Introduction

Ehlers-Danlos syndrome (EDS) is a group of disorders that are transmitted from parent to child when one parent has the gene (autosomal dominant cases) or when both parents have the gene (autosomal recessive). 

Both children and adults suffer from a variety of symptoms that cause severe pain and a low quality of life. 

You may be unfamiliar with this condition, a medical student seeking a deeper understanding, or simply someone interested in learning more. You may also have wondered why EDS often causes chronic pain and what treatment options are available. This article explores the mechanisms behind chronic pain in Ehlers-Danlos syndrome and outlines the current approaches to managing it.

Understanding ehlers-danlos syndrome

EDS is caused by an abnormality in the connective tissue of the body. It is rare, affecting about 1 in every 5,000 to 250,000 individuals.¹

There are different types of connective tissues in the body, which form a framework that holds everything together. It supports, protects, and joins other parts of the body together. Think of it like a glue with the perfect consistency and contents that help support and keep your body together.

When your glue does not hold well, it falls apart. But in EDS, it is more than just falling apart. Any organ can be affected with symptoms ranging from mild to very severe, some of which are:²

• Skin fragility 
• Skin hyperextensibility (when the skin is too flexible, doughy)
• Atrophic scarring (deep pits in skin)
• Joint hypermobility
• Common joint dislocations
• Easy bruising
• Pain 

However, amongst the 14 subtypes of the disease, hypermobile EDS (hEDS) is the most common, with chronic pain being the most severe and harmful symptom, causing those affected to be hospitalised.²

Although this chronic pain is the most common symptom, the mechanisms causing it are not well researched, making management and treatment difficult. 

Burdens of chronic pain in ehlers-danlos syndrome 

Chronic pain is common amongst individuals affected with this connective tissue disease, affecting 9 out of 10 individuals in every case. 

According to Chopra and colleagues in an article published in the American Journal of Medicine, “Chronic pain is one of the major symptoms presented by patients with hEDS. It often presents as diffuse body pain affecting almost every part of the body. It is common and may be severe. In one study, the prevalence of chronic pain was 90% in patients with various types of EDS, with the highest scores on severity of pain found in hEDS.”³

Sinceit can affect any part of the body and any organ, most individuals are faced with disability in performing normal daily activities, which results ina decreased quality of life. 

Most affected with the disease, both children and adults describe the pain as “growing pains”, increasing in severity over time.⁴ 

Individuals suffering from EDS also often face an emotional toll, experiencing anxiety and depression due to their chronic pain and the challenges in obtaining a diagnosis, with an average time of 10 years. 

Hence, it is necessary to understand the mechanisms underlying the cause of this pain, as well as treatment strategies.

What are the mechanisms of chronic pain in EDS? 

There is no single mechanism that can explain the origin of chronic pain in Ehlers-Danlos syndrome because different areas in the body may or may not be affected. However, a few common pathways can be noted:

Musculoskeletal causes

Many EDS patients experience pain in their muscles and joints, especially those classified as having hypermobility (when joints and muscles can stretch far beyond normal limits), as seen in hEDS. It is often the first sign of chronic pain; some of the major highlighted pathways include:⁵

Joint Instability

This is due to the excessive flexibility of the joints and ligaments. This is also known as congenital capsuloligamentous laxity (CCL). It leads to frequent dislocations and soft tissue injuries of different body parts and is one of the main sources of chronic pain in EDS.

Proprioception 

Proprioception is the simple ability to know the location of a specific part of your body in relation to other parts. It is often known as our “sixth sense” and is unfortunately reduced in people with EDS. So they can't always tell where their body is. Hence, balance problems, more falls and increased pain.⁴

Muscle Weakness

Studies have also shown that muscle weakness caused by muscle hypotonia (low tone) is responsible for chronic pain in EDS patients.⁵

Neuropathic mechanisms

This occurs when there is damage to the nerve fibers responsible for sending or receiving information from different parts of the body. It can be caused by:^4,5

Nerve compression 

When nerves in different parts of the body are pressed or squeezed by surrounding structures, it can lead to nerve damage and severe pain in that area and its surrounding structures. The most common areas of nerve compression in EDS patients are in the arms and cervical spine. 

Central sensitization

Another major contribution to chronic pain in Ehlers-Danlos syndrome is central sensitisation. This process involves the brain and spinal cord becoming overly sensitive to pain. So a fall, pinch, or minor injury becomes heightened, generalised, and lasts for a very long period.

