Fernandes 1

Giselle Fernandes
Honors 222 C
9 June 2015

A Multidisciplinary Approach to Pain in Multiple Sclerosis

The power MS has over me is so strong, I start to believe Im chained to it and theres
no escapeThats when I cant see beyond the fog of the disease and I wonder if the pain will
ever let me go. - Nicole Lemelle, The Devil Inside: Living With MS
Introduction
Multiple sclerosis is a chronic, debilitating disease of the central nervous system that
currently has no cure. It is considered autoimmune and affects a staggering 2.5 million
individuals worldwide (Jawahar et. al, 2013). Demyelination, gliosis, and inflammation within
the central nervous system are thought to be the main causes of pain and disease progression in
multiple sclerosis and have serious effects on the quality of life in MS patients (Khan and
Pallant, 2007).
Multiple sclerosis can hardly be considered a recent disease. Its effects were described
as far back as the Middle Ages and it was chronicled as a clinical condition as early as the 17th
century (Joy and Johnston, 2001). Despite major advancements in our understanding of MS, the
mechanism of the disease and the role of pain in multiple sclerosis continue to perplex the
scientists and physicians alike.
A Holistic View of MS Pain
Historically, pain was not thought seen as a major feature of multiple sclerosis, but
through the years patients afflicted with MS have time and time again cited pain as the primary

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cause of their suffering (Lynch et. al, 2008). In the past, MS pain was typically viewed solely
through a biomedical lens (Madsenm et. al, 2012). Though this approach helped treat many
aspects of patients pain, it was later realized that a more holistic framework of treatment had the
potential to achieve much greater steps in the alleviation of MS pain.
Multiple sclerosis in its essence is a disease that involves both biomedical and
psychosocial aspects. Therefore, only with appreciation of both these types of factors can
scientists and the general public hope to gain insight into how the disease operates and what this
means for the lives of MS patients. This paper endeavors to explore a variety of the biomedical
and psychosocial components of multiple sclerosis so as to better understand the mystery of MS
pain and how we can make progress in alleviating the struggles of MS patients.
Pain in Multiple Sclerosis
Pain is the most commonly reported grievance of patients living with multiple sclerosis
(Jawahar et. al, 2013). In a research study conducted by OConnor et. al, MS patients reported
average pain levels ranging from 4.8-5.8 on a 0-10 scale. The research also revealed that MS
patients were more likely to have moderate to severe pain, use analgesics, and describe pain as
interfering with daily activities, in comparison to patients without the disease (OConnor et. al,
2008). Pain of clinical significance occurs in more than 50% of MS patients, with a prevalence as
high as 90% shown in many studies (Newland et. al, 2005). Despite the relatively high
occurrence of pain in multiple sclerosis, the issue has proven extremely difficult to address, in
part because of the complexity of MS pain. Though most MS patients do experience pain at some
point or another, pain incidence shows no apparent correlation to disease severity (Solaro et. al,
2003). The disease can also result in many different types of pain, and even in a single patient
these pains can vary widely throughout the course of the disease (Truini et. al. 2013).

