Altered sensory, pain perceptions observed in cEDS patients

Study probes characteristics of pain in classical Ehlers-Danlos syndrome

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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An illustration shows a person with joint pain lying on couch.

Chronic pain was prevalent among people with classical Ehlers-Danlos syndrome (cEDS), strongly affecting life quality and emotional health, according to a recent study.

cEDS patients also exhibited abnormal sensory perceptions and heightened pain responses compared with healthy people.

The authors, who touted the study as the first to systematically evaluate pain in people with a hereditary connective tissue disease, believe the findings indicate “altered neural function in cEDS,” although more studies are needed.

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The study, “Sensory profiling in classical Ehlers-Danlos syndrome: a case-control study revealing pain characteristics, somatosensory changes, and impaired pain modulation,” was published in The Journal of Pain.

cEDS is the most common type of Ehlers-Danlos syndrome (EDS) with a known genetic cause. The disorder is characterized by overly mobile joints, stretchy and fragile skin, and abnormal wound healing that most often arise from mutations in the COL5A1 or COL5A2 genes that encode parts of type 5 collagen, a connective tissue protein.

Pain is a major complaint for many people with various types of EDS and other connective tissue diseases.

In previous questionnaire studies, more than 70% of cEDS patients reported they experienced chronic pain, according to the authors. Moreover, preclinical studies have identified abnormal pain responses in a mouse model of the disease.

Still, there is a lack of information about the characteristics of patients’ pain and the mechanisms underlying it.

“This major gap in the study of pain in EDS also hampers the development of effective treatment strategies for these individuals in whom the high use of analgesics, surgery, and physical therapy, brings only modest relief at best and is frequently associated with unwanted side effects,” the researchers wrote.

Pain profile and sensory perceptions

In the study, the researchers aimed to investigate the pain profile and sensory perceptions (somatosensory characteristics) in people with cEDS relative to healthy people.

Nineteen cEDS patients — 13 women and six men — underwent quantitative sensory testing and completed validated questionnaires related to pain, as did 19 age- and sex- matched healthy people without a history of chronic pain, who served as a control group.

Of the cEDS patients, 11 had a history of taking pain relievers for musculoskeletal pain, and five took them on a daily basis at the time of testing.

Clinically relevant pain was common in cEDS patients. Specifically, 32% of patients reported their average pain severity was at least a five on a scale of 10 in the last month.

Pain was generally localized to a limited number of joints or the lower back, although some patients reported more generalized pain. Signs of neuropathic pain, or pain arising from nerve damage, were not reported consistently.

Findings from a battery of other questionnaires indicated that patients had lower physical activity levels, greater daily life limitations, and a lower health-related quality of life than the control group.

They also were found to be more aware of and vigilant about feelings of pain, and more fearful of injury due to movement.

Somatosensory testing

Somatosensory testing involved measuring a person’s sensitivity to electric stimulation, temperature, vibration, or pressure in various areas of the body. Participants were asked to refrain from exercise, caffeine, nicotine, alcohol, and certain pain medications prior to sensory testing, all of which can influence pain perceptions.

cEDS patients were found to have an altered sensory profile. Specifically, they had a higher threshold than healthy people for perceiving vibrations in the ankles.

The researchers interpreted that to mean cEDS patients may have hypoesthesia, or reduced sensations controlled by the peripheral nerves that communicate between the brain and body.

cEDS patients exhibited paradoxical thermal sensations, or difficulty distinguishing between hot and cold stimuli. They also had hyperalgesia, or increased pain sensitivity to pressure or cold temperature in the limbs, compared with control participants.

Anti-nociceptive responses — the body’s natural mechanisms to manage feelings of pain — were diminished in cEDS patients relative to healthy people, again suggesting impaired pain modulation.

While the findings will require validation in future studies, scientists believe they support a hypothesis that disturbances to the extracellular matrix (ECM) leads to changes in somatosensory perception.

The ECM is a collection of proteins, including collagen, that gives tissues their structure and are disturbed in connective tissue diseases like cEDS. Recent evidence has indicated that ECM reorganization might contribute to pain.

The data here offer “interesting new insights on the possible role of the ECM in the development and persistence of pain,” the scientists wrote. “More in depth and mechanistic investigations … are warranted to better understand the mechanisms underlying the observed changes in somatosensory perception in cEDS.”