Wednesday, November 30, 2022
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What Does Parkinson’s Pain Feel Like



The 2016 Edition Of The Researchers Days Organised By The Fnr Attracted A Large Audience That Took Part In Fascinating Scientific Experiments And Had The Opportunity To Mingle With The Present Researchers The Luxembourg Parkinson Study Was Of Course There Too With A Booth Called What Parkinsons Disease Feels Like We Took A Closer Look

Parkinson’s disease warning: Does your mouth feel like ...

In order to see how Parkinson’s disease feels like, hundreds of visitors tried on a Parkinson suit which simulates the two most representative motor symptoms of Parkinson’s disease: the muscle rigidity and the tremors. At first glance, the suit looks like a race car driver’s outfit. But together with the elbow and knee bands, and the ankle, wrist and chest weights, this suit shows how rigid the muscles and articulations can be, and how difficult it is for Parkinson’s disease patients to move.

All Up A Multidisciplinary Team Approach For Pain Management May Be Necessary In Addition To Your Movement Disorder Specialist Providers May Include Physical Or Occupational Therapists Psychiatrists And Even Pain Management Experts Each Of These Practitioners Targets A Different Aspect Of The Pain

Exercise to Relieve your Pain

Many different types of exercise can be beneficial for people with Parkinson’s disease , including non-contact boxing, tai chi, dancing and cycling, as some examples. If you have limited mobility, you can try chair yoga or other seated exercises. Whichever exercise you choose, make sure it is something safe and enjoyable so that you can stick with it.

It’s important to pace yourself and know your personal limitations. If during or after exercise you experience extreme pain you should look at modifying your routine and choose a less intensive exercise. Even the simplest exercise, including walking your dog or just puttering around the house or garden, can help alleviate symptoms of pain.

Cycling

If you need help or advise consult with a physical or occupational therapist to help design a personalised program for you. Learn more about exercise and Parkinson’s.

Non-pharmacological pain treatments

Complementary therapies are treatments used alongside conventional medicine. They take a more holistic approach than conventional medicine, aiming to treat the whole person including mind, body and spirit, rather than just the symptoms. These include massage therapy, mindfulness and meditation techniques, acupuncture, and heat or cold application. These may be used on their own or in combination with medication.

Anti Inflammatories

The Parkinsons Disease News Today Forums Are A Place To Connect With Other Patients Share Tips And Talk About The Latest Research Check Them Out Today

PD pain can resemble pain from other disease processes, especially as the patient ages and faces a multitude of other pain-causing conditions such as arthritis, spine degeneration, poor muscular conditioning, and such. In my case, PD pain is distinguished by the following:

  • The progression of body pain correlated with the progression of the disease over time.
  • Levodopa, a dopaminergic therapy, successfully reduces the pain.
  • The pain is worse during “off” periods.

My PD pain also has a particular characteristic: stinging , irritating tingling, burning, and muscle heaviness with increased pain on movement. This pain happens over large regions of the body and varies in severity. At its worst, it can last several days and reach level 7, inducing spontaneous tears.

PD with episodic chronic pain is disabling in several ways. First, high levels of pain obstruct clear thinking. Second, high levels of pain induce the fight-or-flight response, which interferes with emotion management. Third, the amount of energy necessary to manage it is very tiring . Chronic PD pain entails much more than body symptoms.

I have been a “communicator” most of my life, but it remains a struggle to find words that describe the unique character of PD pain. If you experience PD pain, please share your descriptors in the comments. Together we may find a common dialogue that will help others.

***

Im In Pain But I Dont Want To Take Carbidopa/levodopa Yet Because My Doctor Says It Will Only Work For Five Years Any Advice

It is true that as time passes and your disease progresses, you will have to take higher doses to replace the dopamine your body can no longer produce. However, the rate of dopamine loss is different for everyone. What your doctor may be telling you is that after taking carbidopa/levodopa for some time, you may begin to experience side effects like dyskinesia. It is important to understand that while you may experience this unwanted side effect, for example, you still benefit from the carbidopa/levodopa. If you believe your pain is Parkinson’s-related, and you have already tried other medications and complementary therapies without relief, it is probably time to try carbidopa/levodopa.

