Among the numerous non-motor symptoms affecting patients with Parkinson’s disease (PD), chronic pain has become a topic of increasing focus in recent years. In studies investigating the prevalence of pain in PD, figures have ranged from 30%-85% due to between-study differences in factors such as diagnostic criteria, sample sizes, and assessment methods used.1
In a study that examined analgesic prescriptions as an indicator of pain, the prevalence of chronic pain was 33% in PD compared with 20% in the general population. In addition, PD patients were more frequently prescribed antidepressant and antiepileptic drugs compared to the general population as well as patients with osteoarthritis and diabetes, possibly due to physician recognition and subsequent treatment of neuropathic pain in the PD patients.1
In a paper published in October 2020 in Revue Neurologique, Marques and Brefel-Courbon examined the available literature regarding various aspects of pain in PD. Key points from the review are discussed below. 1
Impact on Quality of Life
Findings have shown that pain may have a greater impact on quality of life than motor symptoms in some patients with PD, and a significant link has been noted between pain and depression in PD. However, as in the general population, pain predicts reduced quality of life in PD independently of depression.
Studies suggest that the main factors predicting the development of pain in PD are female sex, motor complications, dyskinesia, postural impairment, and depression. Some research indicates that pain in PD may also be associated with younger age and early disease stage, while other studies have reported evidence to the contrary. These conflicting results regarding the relationship between PD stage and pain “could be related to different pain subtypes occurring at different moments in the course of PD,” wrote the review authors.1
According to a well-known model, there are 5 subtypes of pain in PD, including musculoskeletal pain, radicular or neuropathic pain, dystonia-related pain, primary or central pain, and pain from akathisia.2 Many patients suffer from more than 1 of these pain subtypes – for example, in a study of 100 PD patients, nearly one-half had experienced 2 or more types of pain in the previous week.3
Marques and Brefel-Courbon note the important clinical implications of these observations, given the distinct treatment approaches required for each type of pain described, which may include acetaminophen, NSAIDs, dopaminergic agents, antidepressants, opioids, physical therapies, deep brain stimulation among others.1,4 However, there is a need to further elucidate definitions of and distinctions between the pain subtypes in PD to improve treatment of these patients.
Classification of Pain in PD
Limitations have been noted for each of several proposed systems of classification for pain in PD, most commonly pertaining to unclear definitions and lack of specificity for different pain types. For parkinsonian central pain (PCP), the most severe and poorly characterized type, the current authors and colleagues recently proposed standardizing this diagnosis through a process of exclusion based on classification of pain as nociceptive, neuropathic, or nociplastic pain (similar to the classification of chronic pain in the general population), and specific or unspecific to PD.5
They developed an algorithm that aims to “disentangle PCP from other chronic pain subtypes in PD by specifically and sequentially ruling out what is not PCP,” they explained.1 “A better classification of pain in PD is crucial in order to homogenize the populations in studies aiming to improve our comprehension of pathophysiological mechanisms of pain in PD.”
Numerous studies have demonstrated abnormal pain processing in PD – including reduced thresholds for the perception of pain – which likely primarily originates in the central nervous system. In research using functional imaging to compare patients with PD with vs those without pain, findings revealed preferential recruitment of the medial affective pathway in those with pain, while those without pain showed greater activation in the lateral discriminative nociceptive areas.6 This study also found that levodopa decreased nociceptive perception in PD patients regardless of pain status.
The imaging results suggest that pain in PD may stem from an imbalance between the discriminative and affective systems, according to Marques and Brefel-Courbon.1 These observations align with those of other studies using structural and function magnetic resonance imaging, which found thinning and functional changes in multiple nociceptive brain regions in PD patients with pain compared to those with no pain.
Taken together, these results point to the existence of pain-specific regional brain modifications in PD patients with chronic pain. Pain-related overactivation of nociceptive areas on functional MRI has been found in PD patients with pain – with and without previous exposure to dopaminergic drugs.1 Overall, the “role of the dopaminergic system in the pathophysiology of pain remains an open question,” the review authors stated.1 Several “neurotransmitters such as dopamine, norepinephrine, serotonin and opioid could participate in the abnormal pain processing in PD.” Much additional research is needed to clarify these and other questions pertaining to the role and nature of pain in PD.
1. Marques A, Brefel-Courbon C. Chronic pain in Parkinson’s disease: Clinical and pathophysiological aspects. Published online October 3, 2020. Rev Neurol (Paris). doi:10.1016/j.neurol.2020.06.015
2. Ford B. Pain in Parkinson’s disease. Clin Neurosci. 1998;5(2):63-72. PMID:10785830
3. Valkovic P, Minar M, Singliarova H, et al. Pain in Parkinson’s disease: a cross-sectional study of its prevalence, types, and relationship to depression and quality of life. PLoS One. 2015;10(8):e0136541. doi:10.1371/journal.pone.0136541
4. Edinoff A, Sathivadivel N, McBride T, et al. Chronic pain treatment strategies in Parkinson’s disease. Neurol Int. 2020;12(3):61-76. doi:10.3390/neurolint12030014
5. Marques A, Attal N, Bouhassira D, et al. How to diagnose parkinsonian central pain? Parkinsonism Relat Disord. 2019;64:50-53. doi:10.1016/j.parkreldis.2019.04.025
6. Brefel-Courbon C, Ory-Magne F, Thalamas C, Payoux P, Rascol O. Nociceptive brain activation in patients with neuropathic pain related to Parkinson’s disease. Parkinsonism Relat Disord. 2013;19(5):548-552. doi:10.1016/j.parkreldis.2013.02.003