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Additionally, MS patients often experience both chronic and acute pain and typically have
multiple pain sites throughout their bodies (Hadjimichael et. al, 2007). As a result of all these
complications, it is often very difficult for physicians to interpret the pain of MS patients and
offer effective treatments.
Mechanism of Pain in MS
Despite the many issues surrounding MS pain, much progress has been made in better
understanding the mechanism of pain in multiple sclerosis. Many researchers support the theory
that persistent pain in MS results from nerve injury that leads to the formation of lesions and
demyelination. This hypothesis is supported by the fact that abnormal sensory test results have
been found in patients with MS (OConnor et. al, 2008). These tests have shown MS patients to
often have cold allodynia and mechanical hyperplasia (Lynch et. al, 2008). On a biochemical
level, lesion formation and demyelination are thought to also result in alterations of sodium ion
channels or channel blockers in afferent fibers that disrupt the sensory pathway (Solaro et. al,
2003) (Richert et. al, 2010). As a result of this disruption to the spinothalamocortical pathway,
the brain may not receive the messages it was intended to, leading to numbness, or may
misinterpret the messages, leading to burning, tingling, or persistent pain. Other studies have
focused on the role of satellite glial cells (SGCs) in mouse models with a disease very similar to
MS. The results of these studies have found that SGCs in the dorsal root ganglia are activated in
subjects with the disease and reveal that coupling of SGCs has been shown to be positively
correlated with increased pain levels (Warwick et. al, 2014).
Though there is quite a variety of postulations about the mechanism of MS pain, it is
important to remember that the pain from multiple sclerosis may very likely denote etiologic
heterogeneity (Aicher et. al, 2004). Most research on MS pain has come to the conclusion that

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injury in either A or C fibers can very well lead directly or indirectly to sensations of pain and
numbness (Nauen et. al, 2012). This means that different MS patients could quite possibly
experience pain due to very different mechanisms. Furthermore, individual MS patients could
likely experience pain from diverse mechanisms at different stages of the disease. Awareness of
all these complexities is vital for both physicians and researchers working to better understand
the mechanistic aspects of the disease.
Acute Pain in MS
Acute pain is often seen as the initial warning sign for individuals soon to be diagnosed
with multiple sclerosis. These types of pain are of detected very early on in the disease
progression and can vary widely from patient to patient. Acute pain can result from actual cell
damage from demyelination and gliosis or can signify that damage has already occurred (Nauen
et. al, 2012).
One of the first types of pain experienced by multiple sclerosis patients is trigeminal
neuralgia. This is a stabbing pain felt in the facial region, which, though powerful, can usually be
treated effectively with medications (Pain and MS: the Basic Facts. 2004).
Patients in whom the disease has progressed further may also experience Lhermittes sign
and the MS hug. Lhermittes sign is a brief, powerful electric shock-like pain that originates in
the back of the head and travels down the spine when the individual attempts to bend forward.
Often, patients may wear a soft collar to limit such movement, and medications can also be used
to treat such pain (Pain and MS: the Basic Facts. 2004). The MS hug is a burning, aching,
girdling around the body which is thought to be a dysesthesia. This type of pain can be treated in
a variety of ways, including anti-depressant medications, pressure stockings or gloves to convert

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the pain into a sensation of pressure, and warm compresses that can transform the pain into a
sensation of heat (Pain and MS: the Basic Facts. 2004).
Patients may also experience either central neuropathic pain. Continuous central
neuropathic pain in MS is believed to be a result of axonal damage and demyelination that leads
to hyperexcitability in the nervous system. Intermittent central neuropathic pain, on the other
hand, is thought to be a result of ectopic impulses in already damaged neurons and the
communication of such sensation to undamaged neurons due to emphaptic coupling (OConnor
et. al, 2008).
Chronic Pain in MS
In multiple sclerosis, chronic pain is believed to often be a result of specific damage of
glial cells in the brain (Aicher et. al, 2004). These types of pains are usually felt in through
sensations of pins-and-needles, burning, or prickling. Patients may also experience flexor spasms
in the form of muscle cramps or spasms. These can be treated via anti-inflammatory agents,
stretching and exercising, heat therapies, massage and physical therapy, and by carefully
balancing sodium and water intake so as to better regulate ion channels. MS patients often also
mention back pain, pain in the extremities, and headaches (OConnor et. al, 2008). In multiple
sclerosis, headache pain especially is seen as resulting from a complicated mix of inflammatory,
neuropathic, and musculoskeletal mechanisms that makes treatment of the pain all the more
difficult (OConnor et. al, 2008).
Difficulties in Treating MS Pain
As a result of both the complex nature of the disease and the vast variety of pains that it
can lead to, many challenges arise in the treatment of MS pain (Joy et. al, 2001). The pain
experienced by MS patients is often regarded as mixed pain, different types of pain that are