Negative Impact Of Severity Of Pain On Mood Social Life And General Activity In Parkinson’s Disease

Finally We Can See What Neuropathy Feels Like

This case control study designed for clinicians and rehabilitation specialists to effectively identify pain from the patient’s point of view determined that PD patients had significantly higher pain severity scores compared to controls. PD patients with depressive symptoms had significantly higher pain severity and pain interference scores than controls without depressive symptoms. PD patients reported greater scores on Global BPI pain interference and all components of the pain interference subscale. Therefore, PD and depression seem to be correlated with higher perceived pain, severity and interference. A report on this study, by Jose Marques Lopes, PhD., was published in Parkinson’s News Today, September 21, 2018.

Revisiting Pain In Pdthe 50 Shades Of Pain Experienced By Parkinsons Patients

Pain is a quality of life issue for people with Parkinson’s disease and can be under treated by doctors who may assume that is worsens as the disease progresses, although for some pain is an initial symptom of PD.  This article helps focus your physician’s attention in the right direction to accurately diagnose your pain.

Pain Management In Patients With Parkinsons Disease: Challenges And Solutions

This review focuses on the diagnosis and management of Parkinson-related pain.  It reviews the incidence and prevalence of PD, general pain and PD-related pain, the pathophysiological pathways of pain in PD, physiological pathways of pain relief, measurements of pain, clinical diagnosis of PD-related pain, and treatment strategies.

Q Are There Any Alternative Therapies That Are Effective For Pain In Pd

Dr. Fleisher: Although alternative therapies may be helpful, there is little evidence-based research to support their use. Certainly massage therapy, anecdotally, seems to be helpful for managing pain. Small studies suggest that acupuncture might improve sleep in patients with PD, but data on the effects on pain in PD is lacking. Larger, more well-controlled and reproducible studies of these therapies are needed.

Patients frequently ask about the effects of medical marijuana in managing PD, including pain symptoms. Several studies have looked at efficacy of marijuana in PD and have found that it probably is ineffective for most PD symptoms.11 However, we just don’t have enough evidence to know for sure. The most rigorous study of medical marijuana in PD showed a trend toward worsening tremor.11,12

For most people, stress and anxiety worsen tremor, and anything that relieves anxiety will improve tremor. Thus, modalities such as yoga, meditation, and mindfulness training will improve tremor. Similarly, medical marijuana may improve tremor in certain people by temporarily reducing anxiety and stress, but the evidence has not borne this out yet.

Q What Is The Pain Experience In Pd And Does It Differ Between Genders

Parkinson’s disease warning: Does your mouth feel like ...

Dr. Fleisher: As with almost everything else in PD, the pain experience is highly individualized, and no 2 people, regardless of gender, will have the same symptoms. Female gender appears to be an independent risk factor for chronic pain in PD, even though PD is more common in men than in women.2 Pain intensity also is higher in women than in men with PD.1

There is a lot of interesting research examining the contributions of hormones to the greater prevalence of PD in men or, conversely, the lower prevalence in women.3 Once we better understand the roles of sex hormones in the pathophysiology of PD, we may better understand whether hormones also play a role in the higher incidence of chronic pain in women with PD.

Q Are There Any Gender Disparities In The Treatment Of Pain In Pd

Dr. Fleisher: I don’t think there is any literature demonstrating gender disparities in pain treatment among patients with PD, but we do know that there are certainly gender disparities overall in the treatment of women with PD, so it would not be surprising to learn that women with PD-related pain are at a disadvantage and not getting the appropriate care that they need.

Pain Is An Unfortunately Common Problem In Parkinsons Disease

Of course, pain is common in the general population, especially among older people. A recent American study found that pain affected about twice as many people with Parkinson’s Disease than those of the same age and gender without PD. About 50% of Parkinson’s Disease patients in that study suffered from painful disorders. Men and women seem to be about equally affected. A very well described scenario is the patient who is followed for a painful frozen shoulder for a year or so before a tremor develops leading to a diagnosis of PD. Pain clearly plays a major role in quality of life. Everyone with chronic pain enjoys life less, leading to a vicious cycle in which pain causes depression or isolation which in turn leads to more pain.

Parkinson patients suffer from the same pain problems that other people have, often amplified by the motor dysfunction, but they also have additional pain problems which are unique to PD.

