Definition | Diagnostic criteria | Epidemiology | Risk Factors | Pathophysiology | Presentation | Examination | Differential diagnosis | Investigations | Management | Prognosis | Golden Pearls | Quiz | References/Articles/Resources |
Definitions/Diagnostic criteria (Edinoff et al., 2020)
"Parkinson’s disease is a widely described, physically and mentally disabling neurodegenerative disorder that is most often recognizable in patients by the presence of three cardinal motor signs: resting tremor, bradykinesia, and muscular rigidity."
One symptom often poorly recognized and under-treated by health care providers despite being reported as the most common non-motor symptom is the finding of chronic pain
Epidemiology (Edinoff et al., 2020)
Neurological disorders are rapidly becoming the primary cause of disability, of which Parkinson’s disease (PD) is the fastest growing with a doubling in cases between 1995 and 2015 (to 6 million) and another doubling projected by 2040.
PD is the most common movement disorder and the second most common neurodegenerative disorder of the central nervous system. The disease affects around 3% of the population by age 65 and up to 5% of people over the age of 85
Prevalence of 100 to 200 per 100,000 people, with annual incidence estimates ranging from less than 10 to more than 20 per 100,000 in the total population
Median incidence rate of 160 per 100,000 in the population aged 65 years or older and peaking in most studies between the ages of 70 and 79 years
PD is rare prior to 50yo
Men > Women / 1.5 : 1
While it is understood that some level of pain is caused and/or made worse by PD, the presentation of pain in patients is greatly varied in type and severity, with some patients reporting no pain and others experiencing several modalities of pain ranging from minor to moderate and severe
Pain occurs in 30-85% of patients with PD
Compared to the general population of similar age, Parkinson’s patients have been confirmed to suffer from a significantly higher level and prevalence of pain
The types of chronic pain understood to be resulting from or exacerbated in the Parkinson’s patient are musculoskeletal pain, dystonic pain, nerve pain, primary pain, akathitic pain, and gastrointestinal
Risk factors (Edinoff et al., 2020)
Pesticide exposure (rotenone)
Traumatic brain injury
(Protective factors: Cigarette smoking, caffeine, physical activity, and high serum rate)
Pathophysiology (Edinoff et al., 2020; Brunner & Gerberich, 2021)
PD is defined by loss of dopaminergic neurons in the substantia nigra with deposition of intraneuronal aggregates composed of α-synuclein, called Lewy bodies, in affected areas. Lewy body pathology in PD not only involves cells that produce dopamine, but also those responsible for producing acetylcholine, norepinephrine, serotonin, histamine, and glutamate, accounting for its wide spectrum of clinical symptoms
The primary cause and the mechanisms driving the spread of pathology in PD remain unclear.
There is likely a genetic component - specific genes have been found/replicated across approximately 5% of the PD population
Individuals with Parkinson’s may have increased pain sensitivity, which may be a result of a reduced nociception threshold that can occur regardless of the stage of progression of the disease (Brunner & Gerberich, 2021)
Presentation (Edinoff et al., 2020; Brunner & Gerberich, 2021)
Onset is typically between 65 and 70 years of age
Many patients have prodromal symptoms before typical parkinsonian symptoms
Motor parkinsonism as the core feature, defined as bradykinesia in combination with resting tremor, rigidity or both - these are typical asymmetrical
As the disease progresses, spontaneous movements decrease, facial expressions diminish, speech becomes monotone, and writing often becomes small
Gait changes are also noted, characterized by an asymmetric reduction in arm swing with decreased stride length and walking speed
Pain is the most frequent non-motor PD presentation, typically involving the motor-affected side
Questionnaires are available specifically for pain in PD - the King's PD Pain Scale (KPPS)
Dysautonomia is seen in virtually all PD patients, with symptoms of orthostasis affecting nearly half i.e., hyperhidrosis, orthostatic hypotension, sexual-urinary dysfunction, thermoregulation changes, cardiovascular disturbances, peripheral edema, dilated pupillae), sleep disturbances, neuropsychiatric problems, i.e., apathy, fatigue, anhedonia, depression, anxiety, panic attacks, dementia, psychosis, and sensory, i.e., internal tremor, restless leg syndrome, numbness, paresthesia, visual disturbances, and pain
Cognitive decline involving problems in executive function are also seen, with the diagnosis of dementia being made in approximately 50% of PD patients within 10 years
During “off” periods (described above), when dopaminergic agents are not optimized and motor symptoms are uncontrolled, patients report pain more frequently than when motor symptoms are controlled during “on” periods
Musculoskeletal pain:
Occurs in 45-90% of patients
Caused by muscular rigidity such as frozen shoulder and back pain (most common)
Joint pains are common due to muscle wasting and skeletal deformation
Loss of strength and balance with decreased bone density leads to associated harms
Dystonic pain:
Dystonia is an uncontrolled muscle contraction accompanied by a deformed posture, usually in the hands and feet of a Parkinson’s patient
Studies show that 15–40% of Parkinson’s patients with pain report dystonic character
Current belief is that chronic treatment with levodopa dysregulates striatal cholinergic signaling and synaptic plasticity, possibly due to epigenetic alterations taking place over time
It causes pain and inconvenience when there is prolonged muscle contraction recurring, such as plantar flexion of the toe, which impairs simple tasks like walking or wearing shoes
Peripheral and Central Neuropathic Pain
1/4 of PD patients report nerve pain
Radicular pain from postural change and bone deformities in PD
Peripheral neuropathic has symptoms of tingling, numbness, and general pain
(Thought to be due to decreased B12, MMA and/or homocysteine due to levodopa-induced malabsorption. Alternatively, PD itself may cause the pain with damage to nerve fibres)
Primary, or central pain, is thought to be driven directly by PD pathology and is described to be unexplainable stabbing, burning, or scalding sensations in 4–10% of patients with pain. It is known to be very painful, poorly understood, and difficult to treat.
