Somatosensory profile of pain in myotonic dystrophy type 2 and fibromyalgia

DM2 is a rare dominantly inherited multisystemic disorder with a heterogeneous
phenotype. In the Netherlands there are 54 known patients with DM2. The
clinical features of DM2 were first described in 1994 [Ricker et al 1994]. In
2001, the genetic defect of DM2 was identified as an unstable CCTG
tetranucleotide repeat expansion in the ZNF9 gene on chromosome 3q21.3 [Liquori
et al 2001]. The core symptoms of DM2 are proximal muscle weakness, muscle
pain, myotonia and cataracts [Day et al 2003]. Other characteristics are sleep
disturbances, fatigue, gastrointestinal symptoms and involvement of the heart,
endocrine and autoimmune system [Tieleman et al 2008, 2010; Wahbi et al 2009].

Pain is an important and early feature of DM2. According to Suokas et al, the
prevalence of pain in DM2 is 76% [Suokas et al 2012]. In up to a third of DM2
patients, pain is the most disabling feature [George 2004], and it tends to
increase with disease duration. 69% of DM2 patients with nocturnal sleep
disturbances report pain as the cause [Tieleman 2010]. DM2 patients with pain
show a lower quality of life compared to those without pain [Suokas et al
2012]. Moreover, according to Suokas et al both depressive symptoms and
insomnia occur significantly more frequently among DM2 patients with pain
compared to those without pain.

Several studies have tried to characterize the pain by means of questionnaires.
George et al reported that the spectrum of coexisting types of musculoskeletal
pain in DM2 is wide [George et al 2004]. They found that the pain is
widespread, most pronounced localised in thighs, back and proximal upper limbs.
Ricker et al reported the pain to be fluctuating, sometimes lasting for hours,
days or even weeks and then disappearing for days or weeks [Ricker et al 1995,
Ricker et al 1999]. Several studies reported that the pain is induced by cold
and reduced by warmth [Day 1999, George 2004, Suokas et al 2012]. Furthermore,
it seems to increase during and after exercise, and is relieved by rest [George
et al 2004; Suokas et al 2012]. A lot of patients report tenderness in the
muscles, aggravated by palpation [George et al 2004, Ricker et al 1995]. George
et al and Ricker et al did not find a relation between the severity of pain and
myotonia [George et al 2004, Ricker et al 1995]

There is no curative treatment for DM2, and the symptomatic effect of pain
medication has not widely been studied, only effects in a few cases have been
described. In single cases, a positive effect on pain is described in treatment
with NSAIDs, carbamazepine, phenytoin, a short-term course of corticosteroid
therapy, baclofen, tizanide and gabapentin [Ricker et al 1999, Meola et al
2000, Sander et al 1996, Udd et al 2006]. The pain and stiffness have been
improved in some patients after mexiletine [Day et al 1999; Moxley et al 2002].
However, mexiletine is not used extensively, because of concern about cardiac
arrhythmias. In conclusion, no consistently effective treatment is known for
pain in DM2.

A modern concept in treatment of pain is *mechanism based treatment* [Jensen et
al 2003]. In this concept not the underlying disease is target of treatment (as
many underlying diseases are unknown or not curable), but the mechanism that
causes the pain. Quantitative sensory testing
(QST) is a useful tool to quantify pain processing. It assesses different
aspects of pain. It examines the sensory pathway, from the function of
peripheral nerve fibers (large Ab fibers and small C fibers), the spinothalamic
pathways to the cortical regions in the brain [Rolke et al 2006]. Nociceptive
pain is caused by stimulation of peripheral nerve fibers that respond to
stimuli approaching or exceeding harmful intensity. It results in altered
sensory processing by the central nervous system. Ongoing nociceptive input
might lead to central sensitisation. However, in comes cases changes in central
pain processing are so pathological that central pain perception becomes
autonomous and thus independent of peripheral pain inputs [Buscher et al]. With
QST several pain thresholds are determined and a somatosensory profile is made.
Approximately, there are two main profiles: patients with normal central pain
processing and with disturbed central pain processing.

The Pain Treatment Center of UMC St. Radboud has a regional function for
regular treatment of pain and a supra-regional function for advice of complex
pain syndromes. Quantitative Sensory Testing (QST) is frequently performed,
both in daily practice as well as in scientific research, according to a
standardized protocol [Buscher et al 2005].

In conclusion, pain is common in DM2 and for up to a third of patients the most
disabling feature. The mechanism that causes pain in DM2 is unknown. So far, no
trials have been performed to investigate the effect of treatment in DM2. The
goal of this study is to characterize pain in DM2 more extensively, by
accomplishing quantitative sensory testing as well as questionnaires. We expect
this will lead to a better understanding of the pathophysiological nature of
pain in DM2, and eventually to a mechanism based treatment. Moreover, we will
also perform the same tests in fibromyalgia patients, to compare the results.
If similarities in the nature of pain in both patient groups are found,
treatment strategies of fibromyalgia might be used in DM2 as well.

1. What is the somatosensory profile of DM2 patients?

2. What are the similarities and differences between the somatosensory profile
of pain in myotonic dystrophy type 2 and fibromyalgia patients?

Observational study

The burden for the patient is fulfilling five questionnaires and one visit to
our outpatient department for QST testing. QST testing is harmless, although
some patients will find this test unpleasant. There is no immediate advantage
for the patient. However, if this study leads to a better understanding of the
pathophysiology of pain in DM2, we are closer to an adequate treatment of this
disabling feature of DM2.