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difficult to quantify distinctly they arise from differing pathophysiological mechanisms (Truini
et. al, 2013). Since MS patients may experience multiple types of pain simultaneously, teasing
apart chronic and acute pain can also be a particular difficulty. In addition, some of the pains MS
patients face, most notably headaches and back pain, are so common in the general population
that it is difficult to determine whether the pain is actually caused by the disease (Joy et. al,
2001). Furthermore, there is some concern that certain medications used to treat the disease may
actually exacerbate the pain experienced by patients, stirring the ethical debate about whether the
primary goal of health care should be to treat medical conditions or alleviate suffering (Joy et. al,
2001).
Experimental Research
A great deal of experimental studies have been conducted in animal models in an attempt
to better understand multiple sclerosis and the role of pain in the disease. In many rodent studies,
a disease that is extremely similar to MS called experimental autoimmune encephalomyelitis
(EAE) has been used to examine the effects of the disease on pain in model organisms. EAE
simulates many of the characteristic and biochemical features of MS, such as demyelination and
inflammation in the central nervous system (Aicher et. al, 2004). Experiments using mouse
models have broken ground in our understanding of MS, from the potential mechanistic role of
satellite glial cells to the effects the disease has on sensory, motor, and cognitive deficits
(Warwick et. al, 2014) (Khan et. al, 2014). Research using EAE animal models show great
promise in advancing our understanding of multiple sclerosis and pain.
Imaging Studies
Imaging studies have also been utilized to better interpret multiple sclerosis and the pain
associated with the disease, though the main theme seems to be that correlation, even when it

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exists, does not necessarily mean causation. In one study, MS patients who chose to have an MRI
were found to have between 5-16 lesions in the brain and a third of the patients also had lesions
in medial and lateral thalamic regions (OConnor et. al, 2008). Yet these results were so common
in patients with multiple sclerosis that no substantial relation to pain could be found, despite
pathological evidence of cell damage. In a study focusing on central pain in MS, no association
at all was found between the site of demyelination and the related pain (Svendsen et. al, 2011). In
more somewhat more promising study honing in particularly on Lhermittes sign, patients
experiencing such pain were found to be much more likely to also have lesions in the spinal cord
(OConnor et. al, 2008). Overall, results from imaging studies must be interpreted very carefully
so as to avoid hasty conclusions. Most importantly, researchers and physicians must remember
that physical signs of pain may not show up altogether. The patients word must remain the
primary and ultimate source of information regarding his or her pain, no matter how advanced
our technological abilities become.
Current Treatments for MS Pain
There is quite a variety of pain treatment options for patients and physicians deciding on
a management plan for multiple sclerosis. In the initial stages of MS, the main goal is typically to
treat the disease itself with disease modifying therapy. This involves use of interferon- to
balance inflammatory agents and slow the progression of the disease to counter the advancement
of disability (Crayton et. al, 2006). Unfortunately, some sources fear that disease modifying
treatment can actually contribute to increases in pain for many MS patients.
Relapse Treatments
Relapse treatment usually focuses on reducing inflammation through the use of
corticosteroids that can relieve numbness and tingling (Joy et. al, 2001). Other relapse

