What are the management options for Ehlers-Danlos (Ehlers-Danlos Syndrome) pain?

Management of Ehlers-Danlos Syndrome Pain

Pain management in Ehlers-Danlos syndrome requires a structured approach starting with physical therapy and bracing, followed by neuromodulators for neuropathic pain, while avoiding opioids except in severe refractory cases, and integrating cognitive behavioral therapy to address the high burden of anxiety and central sensitization that amplifies pain in these patients. 1, 2

First-Line Non-Pharmacologic Interventions

Occupational therapy and bracing are the most effective initial treatments, with 70% of patients reporting improvement. 3 Physical therapy should focus on:

• Strengthening exercises to stabilize hypermobile joints and prevent subluxations/dislocations 4
• Proprioceptive training to address the underlying proprioceptive disorders that contribute to pain 4
• Graded exercise programs that avoid triggering kinesiophobia while maintaining function 2
• Compression garments to provide joint stability and reduce pain 4

The AGA emphasizes that exercise training is a core component of management, particularly when POTS (postural orthostatic tachycardia syndrome) coexists with EDS 1

Pharmacologic Management Algorithm

Step 1: Acetaminophen and NSAIDs

• Start with acetaminophen for mild-to-moderate musculoskeletal pain as first-line due to favorable safety profile 5
• NSAIDs are second-line for inflammatory joint pain, but use cautiously given GI, renal, and cardiovascular risks 5
• NSAIDs were commonly used (70-92% of patients) but showed variable efficacy 6

Step 2: Neuromodulators for Neuropathic Pain

Neuropathic modulators (tricyclic antidepressants, gabapentin, pregabalin, SNRIs) should be used for neuropathic pain and central sensitization, which develops as EDS progresses 1, 2, 4

• The AGA specifically recommends tricyclic antidepressants, SSRIs, SNRIs, pregabalin, and gabapentin for abdominal pain in EDS patients 1
• Important caveat: 47% of patients report adverse effects with neuropathic modulators, making them the least well-tolerated medication class 3

Step 3: Muscle Relaxants and Antispasmodics

• Muscle relaxants can be used for muscle-related pain from joint instability 3
• Antispasmodics (hyoscyamine, dicyclomine, peppermint oil) are appropriate for GI pain, which affects 98% of EDS patients 1

Step 4: Opioids - Use With Extreme Caution

Opioids should be avoided or used only as last resort in severe refractory pain, despite being rated as "extremely helpful" by 10-24% of users 1, 6

• The AGA explicitly states: "Caution with opiates is advocated, and opiates should not be used specifically to treat abdominal pain" 1
• The concern is that opioids can trigger mast cell activation in patients with comorbid MCAS (mast cell activation syndrome) 1
• When used, combine with comprehensive multidisciplinary care 2

Addressing Comorbid Conditions

POTS Management (Present in Many EDS Patients)

Treat POTS symptoms with lifestyle modifications first, then pharmacotherapy: 1

• Increase fluid and salt intake (dietary salt, salt tablets) 1
• Compression garments for lower extremities 1
• Pharmacologic options: fludrocortisone (volume expansion), propranolol or ivabradine (heart rate control), midodrine (vasoconstriction) 1

MCAS Management (Triggers Pain Flares)

When MCAS is suspected, use histamine receptor antagonists and mast cell stabilizers: 1

• H1 and H2 receptor antagonists as first-line 1
• Avoid triggers: NSAIDs, opioids, temperature changes, emotional stress, certain foods 1
• This is critical because MCAS degranulation releases inflammatory mediators that amplify pain 1

Psychological and Behavioral Interventions

Cognitive behavioral therapy is essential, not optional, because: 2, 7

• EDS patients have high rates of anxiety, panic disorders, and kinesiophobia that amplify pain perception 2
• Central sensitization develops over time, making psychological approaches critical for pain modulation 2, 4
• Pain self-management programs combining CBT, coping strategies, and relaxation techniques showed significant improvement in two case reports 2

Complementary Therapies

Complementary therapies are used by 56% of EDS patients, particularly those with higher pain levels: 6

• Marijuana was rated as one of the most efficacious treatments (10-24% rated "extremely helpful") 6
• Traditional Chinese therapies and herbal medications are commonly tried but lack robust efficacy data 6
• Low-dose naltrexone, TENS units, and laser therapy show promising effects in recent literature 7

Interventional Approaches

Trigger point injections can be considered for localized myofascial pain, but avoid extensive procedures given tissue fragility: 7

• The concern about local anesthetic resistance in EDS is unwarranted - appropriate pain interventions can decrease pain intensity 2
• Surgery should be minimized due to tissue fragility and poor wound healing 4

Critical Pitfalls to Avoid

• Do not rely solely on medications - approximately 90% of EDS patients have chronic pain that requires multimodal management 2, 4
• Do not use ice water immersion or continuous fans for pain relief, as these cause tissue damage, ulcerations, and rebound worsening 1
• Do not prescribe opioids as first-line despite patient requests - focus on addressing underlying mechanisms 1
• Do not ignore GI symptoms - 98% of EDS patients meet criteria for disorders of gut-brain interaction, which contribute to overall pain burden 1
• Do not treat pain in isolation - address hypermobility, central sensitization, fatigue, and psychological comorbidities simultaneously 7