Small fiber neuropathy 

The destruction of normal pain fibers contributes to neuropathic pain. When damage in EDS prevents their regulation, patients experience numbness and tingling (paraesthesia) and feel excessive pain in response to sensations that are not normally painful (hyperalgesia).

Psychosocial factors

Emotions like fear and anxiety can make pain feel worse and more likely to become chronic. People with EDS or hypermobility often avoid activities because they fear pain or injury, leading to : 

• Muscle weakness
• Increase in disability 
• Increased pain 
• Decreased pain tolerance 
• Depression 
• Sleep disturbance 
• Chronic fatigue 

What are the treatment strategies?

Treatment of EDS is not a straight path; it requires a multimodal approach with a multidisciplinary team (a group of different healthcare professionals).⁶ 

This is because EDS is a complex disease that involves symptoms affecting the muscles, bones, head, neck, and even internal organs such as the stomach. 

Current treatment strategies include: 

Pharmacological approaches

For acute short-lasting pain, most individuals with EDS are treated with non-steroidal anti-inflammatory drugs (NSAIDs) such as acetaminophen (paracetamol), ibuprofen, and diclofenac at full dosage. 

Minor opioids like tramadol and codeine may be used together with NSAIDs. Opioids are stronger pain medications, but are generally discouraged due to the side effects.

For more severe, widespread body pain (fibromyalgia), chronic neuropathic and musculoskeletal pain, drugs like pregabalin, duloxetine, and milnacipran are the FDA-approved medications. 

For symptoms like muscle cramps, muscle relaxants are used.

Physiotherapy & exercise

Due to muscle weakness and overflexibility, physical therapy in EDS is focused on stabilising the joints, strengthening the muscles, and enhancing proprioception. So far, this has proven to be one of the most effective management strategies, especially in hEDS.^5,6

Some of the most successful pain relief physical therapy methods include the use of:^3,6

• Chiropractic therapy
• Splints 
• Body braces 
• Massage therapy 
• Gentle stretching exercise
• Core and trunk strengthening 

It is important to note that exercise and physiotherapy for the treatment of EDS cannot be aggressive, as this could lead to more damage than good.⁵ 

Psychological & behavioural therapies

Individuals suffering from chronic pain are often affected by psychosocial disturbances like depression, anxiety, fear, and withdrawal. 

Some behavioural therapies have been explored to promote wellness and improve pain; a systematic review analysed studies exploring these therapies, showing that they provide great relief in alleviating chronic pain and mental health problems in those suffering from EDS.

Some of these strategies include the following:^[7]

Cognitive-behavioural therapy (CBT)

A form of psychotherapy that allows an individual to explore and highlight their challenges, and ultimately discover tools and methods that may help solve them. 

Dialectical behavioural therapy (DBT)

This is a form of CBT that utilises open awareness of one's thoughts and feelings, regulates emotions, and increases tolerance of discomfort to reduce pain. 

Intensive interdisciplinary treatment programs (IIPT)

This method treats chronic pain by combining emotional and physical care. It involves combining physical therapy, cognitive behavioural therapy, and medication management with good nutrition and enjoyable leisure activities, such as art, for a prolonged period, ranging from 6 weeks to years. 

Acceptance and commitment therapy (ACT)

This is used when the traditional CBT does not work; it is focused on encouraging individuals to embrace their disability and learn to use it. 

Please note that this is only for information purposes; you should seek professional help and advice if you face any symptoms or have any further enquiries.

Challenges and gaps in management 

Several challenges and gaps in the management of chronic pain in Ehlers-Danlos syndrome can be highlighted.⁶ 

• Although strategies for pain relief in EDS may offer brief or short-term relief, especially for children, there is still a major limitation 
• Most of the pharmacological approaches are not effective for chronic pain in EDS
• There is a lack of standardised protocols or guidelines to manage pain 
• There is a need for more clinical trials to be conducted to test the effectiveness of new drugs 

Summary 

• Chronic pain in individuals with Ehlers-Danlos syndrome, especially hEDS, is complex and involves different mechanisms
• Individuals suffering from this disease are often misdiagnosed or not diagnosed early enough due to its different symptoms 
• Traditional pharmacological treatments are not enough to provide pain relief because they may not target the underlying mechanism
• Psychosocial therapies in combination with physical therapy may be the best-suited strategy for providing pain relief
• A holistic approach to pain management is required, incorporating a multidisciplinary team
• Looking forward, more clinical trials and research are needed to provide standardised treatment plans