One recent review classified the types of pain Parkinson’s Disease patients have into: musculoskeletal, in which the pain results from problems with the muscles , bones or joints; dystonic, which is due to abnormal muscle contractions caused by the Parkinson’s Disease or the medications used to treat it; radicular pain, which is feels like the pain caused by pinched nerves; central pain, which is presumed due to abnormalities in the brain, and is a continuously present pain that cannot be explained otherwise; and discomfort related to an unpleasant urge to move.

Pain Is A Common But Overlooked Problem In Parkinsons Disease

Pain is an often overlooked non-motor symptom of Parkinson’s disease . Studies show that between 40-80% of people with PD report pain, which is likely why it is often suggested as a topic for this blog.

One of the reasons why the topic of pain and PD is difficult to address is that it is sometimes tough to discern whether a particular pain is due to PD or not. Chronic pain is such a common symptom among the general population, and people with PD are not immune to common problems as well. However, there are aspects of PD that may exacerbate the pain experienced from a common problem. In addition, there are particular types of pain that may be unique to people with PD.

Q What Is The Role Of Depression In The Pain Experience In Pd

What does sacroiliac joint pain feel like?

Dr. Fleisher: Depression is one of the most overlooked symptoms of PD, and it can affect over 30% of people with the disease at some point in their illness.5 I think there is a misconception that depression results from an adjustment disorder following diagnosis. While that may be partially true, patients with PD have alterations in various neurotransmitters—including serotonin and norepinephrine in addition to dopamine—that predispose them to depression.6,7

Depression is the primary factor related to quality of life in PD and is an independent risk factor for medication nonadherence. A physician could prescribe the most comprehensive regimen to control Parkinson’s symptoms, including pain, but if depression symptoms are not being addressed simultaneously, the likelihood that that person is going to take that regimen is pretty minimal.

Given the link between depression and chronic pain, patients who are depressed should be screened for chronic pain and vice versa. In my practice, we screen every patient with the Unified Parkinson’s Disease rating scale , which has both a patient-reported subjective component that includes questions about depression, pain, and altered sensation, as well as an objective component that includes a physical examination and questions about potential medication adverse effects . The patient fills out the subjective component every single time they come to the office.

What Lifestyle Changes Can I Make To Ease Parkinsons Symptoms

Exercise: Exercise helps improve muscle strength, balance, coordination, flexibility, and tremor. It is also strongly believed to improve memory, thinking and reduce the risk of falls and decrease anxiety and depression. One study in persons with Parkinson’s disease showed that 2.5 hours of exercise per week resulted in improved ability to move and a slower decline in quality of life compared to those who didn’t exercise or didn’t start until later in the course of their disease. Some exercises to consider include strengthening or resistance training, stretching exercises or aerobics . All types of exercise are helpful.

Eat a healthy, balanced diet: This is not only good for your general health but can ease some of the non-movement related symptoms of Parkinson’s, such as constipation. Eating foods high in fiber in particular can relieve constipation. The Mediterranean diet is one example of a healthy diet.

Preventing falls and maintaining balance: Falls are a frequent complication of Parkinson’s. While you can do many things to reduce your risk of falling, the two most important are: 1) to work with your doctor to ensure that your treatments — whether medicines or deep brain stimulation — are optimal; and 2) to consult with a physical therapist who can assess your walking and balance. The physical therapist is the expert when it comes to recommending assistive devices or exercise to improve safety and preventing falls.

Improve the quality of your sleep.

Opening The Medicine Box In The Mind: The Psychology Of Pain

In this 50-minute lecture, Beth Darnall, PhD explains how our experience of pain goes beyond the physical sensation of pain.  It has emotional and psychological components that affect our ability to treat pain.  She cites research to demonstrate that and shares 13 specific tips to reduce the experience of pain and increase treatment effectiveness.  Audience questions follow the lecture.

Q Is There Anything Else You Would Like To Tell Our Readers

Dr. Fleisher:There are so many symptoms of PD that it can be easy to overlook pain symptoms if a patient doesn’t report them. Remember that pain may be a really prominent symptom for patients, but, given that we have only learned how pain is connected to PD in the past 20 years, patients may not be aware of the association and may not bring up pain symptoms with their neurologist.

Thus, the burden is on us to ask about pain, particularly if the patient is depressed. If a patient with PD has both pain and depression, both of those comorbidities should be targeted, because it can be hard to achieve successful outcomes for either pain or depression if one is treated without the other.

