Practical Pain Management interviewed Jori E. Fleisher, MD, MSCE, assistant professor of neurology and population health at The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders at NYU Langone Medical Center (New York CIty), a Parkinson’s Foundation Center of Excellence, about the challenges facing women with Parkinson's disease.
Chronic pain occurs in 30% to 85% of patients with Parkinson’s disease (PD), particularly in women, and is one of the strongest predictors of poor quality of life in patients with this disease.1,2 Dr. Fleisher responds to questions that offer clinicians insights into the pain experienced by women who have Parkinson's disease.
Q. What is the pain experience in PD, and does it differ between genders?
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. Pain intensity also is higher in women than in men with PD.
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. What are the causes of pain in PD?
Dr. Fleisher: There are 4 primary types of pain in PD: musculoskeletal, dystonic, neuropathic, and central pain.2
• Musculoskeletal pain typically is related to involuntary muscle rigidity or bradykinesia, which limits range of motion. For example, it is not uncommon for people with PD to present initially with unilateral shoulder pain (ie, frozen shoulder) for which they have undergone numerous orthopedic and pain management consultations, as well as failed injections and surgeries, before they consult with a neurologist or a movement disorder specialist and are correctly diagnosed with PD.
• Dystonic pain usually manifests as painful curling or bending of the toes/fingers or inversion of one foot but can occur in any area of the body. Sometimes, dystonic pain is a sign of extremely low dopamine levels, especially when it occurs first thing in the morning or late at night.
• Neuropathic pain in PD commonly is related to neuroforaminal compression in the spine resulting from degenerative disc disease, but it also may be related to nerve compression that causes a twisting of the spine in a person with dystonia, or postural deformities related to PD.
Central pain is relatively rare, occurring in approximately 10% of people with PD at some point.4 Symptoms include a vague gnawing, boring, or deep, aching pain that is often hard to describe and may be unrelenting. In some cases, central pain can show up as abdominal pain or a feeling of reflux without a clear etiology. Rarely, people with PD may have perioral/oral pain or genital pain as a manifestation of this central pain syndrome. Because the symptoms of central pain are vague and the syndrome is poorly understood by nonpain specialists, there may be a tendency for physicians and healthcare providers to minimize the symptoms or at least not recognize them as a part of 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.
Q. What is the role of depression in the pain experience in PD?
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 (AEs). The patient fills out the subjective component every single time they come to the office.
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.
One way to incentivize exercise is to reserve your favorite television shows only for times that you are exercising. This can be helpful in motivating people to stick with a regimen. If a patient is going to binge watch TV, they should reserve that time for when they are on a recumbent bike, treadmill, or elliptical machine.
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 (eg, rigidity, bradykinesia, dystonia) 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 (eg, diabetes, osteoarthritis, depression) 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 (eg, foot drop). Thus, patient counseling is important to manage expectations.
For neuropathic pain, anticonvulsants such as gabapentin (Neurontin, Gralise, others) or pregabalin (Lyrica) can be effective. As second-line therapy, tricyclic antidepressants may be effective. However, in many patients, the adverse effects of those medications, particularly the anticholinergic effects (eg, confusion, dry mouth, urinary retention, or constipation)—which patients already may experience as symptoms of PD—outweigh the benefits.
Central pain is the most difficult type of pain to treat. Antidepressants (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or atypical antidepressants) or anticonvulsants (gabapentin or pregabalin) may be helpful. In select cases, opioids may be necessary. Consultation with a pain management specialist for additional expertise is warranted in these difficult cases.
When treating women of childbearing age, it is important to make sure that medications are appropriate for women who are pregnant or breastfeeding or who want to become pregnant. Consultation with the patient’s OB/GYN may be warranted in some cases to rule out contraindications.
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. 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.