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medications can include anti-seizure or anti-spasticity medications and narcotics or opiates for
tissue-related damage. Antidepressants and SSRIs, when prescribed at a lower dose than used
for treating depression, have shown promise in relieving MS pain by modifying how the brain
perceives sensations of pain (Nauen et. al, 2012). In recent years, there has also been some
success in using certain cannabinoids to relieve pain, spasticity, and anxiety in MS patients.
Unfortunately, there is also concern that genetic and environmental factors could mean that some
patients may be predisposed to developing problematic side effects such as psychosis or
schizophrenia (OConnor et. al, 2008). Current regulations on cannabinoid research has made it
extremely difficult for researchers to undertake controlled trials to see if such concerns are truly
justifiable.
Alternative Therapies
Alternative therapies have also shown promise in relieving pain and increasing function
for MS patients. This may include simple lifestyle changes such as wearing loose clothing or
pressure stockings and gloves or using warm compresses to alter the sensation of pain. Patients
may also find pain relief by taking supplementary vitamin B in cases where the disease may be
involved with vitamin B deficiency or applying topical ointments such as capsaicin cream, which
stimulates and then decreases the intensity of pain (Nauen et. al, 2012). Physical therapy and
exercise have also shown to be extremely effective in alleviating musculoskeletal pain associated
with MS (Joy et. al, 2001). Some providers also recommend using a process coined gating
which involves keeping busy with other activities so as to allow the brain to modify what
information it takes in (Nauen et. al, 2012). Through a similar process, meditation has also been
useful in keeping the brain from focusing solely on pain. Most importantly, physicians and

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providers of alternative therapies alike have agreed that a positive attitude and an active lifestyle
serve as the best medications of all (Pain and MS: the Basic Facts, 2004).
A Multidisciplinary Therapeutic Approach
Perhaps because a solid definition of the mechanism of MS pain is lacking, there is also
dearth of substantial guidelines for therapeutic approaches (Solaro et. al, 2003). In recent years,
the use of multidisciplinary pain clinics have become more and more popular for treating MS
pain. This may include biofeedback, hypnosis, yoga, meditation, acupuncture, cognitive
behavioral therapy, and hypnosis (Pain and MS: the Basic Facts, 2004). Providers have found
such an approach useful in that it allows patients to use a multitude of treatment options. Because
MS pain is so often a result of a variety of mechanisms, and can change so drastically from
patient to patient, it only makes sense that a wide variety of treatment options be easily
accessible to patients as well.
The Patient-Physician Relationship:
Time and time again, the importance of communication has been cited by physician as a
major factor in alleviating MS pain (Pain and MS: the Basic Facts. 2004). Because MS pain
can vary so immensely, it is vital that patients clearly communicate what they are feeling to their
providers. Good communication will allow the patient and physician to work together to decide
on the best course of treatment (Nauen et. al, 2012). Providers can also make sure that patients
prior beliefs about pain do not negatively affect the results of their treatments (Osborne et. al,
2007). With clear communication, physicians can ensure that patients attain a full, realistic
understanding of pain that does not contribute to unnecessary fear.
Living with MS

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For patients living with multiple sclerosis, many lifestyle adjustments must be made to
cope with the effects the disease has on individuals lives. Often, these changes are difficult to
deal with and can cause as much stress as the disease itself. Most patients must alter their diets,
exercise differently and more frequently, and find ways to incorporate stress management in their
lives. Patients must also cope with decreased functionality without becoming frustrated or
embittered. For individuals, especially young adults, who do not expect to be making such major
lifestyle changes at that stage of their lives, these alterations can come as quite a shock.
Demographic Distributions
If multiple sclerosis was not already a mystifying disease, its distribution in populations
alone would categorize it amongst some of the most baffling conditions. Furthermore, the
incidence of pain in MS follows this bewildering pattern of distribution, with MS pain
demonstrating much higher prevalence in certain groups over others. Overall, multiple sclerosis
is far more common in females than in males, and even when such gender differences are
corrected for in pain studies, more women than men report having MS pain (Joy et. al, 2001).
Women and older patients have also been shown to have a longer duration of the disease and a
greater disconnect between incidence and severity of their pain than any other groups in the
population (Joy et. al, 2001). To date, researchers have been unable to find any solid biological
or social reasons for why such unusual distributions occur.
MS and Functionality
In about half the patients with MS pain, moderate to severe interference with regular
function has been reported (OConnor et. al, 2008). Overall, multiple sclerosis is the third most
common cause of disability for adults of 18-50 years of age and can lead to sensory, motor, and
cognitive problems (Khan and Pallant, 2007). Patients who reported having MS pain were also