The Overlaps Between Stress And Parkinson’s Disease Part 2

Pin on Chronic Illness

These changes in internal pressure under stress would also explain the feelings of heaviness/being crushed expressed above, since if the internal pressure forces in the body aren’t sufficient to overcome the external force of gravity, it would stand to reason that the body would start to adopt concave shapes, like the classic stooped posture of PD. This is easy to understand with a simple analogy of a balloon. If we pump up the balloon to a high pressure, the balloon would be perfectly round. However, if we then started to deflate it again, decreasing its internal pressure, then the sphere would begin to collapse under gravity: the balloon becomes more rugby ball or american football shaped. This is because the internal pressure pushing outwards is no longer sufficient to completely overcome the external force of gravity. As we keep deflating the balloon , the balloon will continue to flatten out on. Indeed, eventually it will be just be a flat pancake of rubber on the floor, of course.

Q Which Pharmacotherapies Are Best For Treating Pain In Pd

Dr. Fleisher: The first step is to make sure that Parkinson’s medications are optimized. For example, dystonic or musculoskeletal pain may be caused by Parkinson’s motor symptoms when dopamine levels are too low. If the patient is able to keep a pain diary, it may show a clear pattern of pain occurring the hour before each dose or before specific doses, suggesting the need to either increase the dosage preceding the pain episode, increase the frequency of medication dosing, or use adjunctive dopaminergic therapies to achieve more steady dopamine levels throughout the day.

In addition, optimal management of comorbidities that may contribute to pain is needed. The choice of pain medication depends on the pain type.

The first lines of treatment for musculoskeletal pain can be heat and cold packs and nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen.  

For dystonic pain, adjustment of dopaminergic medications is particularly critical; however, if dystonia consistently occurs in 1 particular body part, botulinum toxin injections also can be helpful. The goal of botulinum toxin injection is to weaken the muscle enough to stop the abnormal contractions and twisting, but the patient may lose function in the body part as a result . Thus, patient counseling is important to manage expectations.

Lower Back Pain And Back Of The Neck Pain Are Most Common

Pain occurs for a number of reasons and it’s not always clear what the cause is, making it difficult to figure out how best to treat it. I believe that most common pain problems in Parkinson’s Disease are the same as in the general population, but amplified. Low back pain and back of the neck pain are probably the most common pain conditions in PD. The reason Parkinson’s Disease patients have so many problems with their low back and their neck is their posture. Parkinson’s Disease causes a stooped posture. Some of this happens with age anyway, particularly in women after menopause when their bones soften, but is always worse from the PD. All Parkinson’s Disease patients have some degree of stooped posture and many also tilt to one side. Because of the stooped posture, the muscles in the lower back have to pull much harder to keep the spine upright.

Q What Role Does Exercise Play In Pain Management In Pd

Dr. Fleisher: Exercise and physical therapy can be tremendously helpful in managing pain in PD, in addition to being important for overall disease management.4,8 Evidence suggests that exercise is the best option we have to alter the course of PD, and it has been shown to promote neuroplasticity and neurorestoration in PD.9,10 In addition, research suggests that exercise can activate both dopaminergic and non-dopaminergic inhibitory pain pathways, which may help to modulate the experience of pain in PD.10

Good exercise options include walking, swimming, dancing, and using a recumbent bike. In particular, forms of dance with smooth movements and those that encourage bigger steps appear to be especially beneficial in helping retrain the brain that the shuffling gait of PD is not the norm. Incredible work has come out of the Mark Morris Dance Company, in New York City, which has started a Dance for PD class that has spread throughout the country. In addition, yoga and tai chi can help with balance and core strength, which are critical for people with PD.

Importantly, there doesn’t appear to be an upper limit for the benefits of exercise on the disease. I encourage patients to aim for at least 30 to 45 minutes a day at least 3 to 4 days a week. Patients who are sedentary should start with 5 minutes per day for a week, and then increase the duration each week.

Active Research Into Several Aspects Of Parkinsons Pain

What Does Muscle Pain Feel Like?

Researchers are working to better understand the mechanisms behind pain in Parkinson’s so that it can be more effectively addressed. They are looking for objective measurements, such as brain imaging, to diagnose and monitor pain, and to evaluate response to treatment. And, they’re investigating several drugs and deep brain stimulation for their potential benefits in treating Parkinson’s disease pain.