Strangely the central pain sensitisation processes in PD are thought to be due to dopaminergic changes - affecting the emotional-motivation aspects of pain rather than the sensory-discriminative
Lewy bodies also occur in areas of the brain winvolved in the emotional-motivational aspects of pain - that may also affect pain sensation
Akasthisia
Akathisia refers to an unpleasant agitating sensation that is reported in about 20% of Parkinson’s patients usually in the form of “restless legs syndrome”
Although not all patients report akathisia as being a strictly painful sensation, it is known to cause insomnia and discomfort that can be treated if the health provider is able to recognize it
In addition, a potential source for chronic pain are the various gastrointestinal abnormalities seen in PD. These include dysphagia, constipation, impaired gastric emptying, and problematic absorption, which could lessen the effects of oral antiparkinsonian treatments and diminishes quality of life in about half of patients with PD
Examination
Differential diagnosis
Tremor disorders
Drug-induced Parkinsonism
Vascular parkinsonism
Alzheimer's disease
Parkinsons-plus syndromes (MSA, PSP, Cortical-basal ganglionic degeneration, dementia with Lewy bodies)
Investigations
Treatment (Edinoff et al., 2020; Brunner & Gerberich, 2021)
Achieving satisfactory outcomes when managing chronic pain in PD patients is exceptionally challenging
The extensive heterogeneity of pain that is experienced in PD patients presents obstacles in identifying targets for treatment.
Furthermore, a lack of controlled studies has left a dearth of evidenced based treatment recommendations, and current regimens are largely based on case reports and empirical evidence
Dopamine Agonists
Many of the clinical manifestations of PD are the result of neurodegeneration involving dopaminergic pathways in the CNS. As such, dopaminergic agents have long been a mainstay of PD treatment. The influence of dopamine specifically in PD related pain is less defined however, and thus, the role of dopamine agonism in the treatment of these symptoms is unclear.
While further research is needed to help to refine the use of dopaminergic agents to treat PD related pain, this suggests that optimizing dopaminergic therapy is a valuable step.
Other Pharmacological
NSAIDs are commonly used
Opioids are difficult due to unpleasant neuropsychiatric and GI side effects (they suggest considering Oxycontin/Naloxone - From the PANDA trial)
GABA analogs such as pregabalin or gabapentin may be used for widespread neuropathic pain to avoid opioids
Topical agents, such as capsaicin and lidocaine, may be appropriate for patients with localized neuropathic pain to limit systemic medication exposure.
TCAs can induce constipation complications and anticholinergic side effects
SNRI has similar benefit without the anticholinergic side effects (duloxetine has been studied with 65% of patients mentioning improvement)
Botox has been used for posturing and spasms
Non-Pharmacologic Therapies
Deep brain stimulation of the subthalamic nucleus has been shown to help with some of the PD symptoms
It improved dystonic pain in 100% of patients, central pain in 92%, and radicular pain in 63%, and MSK pain in 61%
These may be direct effects of stimulation on the subthalmic nuclei inducing increased pain thresholds and pain tolerance, and reducing pain-induced cerebral activity in the somatosensory cortex. Benefits may last for up to 8 years!
Surgical ablation of the globes pallidus (pallidotomy) has been used but is not as effective as deep brain stimulation. The theory is that the GP in PD inhibits movement control messages in the thalamus leading to movement occurring more naturally. Exact mechanism remains unclear.
Complementary/alternative therapies
Massage therapy can be helpful
Acupuncture may be of benefit
Exercise and physical therapy is important
Yoga helps back pain
Cannabis has had some beneficial finding
Prognosis
Golden pearls
Quiz
References / Articles / Resources
Edinoff, A., Sathivadivel, N., McBride, T., Parker, A., Okeagu, C., Kaye, A. D., ... & Urits, I. (2020). Chronic Pain Treatment Strategies in Parkinson’s Disease. Neurology International, 12(3), 61-76.
Brunner, R., & Gerberich, A. (2021). Managing Pain in Parkinson’s Disease: Current and Emerging Pharmacologic Treatments. Practical Pain Management. https://www.practicalpainmanagement.com/treatments/pharmacological/managing-pain-parkinson-disease
Fil, A., Cano-de-la-Cuerda, R., Muñoz-Hellín, E., Vela, L., Ramiro-González, M., & Fernández-de-Las-Peñas, C. (2013). Pain in Parkinson disease: a review of the literature. Parkinsonism & related disorders, 19(3), 285-294.
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