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found to have a statistically higher levels of disability and found the disease to be significantly
more intrusive in their lives (Crayton et. al, 2006). Since the onset of the disease can come as
early as 20-40 years of age, such reductions in functionality can be particularly difficult to adjust
to (Newland et. al, 2005). For many patients, MS pain correlated with decreases in function leads
to giving up careers and essentially taking on a whole new life. Approximately one in four
patients with multiple sclerosis end up needing long-term care facilities, and in comparison with
other individuals using such services, individuals with MS demonstrate a higher prevalence of
pain and depression despite being an average of 20 years younger than patients without the
disease (Newland et. al, 2005).
MS, Pain, and Pregnancy
Because MS affects young women disproportionately, the disease also plays a
disproportionately large role in the lives of women hoping to have children. Coupled with the
debate of whether to focus on treating the disease or treating the pain that results from disease,
the issue of pregnancy with multiple sclerosis becomes increasingly more complicated. Because
so little is known about the drug safety of MS medications during childbirth, patients are actually
recommended to either suspend treatment or critically assess their plans to have children
(Weber-Schoendorfer et. al, 2009). Such decisions can have seriously detrimental physical and
psychological effects on the mother, child, or both. For women at various stages of planning
pregnancies, the psychological impacts of such factors can be varyingly traumatic.
Psychosocial Effects
The psychosocial effects of disease progression as well as pain treatment in multiple
sclerosis are astounding. Though MS is an undoubtedly debilitating disease, the quality of a
patients life is not solely determined by physical disability, but also by factors such his or her

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living area, social and spiritual life, education, employment, and attitude (Yamout et. al, 2013).
In terms of pain, psychosocial factors were shown to have a significant contribution to patients
reports of pain intensity and duration (Richert et. al, 2010). Though there are many aspects of
MS that are completely out the patients control, knowing that there is still so much he or she can
change may hopefully offer some optimism. Despite the obvious benefits of having social
interactions while living with MS, the disease itself can actually take quite a toll on ones social
life. Because of its neurological origins, MS is seen as an invisible disease, making the disease
itself and the pain associated especially difficult to explain to other people (Lemelle 2014). Even
close family and friends may not know how to appropriately respond upon finding out that an
individual is suffering from MS, and this can result in feelings of social isolation (Ambler et. al,
1999). Nevertheless, MS patients who are able to combat these difficulties, all the while
maintaining a positive attitude, are capable of reducing the deleterious impacts of the MS and
MS pain enormously.
Conclusion
-future studies, more research

Works Cited
Truini, A., et. al. A Mechanism-based Classification of Pain in Multiple Sclerosis. J Neurol,
Vol. 260. (2013): 351-367. Web. 25 May 2015.
Jawahar, Rachel, et. al. A Systematic Review of Pharmacological Pain Management. Drugs,
Springer Science & Business Media, Vol. 73. (2013): 1711-1722. Web. 25 May 2015.