What Are The Surgical Treatments For Parkinsons Disease

Most patients with Parkinson’s disease can maintain a good quality of life with medications. However, as the disease worsens, medications may no longer be effective in some patients. In these patients, the effectiveness of medications becomes unpredictable – reducing symptoms during “on” periods and no longer controlling symptoms during “off” periods, which usually occur when the medication is wearing off and just before the next dose is to be taken. Sometimes these variations can be managed with changes in medications. However, sometimes they can’t. Based on the type and severity of your symptoms, the failure of adjustments in your medications, the decline in your quality of life and your overall health, your doctor may discuss some of the available surgical options.

What Is The Outlook For Persons With Parkinsons Disease

Although there is no cure or absolute evidence of ways to prevent Parkinson’s disease, scientists are working hard to learn more about the disease and find innovative ways to better manage it, prevent it from progressing and ultimately curing it.

Currently, you and your healthcare team’s efforts are focused on medical management of your symptoms along with general health and lifestyle improvement recommendations . By identifying individual symptoms and adjusting the course of action based on changes in symptoms, most people with Parkinson’s disease can live fulfilling lives.

The future is hopeful. Some of the research underway includes:

  • Using stem cells to produce new neurons, which would produce dopamine.
  • Producing a dopamine-producing enzyme that is delivered to a gene in the brain that controls movement.
  • Using a naturally occurring human protein – glial cell-line derived neurotrophic factor, GDNF – to protect dopamine-releasing nerve cells.

Many other investigations are underway too. Much has been learned, much progress has been made and additional discoveries are likely to come.

How To Deal With The 6 Common Causes Of Leg Pain In Pd

Severe leg pain is a common complaint from people with PD.  Lately, it is understood that central pain is common to Parkinson’s disease, and can even be the first sign of PD, usually bilaterally.  This blog post lists six causes of lower limb pain, and the importance of treating it.  Treatments depend on properly identifying the source of pain.  Some treatment suggestions are included.

What Drug Treatments Are Commonly Prescribed For Pain

Cogwheeling in Parkinson’s Disease: Causes and Treatment

Dopamine agonists are often the neurologist’s first weapon to alleviate Parkinson’s-related pain. Levodopa is used to treat many types of pain due to Parkinson’s because it treats the motor symptoms such as rigidity and dystonia that are causing them.  Other medicines called analgesics can also be used to treat pain. When talking with your doctor, it is critical to let her know about all of the medications you are taking– including over the counter drugs, herbs, vitamins and mineral supplements. Without complete information, your doctor may prescribe a drug that could have serious adverse effects.

What Medications Are Used To Treat Parkinsons Disease

Medications are the main treatment method for patients with Parkinson’s disease. Your doctor will work closely with you to develop a treatment plan best suited for you based on the severity of your disease at the time of diagnosis, side effects of the drug class and success or failure of symptom control of the medications you try.

Medications combat Parkinson’s disease by:

  • Helping nerve cells in the brain make dopamine.
  • Mimicking the effects of dopamine in the brain.
  • Blocking an enzyme that breaks down dopamine in the brain.
  • Reducing some specific symptoms of Parkinson’s disease.

Levodopa: Levodopa is a main treatment for the slowness of movement, tremor, and stiffness symptoms of Parkinson’s disease. Nerve cells use levodopa to make dopamine, which replenishes the low amount found in the brain of persons with Parkinson’s disease. Levodopa is usually taken with carbidopa to allow more levodopa to reach the brain and to prevent or reduce the nausea and vomiting, low blood pressure and other side effects of levodopa. Sinemet® is available in an immediate release formula and a long-acting, controlled release formula. Rytary® is a newer version of levodopa/carbidopa that is a longer-acting capsule. The newest addition is Inbrija®, which is inhaled levodopa. It is used by people already taking regular carbidopa/levodopa for when they have off episodes .

Strengthening Exercises Or Stretching May Be Helpful

Imagine that the spine is like a telephone pole or the mast of a sailboat. If the pole is not exactly upright, even a slight tilt requires a great force to keep it from tilting further and falling. In the human body, this means that the lower back muscles are under great stress. It also means that the tension on the back bones is much increased as well. This worsens whatever problems, like arthritis, that are already present. The same process applies to the neck, although the forces are less great. Strengthening exercises or stretching may be helpful. Almost everyone over the age of 60 has arthritis in their spine. Luckily most don’t have pain from it, but those who do will have it worsened by the spine curvature caused by the PD.

