Pain in Ehlers-Danlos Syndrome: Why It’s So Complex and How to Understand It

If you live with Ehlers-Danlos Syndrome (EDS) or a Hypermobility Spectrum Disorder (HSD), you already know something most people don’t: pain is rarely straightforward. It shifts. It spreads. It changes character. It refuses to match what imaging shows. And sometimes, it makes you feel like your body is sending mixed signals on purpose.

There’s a reason for that.

Pain in EDS is driven by multiple mechanisms, not just one. The connective tissue is different. The nervous system behaves differently. Joints move differently. Muscles work differently. And the brain learns all of this over time.

Understanding which mechanism is driving your pain is the key to choosing the right treatments — and finally feeling like you have a roadmap instead of a guessing game.

Modern pain science identifies three major categories of pain. People with EDS often experience all three at the same time:

• Nociceptive pain

• Neuropathic pain

• Nociplastic pain / Central sensitization

Below is a clear, human-centered breakdown of what each means and how they show up in your body.

Why Pain in EDS Is So Complicated

EDS affects collagen, the protein that gives tissues strength and structure. When collagen is more elastic or fragile than it should be, several things happen at once:

• Joints become unstable

• Ligaments can’t provide adequate control

• Muscles try to compensate

• Nerves get irritated

• The central nervous system becomes overprotective

This is why a simple label like “chronic pain” doesn’t capture what’s actually happening.

You are often dealing with layered pain, each mechanism influencing the next.

Nociceptive Pain: When Tissues Are Stressed or Overworked

What It Is

Nociceptive pain comes from the body’s tissues — joints, ligaments, tendons, fascia, muscles — when they’re irritated, strained, or overused.

Why It’s So Common in EDS

Because connective tissue is more elastic, joints move more than they should. This leads to:

• Recurrent subluxations or dislocations

• Ligament microtears

• Tendon strain

• Muscle guarding

• Trigger points from chronic overuse

• Early degenerative changes

Research confirms that people with hypermobile EDS experience significantly higher rates of musculoskeletal pain because of joint instability alone.¹

How It Feels

People often describe nociceptive pain as:

• Aching

• Throbbing

• Sharp with movement

• Localized to a joint or region

What Helps (From a Physical Therapy Perspective)

Nociceptive pain often improves with:

• Gentle, progressive strengthening

• Motor control training

• Joint stabilization

• Reducing end-range movement

• Temporary bracing or taping

• Reducing repetitive strain

At Actify PT in Boca Raton, this layer is often the starting point, because if joints don’t feel supported, nothing else will move in the right direction.

Neuropathic Pain: When Nerves Become Irritated or Compressed

What It Is

Neuropathic pain happens when the somatosensory nervous system is irritated, compressed, or injured.

Why EDS Creates Neuropathic Pain

Hypermobile joints can shift just enough to alter the mechanical environment around nerves. Common contributors include:

• Nerve stretching during subluxations

• Nerve compression from unstable joints

• Thoracic outlet–type symptoms

• Cervical instability causing neural tension

• Scar tissue tethering nerves

• Small fiber neuropathy (SFN), increasingly recognized in hEDS²

How It Feels

Neuropathic pain has a distinct “nerve-like” signature:

• Burning

• Electrical

• Sharp or shooting

• Tingling or numbness

• Pain following a narrow line or pathway

• Sensitivity to touch in specific regions

What Helps

Neuropathic pain responds best to strategies that reduce mechanical and chemical irritation:

• Improving joint alignment

• Cervical and scapular stabilization

• Gentle nerve gliding (when appropriate)

• Postural decompression

• Medical approaches that target nerve signaling

For many patients with EDS, identifying the nerve component is a game-changer, because muscle strategies alone won’t calm nerve-related pain.

Central Sensitization / Nociplastic Pain: When the Nervous System Turns Up the Volume

What It Is

The nervous system becomes hypersensitive, amplifying pain signals beyond what makes sense.