Fernandes 13
Lynch, Jessica L., et. al. Analysis of Nociception, Sex, and Peripheral Nerve Innervation in the
TMEV Animal Model of Multiple Sclerosis. Pain, Vol. 136. (2008): 293-304. Web. 25
May 2015.
Khan, Fary and Julie Pallant. Chronic Pain in Multiple Sclerosis: Prevalence, Characteristics,
and Impact on Quality of Life in an Australian Community Cohort. The Journal of Pain,
Vol. 8.8. (2007): 614-623. Web. 25 May 2015.
Khan, Nemat, et. al. Establishment and Characterization of an Optimized Mouse Model of
Multiple Sclerosis-Induced Neuropathic Pain Using Behavioral, Pharmacologic,
Histologic, and Immunohistochemical Methods. Pharmacology, Biochemistry, and
Behavior, Vol. 126. (2014): 13-27. Web. 25 May 2015.
Aicher, Sue A., et. al. Hyperalgesia in an Animal Model of Multiple Sclerosis. The Journal of
Pain, Vol. 110. (2004): 560-570. Web. 25 May 2015.
Newland, Pamela K. et. al. Impact of Pain on Outcomes in Long-term Care Residents with and
without Multiple Sclerosis. J. Am. Geriatric Society, Vol. 53. (2005): 1490-1496. Web.
25 May 2015.
Crayton, Heidi J., et. al. Managing the Symptoms of Multiple Sclerosis: A Multimodal
Approach. Clinical Therapeutics, Vol. 28.4. (2006): 445-460. Web. 25 May 2015.
Svendsen, Kristina B., et. al. MRI of the Central Nervous System in MS Patients with and
without Pain. European Journal of Pain, Vol. 15. (2011): 395-401. Web. 25 May 2015.
Weber-Schoendorfer, C. and Schaefer, C. Multiple Sclerosis, Immunodulators, and Pregnancy
Outcome: A Prospective Observational Study. Multiple Sclerosis, Vol. 15. (2009): 10371042. Web. 25 May 2015.

Fernandes 14
Armon, Galit, et. al. Elevated Burnout Predicts the Onset of Musculoskeletal Pain among
Apparently Healthy Employees. Journal of Occupational Health Psychology, Vol. 15.4.
(2010): 399-408. Web. 25 May 2015.
Hadjimichael, Olympia, et. al. Persistent Pain and Uncomfortable Sensations in Persons with
Multiple Sclerosis. The Journal of Pain, Vol. 127. (2007): 35-41. Web. 25 May 2015.
Yamout, B., et. al. Predictors of Quality of Life among Multiple Sclerosis Patients: A
Comprehensive Analysis. European Journal of Neurology, Vol. 20. (2013): 756-764.
Web. 25 May 2015.
Osborne, Travis L., et. al. Psychosocial Factors Associated with Pain Intensity, Pain-Related
Interference, and Psychological Functioning in Persons with Multiple Sclerosis and
Pain. The Journal of Pain, Vol. 127. (2007): 52-62. Web. 25 May 2015.
Warwick, Rebekah, et. al. Satellite Glial Cells in Dorsal Root Ganglia are Activated in
Experimental Autoimmune Encephalomyelitis. Neuroscience Letters, Vol. 569. (2014):
59-62. Web. 25 May 2015.
Madsenm C.S., et. al. The Effect of Nerve Compression and Capsaicin on Contact Heat-Evoked
Potentials Related to A- and C-Fibers. Neuroscience, Vol. 223. (2012): 92-101. Web. 25
May 2015.
Ambler, Beth R. Let Me Tell You About Leaving the Express Lane. Inside MS. (1999): 60-61.
Print.
Pain and MS: the Basic Facts. Paraplegia News, Vol. 58.4 (2004): 50-51. Print.
Solaro, C., et. al. Pain and MS. The International MS Journal, Vol. 10. (2003): 14-19. Web. 25
May 2015.

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OConnor, Alec B., et. al. Pain Associated with Multiple Sclerosis: Systematic Review and
Proposed Classification. The Journal of Pain, Vol. 137. (2008): 96-111. Web. 25 May
2015.
Joy, Janet E. and Johnston, Richard B. Multiple Sclerosis: Current Status and Strategies for the
Future. Washington D.C.: National Academy Press, 2001. Print.
Nauen, Elinor. The Nerve Dance: Numbness and Tingling. Momentum: Healthy Living, Vol.
5.2. (2012): 30-33. Print.
Richert, John. Targeting MS Pain. Momentum: Research Now, Vol. 3.3. (2010): 66-67. Print.
Lemelle, Nicole. Living with MS: The Devil Inside. Healthline. 3 November 2014. Web. 26
May 2015.