PD patients also frequently have an aching discomfort in their muscles, particularly in the thighs and shoulders. I think this is due to the rigidity, or stiffness, that is part of the Parkinson’s Disease syndrome, but I’ve seen many patients with this pain and no apparent stiffness on examination, hence not explained. It is common and it often, but not always, responds to alterations of the usual Parkinson’s Disease medications for movement. Exercise and stretching may be helpful as well and should always be tried first before increasing medications.

Pain is a challenge in PD. We can’t measure it and often cannot find its cause. It is, however, often treatable, and reducing pain improves quality of life.

What Are The Different Stages Of Parkinsons Disease

Each person with Parkinson’s disease experiences symptoms in in their own unique way. Not everyone experiences all symptoms of Parkinson’s disease. You may not experience symptoms in the same order as others. Some people may have mild symptoms; others may have intense symptoms. How quickly symptoms worsen also varies from individual to individual and is difficult to impossible to predict at the outset.

In general, the disease progresses from early stage to mid-stage to mid-late-stage to advanced stage. This is what typically occurs during each of these stages:

Early stage

Early symptoms of Parkinson’s disease are usually mild and typically occur slowly and do not interfere with daily activities. Sometimes early symptoms are not easy to detect or you may think early symptoms are simply normal signs of aging. You may have fatigue or a general sense of uneasiness. You may feel a slight tremor or have difficulty standing.

Often, a family member or friend notices some of the subtle signs before you do. They may notice things like body stiffness or lack of normal movement slow or small handwriting, lack of expression in your face, or difficulty getting out of a chair.

Mid stage

Mid-late stage

Standing and walking are becoming more difficult and may require assistance with a walker. You may need full time help to continue to live at home.

Advanced stage

Treatment Depends On Properly Identifying The Type

Parkinson’s disease symptoms: Do you often feel like this ...

If pain is bilateral always assume it is central pain; pain due to PD. In my experience Azilect works great for this type of pain. Other medications which can be employed for this pain as well.

Massage therapy works for all types of leg pain-my favorite therapy but can be costly. Water therapy may also work for all types except central pain. Physical therapy can alleviate dystonia pain, as well as musculoskeletal and radicular pain.

If pain is due to dystonia related to levodopa intake, find out when it occurs—end of dose or at peak dose. Typically adjusting medication doses will resolve problem. However, if dystonia is an initial symptom of PD, initiating treatment with levodopa will resolve. If medication adjustment does not work well for levodopa induced dystonia, another treatment option is DBS . Pain due to dystonia independent of cause can also respond well to Botox injections, as well as centrally acting muscle relaxants. To avoid and alleviate pain caused by stiff muscles, a great treatment option is activity in the form of stretching exercises—any number of activities will do such as tai-chi or yoga. For me when I start having radicular pain shooting down my leg it is time to up my levodopa dosage.

If you are having leg pain make sure to discuss it with your physician.

Incidence And Prevalence Of Pd General Pain And Pd

Estimates of PD prevalence and incidence have provided conflicting estimates. In Europe, the annual incidence estimates range from 5/100,000 to 346/100,000.2 Approximately 60,000 Americans are diagnosed with PD each year.3 The challenges involved with differential diagnoses and other forms of Parkinsonism, as well as the long time course from initial PD-like symptoms to a correct diagnosis, are likely responsible for the discrepancy in numbers.4

The reported prevalence of pain in PD and PD-related pain also varies between studies. In 2008, Negre-Pages et al5 estimated the prevalence of chronic pain in PD to be >60%. PD pain is often reported as heterogeneous in its clinical presentation, with a disabling effect on quality of life assessments. In 1998, the Swedish Parkinson Association reported on a survey of nonmotor symptoms comprising almost 1,000 PD respondents, revealing that pain was more common in females than males .6 However, general pain is also common in the population, with 18%–19% in a general adult population according to the prevalence data.7,8

In early-stage PD, pain is rated as one of the most troublesome NMS,9 and it seems to affect the side of the body that was initially worst impacted by motor symptoms of the disease .10


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