From the Guidelines
Ehlers-Danlos syndrome (EDS) contributes to nociplastic pain conditions through a complex interplay of connective tissue fragility, central sensitization, proprioceptive dysfunction, autonomic nervous system dysregulation, and mast cell activation syndrome, ultimately leading to a self-reinforcing cycle of peripheral tissue vulnerability and central nervous system sensitization. The primary mechanism involves connective tissue fragility due to defective collagen synthesis, which leads to joint hypermobility and microtraumas that repeatedly activate nociceptors, as seen in various pain conditions including complex regional pain syndrome 1. This persistent nociceptive input eventually causes central sensitization, where the central nervous system becomes hyperresponsive to both painful and non-painful stimuli, a key characteristic of nociplastic pain conditions 1. Some key points to consider in the mechanism of EDS-related nociplastic pain include:
- Connective tissue fragility and joint hypermobility leading to microtraumas and repeated nociceptor activation
- Central sensitization and hyperresponsiveness to painful and non-painful stimuli
- Proprioceptive dysfunction and abnormal movement patterns contributing to further tissue stress
- Autonomic nervous system dysregulation and sympathetic overactivity amplifying pain perception
- Mast cell activation syndrome and the release of inflammatory mediators directly stimulating nociceptors These mechanisms create a complex pain cycle where peripheral tissue vulnerability and central nervous system sensitization reinforce each other, making nociplastic pain particularly challenging to manage in EDS patients, and highlighting the need for a comprehensive treatment approach that addresses both the physical and psychological aspects of pain 1.
From the Research
Mechanism of Nociplastic Pain in Ehlers-Danlos Syndrome
The mechanism by which Ehlers-Danlos syndrome (EDS) contributes to nociplastic pain conditions is complex and multifactorial. Key factors include:
- Joint subluxations and dislocations, previous surgery, muscle weakness, proprioceptive disorders, and vertebral instability 2
- Central sensitization of pain signals, which can lead to chronic myofascial pain and neuropathies 3
- Generalized body pain, fatigue, headaches, gastrointestinal pain, temporomandibular joint pain, dysmenorrhea, and vulvodynia, which can contribute to the development of nociplastic pain 2
Underlying Causes of Pain in EDS
The underlying causes of pain in EDS are diverse and include:
- Defective collagen synthesis, leading to joint hypermobility, skin extensibility, and tissue fragility 3, 4
- Musculoskeletal pain, which is mentioned in the diagnostic criteria and described as early in onset, chronic, and debilitating 5
- Hypermobile joints, dislocations, and previous surgery, which can contribute to pain severity and functional impairment 5
Prevalence and Impact of Pain in EDS
Pain is a common and severe manifestation of EDS, with: