PainChampions

November 18, 2016

WHAT TYPES OF PAIN AFFECT THOSE WITH EHLERS-DANLOS? (PART ONE)

Ehlers-Danlos syndromes disrupt our bodies at the most fundamental levels, leading
to the possibility of widespread effects at varying levels of severity. These essential
problems can lead to the full range of possible pain types, any or all of which can result
from our having Ehlers-Danlos. Knowing which types of pain each of us has may
make treating our pain easier.

Generally, pain is either nociceptive (rising from stimulation of nerve cells) or

neuropathic (rising from problems with the nerves themselves).

But pain is more complicated than those two categories suggest, and most writing
about pain in Ehlers-Danlos include, in some form, the following1:

Musculoskeletal pain, related to soft tissue and joint injuries;

Bone-related problems such as osteoarthritis and osteoporosis;

Myofascial, rising from the connective tissue wrapped around our internal
structures to hold everything in place;

Headaches and head pain; and

Visceral pain from internal organs, including gastrointestinal, abdominal, and

urological sources.

When acute pain is untreated or managed incompletely, it can set us up for ongoing
chronic pain issues quite apart from the chronic-acute pain of daily injuries in Ehlers-
Danlos. For instance, chronic pain can be established by prolonged soft tissue/joint
pain, which can activate and increase the number of NMDA receptors, thereby passing
more pain signals to the brain.2

There are also complicating problems in many of us with Ehlers-Danlos, that often
work in a sort of feedback loop, both worsening pain and worsened by painfatigue,
sleep disorder, depression, anxiety. Not enough is known yet to explain why these
factors arise, but let me be clear: none of these cause Ehlers-Danlos syndromes.
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However, improving any or all of these co-morbid conditions can make living with
Ehlers-Danlos pain easier.

MUSCULOSKELETAL PAIN

This is most clearly associated with Ehlers-Danlos, starting with the joint pain many us
have, from the direct problems of full dislocations and partial dislocations or slipping
(subluxations).

It wasnt until the late 1990s and the subsequent decade-long NIA Studies of Heritable
Disorders of Connective Tissues that we really began to understand that pain is an
intrinsic feature of EDS. This was at least partly due to the unusual nature of Ehlers-
Danlos dislocationsnot all of us dislocate with pain, or with the evidently terrible agony
most people endure when they dislocatewhich may be why some doctors still hold to
the outdated and mistaken notion that Ehlers-Danlos dont cause pain.

Of course our joints dont move in isolation, theyre surrounded and supported by
soft tissue. Remember that the defect in our connective tissue interferes with the
structure that keeps our tissue from stretching too far. When a joint dislocates,
the tissue around that jointas well as whatever muscles, tendons, or fascia are
connected to that joint directly or indirectlyall is stretched beyond the ability of that
tissue to hold itself together. So it gets injured from a myriad of microscopic tears,
over and over and over, each time that joint slips, multiple times a day or even an hour.
Much of that damage happens in the fascia, the sheets of connective tissue that hold
our bodies together by keeping in place our muscles, blood vessels, nerves, organs
pain in our fascia means were literally encased in pain.

This is the chronic-acute pain that is inherently part of Ehlers-Danlos, and forms the
background for other musculoskeletal issues. A significant number of us develop
a fear of falling3 and of movement and re-injury4, both of which can worsen our
problems through loss of strength and support.

There are also bone-related issues in osteoarthritis and osteoporosis.

While there is some conflicting evidence as to whether Ehlers-Danlos lead to

osteoarthritis, to me common sense says there has to be a relationship. One of
the causes of osteoarthritis is commonly held to be wear-and-tear; the Arthritis
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Foundation says, Repetitive movements or injuries to joints (such as a fracture,

surgery or ligament tears) can lead to osteoarthritis. Some athletes, for example,
repeatedly damage joints, tendons and ligaments, which can speed cartilage
breakdown.An imbalance or weakness of the muscles supporting a joint can also lead
to altered movement and eventual cartilage breakdown in joints.5 It seems logical
to assume that the chronic-acute effects of ongoing dislocations would contribute
as well and a large percentage of those diagnosed with hypermobile Ehlers-Danlos
report early-onset osteoarthritis.

There is divergent discussion about how strongly and even if osteoporosis relates
to Ehlers-Danlos syndromes. Certainly osteoporosis is a definitive feature of
kyphoscoliotic EDS, arthrochalasia EDS, and the EDS/osteogenesis imperfecta
overlap.6 Howard Levy in his GeneReview article, Ehlers-Danlos Syndrome,
Hypermobility Type, says, There is very limited and contradictory evidence regarding
bone mineral density in EDS, hypermobility type. Dolan et al7 found bone density to
be reduced by up to 0.9 SD in patients with EDS compared to healthy controls, but
that study did not look specifically at patients with the hypermobility type of EDS.
Compared to age- and sex-matched controls, Gulbahar et al8 reported bone density
reduction of up to 0.5 SD among premenopausal women with joint hypermobility
syndrome (now considered identical to EDS, hypermobility type). However, Carbone et
al9 found no difference in bone density between women with EDS, hypermobility type
and normal controls after adjusting for height, weight, and physical activity.10

A survey by Marco Castori found that literature showed a strong association between
Ehlers-Danlos and generalized joint hypermobility with reduced bone mass density in
older children and adults, which matched with his personal experience.11

There is, however, literature which is more definite about effects. In 2015, a study
detailed that vertebral fractures were significantly more prevalent in Ehlers-Danlos
than in control participants (38.5% and 14.4% respectively, and not significantly
different between hypermobile and classical types). Severe back pain was a result of
vertebral fractures (no surprise, in my personal experience). The authors conclusion:
The occurrence of vertebral fractures in patients with normal or low-normal BMD
is consistent with the hypothesis that bone quality more than bone quantity may be
impaired in EDS.12
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Clearly more needs to be learned, but in the meantime, its safe to say that bone health
directly affects pain, and is in some way associated with EDS even if how is in question.

NEUROPATHIC PAIN

Neuropathy is a problem with the nerves themselves, rather than the stimulation
triggering the nerves. Neuropathies most often arise in the peripheral nerves rather
than the spine and brain (central nervous system). There are sensory nerves that
control sensation, motor nerves that allow power and movement, and autonomic
nerves (the nerves that control the systems of the body. Mononeuropathy describes
a single nerve being affected, and polyneuropathy describes the involvement of
multiple nerves.13

Neuropathic pain is a complex, chronic pain state that usually is accompanied by

tissue injury. With neuropathic pain, the nerve fibers themselves may be damaged,
dysfunctional, or injured. These damaged nerve fibers send incorrect signals to other
pain centers. The impact of nerve fiber injury includes a change in nerve function both
at the site of injury and areas around the injury.14

Neuropathic pain seems to accompany Ehlers-Danlos. The pain shows up as burning

sensations; aching or stabbing pain; even electric shock sensations going up or down
the legs and feet. These sensations come in a range, from unpleasant annoyances to
painful intrusions:15,16

Paresthesias, or abnormal sensations without an obvious physical cause such

as tingling, tickling, pricking, numbness or burning;

Numbness, or impaired sensation; and

Dysesthesias, or abnormal unpleasant sensations in reaction to being touched,

such as burning, wetness, itching, electric shock, and pins and needles.

One attempt to explain why this happens in Ehlers-Danlos is that nerves are being
compressed, perhaps by being trapped in joints as they move. But many of us have
neuropathic pain at rest, and in body-symmetrical patterns, which seems unlikely
to be the result of random compression in joints. Another explanation is that axons
themselves are damaged; this might be true for some of us, but has been said to be
rare in Ehlers-Danlos.17 However, there is an explanation for this which might imply
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axon damage is more common in Ehlers-Danlos than previously noted. Nerves are
surrounded by three layers of connective tissue, which may be as fragile as other
connective tissue in Ehlers-Danlos, and therefore unable to protect axons from
trauma when soft tissue is overstretched.18

Recent discoveries about small fiber neuropathy in Ehlers-Danlos19 may prove to be

very useful in understanding Ehlers-Danlos pain.

There are other causes of neuropathic pain that may apply to Ehlers-Danlos; one is
complex regional pain syndrome18, an amplified musculoskeletal pain syndrome that
often worsens over time. The cause of CRPS is unknown, but there are associations
with dysregulation of the central nervous and autonomic nervous systems, which can
be an effect of Ehlers-Danlos.

VISCERAL PAIN

Recurrent pain originating from internal organs is widely reported in Ehlers-Danlos.

Abdominal pain is most widely reported in adults and hypermobile type EDS.20,21 Why
isnt yet explained. It may be the increased ability of an organ to distort from applied
pressure in Ehlers-Danlos also increases sensitivity to pain in that organ.15 this might
be particularly true if abdominal ligaments are lax and in connection with organ
prolapse.22,23

Menstrual pain is common in Ehlers-Danlos, sometimes the result of other disorders,

but for most women, it remains unexplained.24 Pelvic prolapse is also common in
Ehlers-Danlos (particularly in hypermobile type), which clearly would contribute to
discomfort and pain.2527

Unusual chest pain is reported by many of us, too. There may be musculoskeletal
sources related to the rib cage and spine, as well as from the many connective
tissue functions allied with them. There may be cartilage inflammation, called
costochondritis. Chest pain may also be caused by postural orthostatic tachycardia
syndrome, which is a common complication in EDS.

