Pain in Parkinson’s disease: classification and management

With Dr Panagiotis Zis and Professor Kallol Ray Chaudhuri  |  27 Apr 2015  |  Print

Pain in Parkinson’s disease: classification and management

Dr Panagiotis Zis is from the National Parkinson Foundation International Centre of Excellence, King’s College Hospital NHS Foundation Trust, London; Professor Kallol Ray Chaudhuri is Lead, National Parkinson Foundation Centre of Excellence, King’s College, Denmark Hill Campus and Lead, Nervous System, South London Comprehensive Local Research Network, London, UK.

Pain is a frequent yet poorly understood non-motor symptom of Parkinson’s disease (PD), sometimes severe enough to overshadow the motor symptoms of the disorder. James Parkinson himself observed that painful symptoms can be an early and presenting symptom of the disease that bears his name, and this is now widely recognised.[1,2] However, pain can occur throughout all stages of PD, and it exhibits considerable heterogeneity.[3] Despite the fact that it is one of the most common non-motor symptoms adversely affecting quality of life in people with PD,[4,5] pain in PD continues to be neglected and poorly managed.

Epidemiological studies show that the prevalence of pain in PD may be as high as 80%.[5] In a large systematic review, Broen et al found that prevalence ranges from 40% to 85% with a mean of 67.6% across the studies.[6] In a recent retrospective study, pain was reported as the initial symptom by 15% of the PD patients.[7] The precise nature of early or premotor pain in PD remains to be characterized.

Classification of pain in PD

The most commonly used classification system was proposed by Ford in 1998,[8,9] and includes five different categories of pain in PD:

  • Musculoskeletal
  • Radicular/neuropathic
  • Pain associated with dystonia
  • Central or primary pain
  • Pain associated with akathisia (restlessness).

In 2009, Chaudhuri and Schapira proposed a classification of distinct pain syndromes in PD.[10] This classification includes:

  • Musculoskeletal pain
  • Chronic pain (central or visceral)
  • Fluctuation-related pain
  • Nocturnal pain
  • Coat-hanger pain
  • Orofacial pain
  • Peripheral limb or abdominal pain.

This classification also categorizes pain syndromes based on whether or not they respond to dopaminergic therapy.

The first pain scale specifically for PD patients has been designed by Chaudhuri et al, has been validated and is currently awaiting publication.[11]

Management of pain in PD

Pain in PD is multifactorial and may or may not be related to the underlying disease process. For instance, in patients with PD, pain unrelated to PD arises from comorbidities such as osteoarthritis. In these cases, the treatment algorithm relevant to the underlying comorbidity should be applied. However, for pain that can specifically be attributed to PD, there are as yet no validated and evidence-based treatment algorithms, as studies published until now have provided only weak evidence. Treatment options include dopaminergic and non-dopaminergic drug therapy, and non-pharmacological therapy. In Figure 1 we propose a treatment algorithm based on current knowledge and personal practice.

 pain assessment

Figure 1. Proposed algorithm for management of pain in PD*

*Please note that not all of these treatments are licensed for use in this setting. Please refer to individual prescribing information for details.

Dopaminergic options
Levodopa alters the pain threshold in people with PD.[12] Schesatsky et al demonstrated that conduction along peripheral and central pain pathways is within normal limits in PD patients regardless of whether they experience primary central pain; however they fail to habituate to repetitive pain stimulation. This suggests an atypical regulation of autonomic centers controlling sympathetic sudomotor responses. It implies that this dysfunction may occur in centers dependent on dopamine-regulating autonomic function and inhibitory modulation of pain inputs, and can be at least in part attenuated by levodopa.[12] Apart from oral levodopa, current open label and comparative data suggest that intrajejunal levodopa infusions are beneficial for non-motor symptoms including pain, and improve health-related quality of life in PD in addition to improving motor fluctuations and dyskinesias.[13,14]

Dopamine agonists, especially those offering continuous drug delivery such as the rotigotine patch or subcutaneous apomorphine infusion, have also been shown to improve pain in PD[15-18] although evidence with the latter is conflicting.[17,18] However, dopamine agonists may also be the cause of edema, leading to pain in the extremities[19] or, rarely, pain associated with retroperitoneal fibrosis,[20] which has been associated with ergot-derived dopamine agonists.

