by applying 10 pressure stimuli (at the pressure pain threshold) on the trapezius and quadriceps and by evaluating the subsequent increase in VAS score. CPM was induced by immersing the left hand into a 46° water bath and evaluating the subsequent decrease in VAS score (for a pressure stimulus at the pressure pain threshold). EIA was assessed by comparing the pressure pain threshold before and after a submaximal bicycle test (Aerobic Power Index Test). Results: Regarding the nature of pain, the EDS-HT group showed characteristics of neuropathic pain, with 89.5% of patients being classified by the PDQ as having possible or probable neuropathic pain. In addition, the EDS-HT group also showed characteristics of dysfunctional pain. The Margolis pain diagram showed a more widespread pain in patients with EDS-HT (p<0.001). WU at the trapezius was significantly higher in patients with EDS-HT and FM compared to controls (p=0.046). EIA was significantly reduced at the quadriceps in EDS and FM (p=0.041). By contrast, CPM did not significantly differ between groups (p=0.903). Cognitive emotional sensitization was present in the EDS-HT group (significantly higher scores on the PCS, HADS and TSK compared to controls; p <0.01). Conclusion: Patients with EDS-HT suffer from nociceptive, as well as neuropathic and dysfunctional pain. The endogenous pain modulation is disrupted by a reduced pain inhibition, which is comparable to FM.