Emerging Clinical Concepts in Pain Management of Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome (EDS) is a congenital connective tissue disorder that is often marked by chronic pain and considerable functional impairment. Pain in EDS is typically multifaceted, involving musculoskeletal, neuropathic, autonomic, and centralized pain components. The present investigation, therefore, aims to examine common pain phenotypes and mechanisms in EDS and to discuss strategies for interdisciplinary pain management briefly.

Recent studies have identified multiple sources of pain etiologies in EDS, including joint instability, repetitive microtrauma, small fiber neuropathy, and dysfunctional central pain processing. There is also growing evidence that nociceptive pain mechanisms and psychological factors may play a role in pain experience. Furthermore, current literature promotes multidisciplinary care models that synthesize physical therapy targeting joint stabilization and neuromuscular control, symptom-specific pharmacologic therapy, and psychological interventions. In addition, recent studies have investigated complementary therapies, including trigger-point injections, that may provide benefit. Despite this, high-quality evidence supporting interventional and specific pharmacologic regimens remains sparse. EDS pain remains multifaceted and requires an individualized and mechanism-informed approach to treatment. Integrated care models that include rehabilitation, phenotype-guided pharmacotherapy, and behavioral interventions form the bedrock of management. Ongoing research is necessary to refine phenotype-driven treatment strategies further.