Non-dopaminergic options 
Opioids, in particular prolonged release opioid formulations, are often used to treat chronic pain. A multicenter, double-blind, randomized, placebo-controlled, parallel-group study into the efficacy of prolonged release oxycodone/naloxone in controlling Parkinson’s disease-related chronic severe pain in male and female subjects (the PANDA study) has recently been completed and the results are awaited.[21]

In a small study that included 23 patients, duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has been found to be effective for the treatment of central pain in PD (unlicensed use).[22] Very recently, in an open-label observational study, it has been suggested that cannabis might have a place in the therapeutic armamentarium of PD.[23]

Non-pharmacological – deep brain stimulation.
Deep brain stimulation is a non-pharmacological measure that has been shown to improve ‘off’ pain (that is, pain that occurs after the effects of levodopa have worn off)[24] and has a beneficial effect that lasts for at least 24 months.[25] In some subjects, a new pain (mostly musculoskeletal in quality), had developed by this time point.[25] Pallidal deep brain stimulation has demonstrated improvement for ‘off’ period dystonia and other sensory symptoms in patients with advanced PD.[26]

A multidisciplinary approach

The role of multidisciplinary therapy in the management of pain in PD is paramount. Focused physiotherapy can significantly improve the aching, cramping sensation associated with musculoskeletal pain as well as radicular pain. The therapeutic strategy may also benefit from input from occupational therapists or referral to a pain team. Finally, pain may be a dominant issue in the palliative stage of PD and input from a palliative care team may therefore be important.

References:

  1. 1. Parkinson J. An Essay on the Shaking Palsy. London, Sherwood, Neely, and Jones, 1817.
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  3. 3. Wasner G, Deuschl G. Pains in Parkinson disease–many syndromes under one umbrella. Nat Rev Neurol 2012;8:284-294.
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  7. 7. O’Sullivan SS, Williams DR, et al.  Nonmotor symptoms as presenting complaints in Parkinson’s disease: a clinicopathological study. Mov Disord 2008;23:101-106.
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  11. 11. Rizos AM, Martinez-Martin P, et al. Mov Disord 2014;29(Suppl 1):S190-S192. Poster 510.
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  19. 19. Kleiner-Fisman G, Fisman DN. Risk factors for the development of pedal edema in patients using pramipexole. Arch Neurol 2007;64:820-824.
  20. 20. Kvernmo T, Härtter S, et al. A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Thera 2006;28:1065-1078.
  21. 21. Mundipharma Research GmbH & Co KG. A Randomised Placebo Controlled Study of OXN PR for Severe Parkinson’s Disease Associated Pain. Available at: www.clinicaltrials.gov/ct2/show/NCT01439100. Accessed November 2014.
  22. 22. Djaldetti R, Yust-Katz S, et al. The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin Neuropharmacol 2007;30:201-205.
  23. 23. Lotan I, Treves T, et al. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin Neuropharmacol 2014;37:41-44.
  24. 24. Kim HJ, Paek SH, et al. Chronic subthalamic deep brain stimulation improves pain in Parkinson disease. J Neurol 2008;255:1889-1894.
  25. 25. Kim HJ, Jeon BS, et al. The benefit of subthalamic deep brain stimulation for pain in Parkinson disease: a 2-year follow-up study. Neurosurgery 2012;70:18-23;discussion 23-24.
  26. 26. Loher TJ, Burgunder JM, et al. Effect of chronic pallidal deep brain stimulation on off period dystonia and sensory symptoms in advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 2002;73:395-399.

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