Sensory profiling in classical Ehlers-Danlos syndrome: a case-control study revealing pain characteristics, somatosensory changes, and impaired pain modulation

Abstract

Pain is one of the most important, yet poorly understood complaints in heritable connective tissue disorders (HCTD) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for Ehlers-Danlos syndromes (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (VAS ≥5/10 in 32% for average pain intensity the past month) and worse health -related quality of life. Altered sensory profile was found in the cEDS group with higher (p=0.04) detection thresholds for vibration stimuli at the lower limb indicating hypoesthesia, reduced thermal sensitivity with more (p<0.001) paradoxical thermal sensations, and hyperalgesia with lower pain thresholds to mechanical (p<0.001) stimuli at both the upper and lower limbs and to cold (p=0.005) stimulation at the lower limb. Using a parallel conditioned pain paradigm, the cEDS group showed significantly smaller antinociceptive responses (p-value between 0.005 and 0.046) suggestive of impaired endogenous central pain modulation. In conclusion, Individuals with cEDS report chronic pain and worse health-related quality of life, and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights on the possible role of the ECM in the development and persistence of pain.

Central Sensitivity Symptoms and Autistic Traits in Autistic and non-Autistic Adults

“…Eccles et al, 2020;Sharp et al, 2021), and autistic women in particular are more likely to be diagnosed with EDS than the general population (Casanova et al, 2020;Ward et al, 2023). There is also some research suggesting that sensory sensitivity is directly related to connective tissue differences (Casanova et al, 2020;Colman et al, 2023;Csecs et al, 2022;Savage et al, 2021). More research is therefore needed to understand whether sensory sensitivity is an independent risk factor for developing a CSS (Bar-Shalita et al, 2019), or an artifact of an underlying genetic connective tissue difference.…”