• Central sensitization: the spinal cord and brain become over-responsive

• Nociplastic pain: pain from altered nociception without tissue damage or clear nerve injury³

Why EDS Is Highly Associated With Sensitization

Research shows people with hEDS have:

• Lower pain thresholds

• Increased “wind-up” (heightened spinal cord response)

• Sensory hypersensitivity

• More widespread pain patterns

How It Shows Up

Common symptoms include:

• Widespread or migrating pain

• Pain that doesn’t match imaging

• Allodynia (pain from light touch)

• Hyperalgesia (stronger-than-expected pain)

• Fatigue, brain fog, sleep disruption

• Unpredictable flare-ups

Why It Happens

Years of:

• Instability

• Tissue irritation

• Nerve irritation

• Fear-driven bracing

• Poor sleep

• Autonomic dysfunction

... teach the nervous system to stay in “high alert,” even when no active injury is present.

This mechanism does not mean your pain is exaggerated or psychological. It means your nervous system has been trained by experience and it can be retrained.

Real Talk: Most People with EDS Have “Mixed Mechanism” Pain

You are not dealing with one pain mechanism. You’re dealing with:

• Mechanical joint pain

• Nerve irritation

• Nervous system amplification

This is why treatments that focus on only one layer often fail. A holistic plan must address all three mechanisms to create meaningful change.

How to Tell Which Type of Pain You’re Experiencing

Clues for Nociceptive Pain

• Clearly tied to movement or posture

• Localized to a joint or muscle

• Feels better with stability or support

Clues for Neuropathic Pain

• Burning, electric, or shooting

• Numbness or tingling

• Follows a nerve distribution

Clues for Nociplastic / Central Sensitization

• Widespread or unpredictable

• Worse with stress, illness, or sensory overload

• Not explained by imaging

• Paired with fatigue or brain fog

A validated assessment called the Central Sensitization Inventory (CSI) can help identify the nociplastic component.⁴

Treatment Strategies for Each Pain Mechanism

If Pain Is Mostly Nociceptive

• Strengthening for joint stability

• Motor control training

• Manual therapy

• Reducing end-range movement

• Pacing physical activity

If Pain Is Mostly Neuropathic

• Improving joint alignment

• Nerve gliding when appropriate

• Scapular and cervical stabilization

• Posture modification

• Medical approaches targeting nerve irritability

If Pain Is Mostly Nociplastic

• Graded exposure to movement

• Gentle aerobic conditioning

• Sleep optimization

• Stress and autonomic regulation

• Pain neuroscience education

• ACT-based cognitive strategies

At Actify PT, patients typically need all three — but in different ratios depending on their underlying physiology.

Why Understanding Mechanisms Changes Everything

When you finally understand why your pain behaves the way it does, you can choose treatments tailored to the biology instead of hoping something helps.

A patient in Boca Raton with sharp, localized rib pain (nociceptive) needs different tools than someone whose burning leg pain follows a nerve pattern (neuropathic), or someone whose pain is widespread and unpredictable regardless of imaging (nociplastic).

Knowing the mechanism is the difference between chasing symptoms and creating long-term change.

Summary

Pain in EDS is not random, mysterious, or “in your head.” It is a reflection of how connective tissue, nerves, and the central nervous system interact over time.

Most people with EDS experience a blend of:

• Nociceptive (tissue) pain

• Neuropathic (nerve) pain

• Nociplastic (sensitized) pain

Understanding these mechanisms helps you choose better treatments and finally feel like your body makes sense, not because the pain disappears overnight, but because you’re no longer fighting in the dark.

References

1. Tinkle, B. et al. (2021). Hypermobile Ehlers-Danlos Syndrome. GeneReviews. https://www.ncbi.nlm.nih.gov/books/NBK1279/

2. Oaklander, A. L., & Klein, M. M. (2013). Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset widespread pain syndromes. Pediatrics.

3. International Association for the Study of Pain. (n.d.). Terminology. https://www.iasp-pain.org/resources/terminology/

4. Mayer, T. G., Neblett, R., Cohen, H. et al. (2012). The Development and Psychometric Validation of the Central Sensitization Inventory. Pain Practice. https://onlinelibrary.wiley.com/doi/abs/10.1111/papr.13411

Disclaimer

This blog is for educational purposes only and does not replace individualized medical advice. Always consult a licensed healthcare provider or a physical therapist experienced in EDS before starting any new exercise, treatment plan, or pain management strategy.