This document discusses pain in patients with Ehlers-Danlos syndrome. It finds that while pain was expected to be mainly nociceptive from joint damage, preliminary findings suggest it is often neuropathic in nature. Various diagnostic tests did not find neurological lesions to explain the pain. Questionnaires found the pain pattern was similar to fibromyalgia, with widespread pain accompanied by fatigue, unusual sensations, and other health problems impacting daily life. The pathophysiology of pain in Ehlers-Danlos may be more complex than expected, potentially involving chronic inflammation and central sensitization rather than solely musculoskeletal involvement.

1. Dolore in corso di Sindrome di
Ehlers Danlos – Variante ipermobile
A Truini
Department of Neurology and Psychiatry, Sapienza University, Rome
Disclosure: No conflict of interest to declare

2. Anatomia e Fisiologia del
Sistema Nocicettivo

3. Five types of pain
•
•
•
•
•
Nociceptive
Neuropathic
Mixed
Psychogenic
Idiopathic/Putative/Dysfucntional

4. Five types of pain
•
•
•
•
•
Nociceptive
Neuropathic
Mixed
Psychogenic
Idiopathic/Putative

5. Nociceptive pain

6. Five types of pain
•
•
•
•
•
Nociceptive
Neuropathic
Mixed
Psychogenic
Idiopathic/Putative/Dysfucntional

7. Neuropathic pain
Neuropathic pain is pain arising as a direct consequence of a lesion or
disease affecting the somatosensory system
Treede et al., Neurology 2008

8. Clinical diagnosis
Peroneal
mononeuropathy
L5- radiculopathy
Saphenous
mononeuropathy
L3- radiculopathy
Brachial plexopathy
Polyneuropathy
Myelopathy
Amiotrophy
Herpes Zoster
Musculoskeletal pain

9. Five types of pain
•
•
•
•
•
Nociceptive
Neuropathic
Mixed
Psychogenic
Idiopathic/Putative/Dysfunctional

10. Che dolore hanno le persone con ED?
Può essere un dolore neuropatico?
Our preliminary findings are apparently in contrast with common sense, that is, in
EDS, pain is directly linked to primary joint damage and, consequently, is mainly
nociceptive in origin. In fact, our results suggest that pain is frequently neuropathic.
This implies that the pathophysiology of pain in EDS may be more complex than
expected, and that musculoskeletal involvement cannot explain the entire spectrum
of pain. Accordingly, it is likely that pain symptoms in EDS are the result of different
pain-triggering mechanisms.
Camerota et al., J Pain Symptom Manag 2010

11. Indagini strumentali
Quantitative Sensory Testing
(Aδ- and
C fibres mediated)
C-fibres
Aδ-fibres
Aβ-fibres
NCS (Aβ-fibre mediated)
Laser evoked potentials (Aδ-fibre mediated)

12. Questionari
DN4 Questionnaire
Fibromyalgia Rapid Screening Tool (FiRST)
Does my pain have one or more of the following
characteristics?
Items
1. Burning
Y
N
2. Painful cold
Y
N
3. Electric shocks
Y
N
Is the pain associated with one or more of the following
symptoms in the same area?
Y
N
5. Pins and needles
Y
N
6. Numbness
Y
N
7. Itching
Y
N
8. Hypoesthesia to touch
Y
N
9. Hypoesthesia to prick
Y
N
Is the pain located in an area where the physical
examination reveals one or more of the following?
In the painful area, can the pain caused or increased by
Y
My pain is accompanied by a continuous and very
unpleasant general fatigue
My pain feels like burns, electric shocks or cramps
4. Tingiling
10. Brushing
I have pain all over my body
N
My pain is accompanied by other unusual sensations
throughout my body, such as pins and needles, tingling
or numbness
My pain is accompanied by other health problems such
as digestive problems, urinary problems, headaches or
restless legs
My pain has a significant impact on my life, particularly
on my sleep and my ability to concentrate, making me
feel slower generally
Y/N

13. Risultati
In tutti i soggetti con sindrome di Ehlers Danlos studiati DN4, visita clinica neurologica, studio di
conduzione nervosa, dei potenziali evocati laser e delle soglie percettive termodolorifiche sono
risultati normali
Distribuzione topografica dolore
Fibromyalgia Rapid Screening Tool (FiRST)
Items
Y/N
(%)
I have pain all over my body
80
My pain is accompanied by a continuous and very
unpleasant general fatigue
90
My pain feels like burns, electric shocks or cramps
90
My pain is accompanied by other unusual sensations
throughout my body, such as pins and needles, tingling
or numbness
90
My pain is accompanied by other health problems such
as digestive problems, urinary problems, headaches or
restless legs
90
My pain has a significant impact on my life, particularly
on my sleep and my ability to concentrate, making me
feel slower generally
90

14. Discussione

15. Discussione
Infiammazione cronica
Persistente attivazione del sistema dolorifico
Sviluppo della sensitizzazione centrale

16. Functional connectivity of PAG in fibromyalgia
Controls
Patients
Controls > Patients