CONCLUSIONS

Musculoskeletal pain is probably the most immediately recognizable form of pain

in Ehlers-Danlos syndromes, as a result of mechanical issues and resulting ongoing
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trauma. But research seems clear that neuropathic pain is just as likely, although not
yet explained; small fiber neuropathy may prove to be the main source. And there are
a variety of visceral pains including GI, gynecologic, and chest pains.

Next month will be an examination of headache and head pain as well as the
complications that affect our pain; then pain management suggestions will take the
focus.

Mark Martino, The Ehlers-Danlos Society

SOURCES
1
Castori (2016). Pain in Ehlers-Danlos syndromes: manifestations, therapeutic strategies and future
perspectives. Expert Opinion on Orphan Drugs, 4:11, 1145-1158, DOI:10.1080/21678707.2016.1238302
2
Niesters M, Martini C and Dahan A (2014). Ketamine for chronic pain: risks and benefits. Br J Clin
Pharmacol. 2014;77(2):357367.
3
Rombaut L, Malfait F, De Wandele I et al. (2011). Balance, gait, falls, and fear of falling in women with
the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken). 2011;63:14321439.
4
Celletti C, Castori M, La Torre G et al. (2013). Evaluation of kinesiophobia and its correlations with
pain and fatigue in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.
Biomed Res Int. 2013;2013:580460.
5
http://www.arthritis.org/about-arthritis/types/osteoarthritis/causes.php (accessed November 15,
2016).
6
Cabral WA, Makareeva E, Colige A et al. (2005). Mutations near amino end of 1(I) collagen cause
combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide
processing. Journal of Biological Chemistry, vol. 280, no. 19, pp. 1925919269, 2005.
7
Dolan AL, Arden NK, Grahame R and Spector TD (1998). Assessment of bone in Ehlers Danlos
syndrome by ultrasound and densitometry. Ann Rheum Dis. 1998;57:6303.
8
Gulbahar S, Sahin E, Baydar M, Bircan C, Kizil R, Manisali M, Akalin E and Peker O (2006).
Hypermobility syndrome increases the risk for low bone mass. Clin Rheumatol. 2006;25:5114.
9
Carbone L, Tylavsky FA, Bush AJ, Koo W, Orwoll E and Cheng S (2000). Bone density in Ehlers-
Danlos syndrome. Osteoporos Int. 2000;11:38892.
10
Levy HP (2016). Ehlers-Danlos Syndrome, Hypermobility Type. National Center for Biotechnology
Information GeneReviews, Pagon RA, Adam MP, Ardinger HH et al., editors. Seattle (WA): University
of Washington, Seattle; 1993-2016. https://www.ncbi.nlm.nih.gov/books/NBK1279/ (accessed
November 15, 2016).
11
Castori M (2015).Ehlers-Danlos syndrome(s) mimicking child abuse: Is there an impact on clinical
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practice? Am J Med Genet C Semin Med Genet. 2015 Dec;169(4):289-92. doi: 10.1002/ajmg.c.31460.
Epub 2015 Oct 9.
12
Mazziotti G, Dordoni C, Maffezzoni F, Galderist F et al. (2015). High Prevalence of Vertebral
Fractures in Patients with Ehlers-Danlos Syndrome. Endocrine Societys 97th Annual Meeting and
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SAT-225 (accessed November 15, 2016).
13
Webberley, H (2016). http://www.medicalnewstoday.com/articles/147963.php (accessed November
15, 2016).

Reviewed by Robinson, J (2015). Neuropathic Pain Management. http://www.webmd.com/pain-

14

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15
Castori M, Morlino S, Celletti C et al. (2013). Re-writing the natural history of pain and related
symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. Am J
Med Genet A. 2013;161A:29893004.
16
Castori M, Morlino S, Celletti C et al. (2012). Management of pain and fatigue in the joint
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Voermans NC, Knoop H and van Engelen BG (2011). High frequency of neuropathic pain in Ehlers-
17

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18
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Cazzato D, Castori M, Lombardi R et al. (2016). Small fiber neuropathy is a common feature of
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20
Zarate N, Farmer AD, Grahame R et al. (2010). Unexplained gastrointestinal symptoms and joint
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22
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24
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25
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