Parkinson's Disease and Chronic Pain

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Chronic pain is very common in Parkinson's disease, affecting more than two thirds of all patients, and it tends to worsen as the disease progresses.[1] The spine is the most frequent area of pain. Patient's usually don't realise that pain is part of the disease process. There is a lack of data around how to effectively manage pain in those affected.

Classification

There have been multiple classification schemes for pain in Parikinson's Disease.The classification system by Ford is the most well known (Table 1). It classifies pain into musculoskeletal, radicular/neuropathic, dystonia-related, akathic discomfort/pain, and central pain. Another more recent classification scheme is to use the standard nociceptive, neuropathic, and nociplastic descriptors.

Musculoskeletal nociceptive type pain is considered to be the most frequent type of pain. However in Parkinson's Disease pain thresholds are lowered. For example in the presence of radiographic osteoarthritis, pain is twice as common, suggesting that central processes are also important.[2][3] Ultimately, it is difficult in clinical practice to differentiate between different purported pain mechanisms. Furthermore, because Parkinson's disease occurs later in life, it is also common to have non Parkinson's disease associated pain (i.e. Hickums dictum).

Table 1. Ford's pain classification[4]
Pain type Pain features
Musculoskeletal pain
  • Aching, cramping, arthralgic, myalgic sensations in joints, and muscles;
  • Associated findings may include muscle tenderness, arthritic changes, skeletal deformity, limited joint mobility, postural abnormalities, and antalgic gait;
  • May be exacerbated by parkinsonian rigidity, stiffness, and immobility, and relieved by mobility;
  • May fluctuate with medication dosing, and improve with levodopa
Radicular/neuropathic pain
  • Pain in a root or nerve territory, associated with motor or sensory signs of nerve or root entrapment
Dystonic pain
  • Associated with sustained twisting movements and postures; muscular contractions often very forceful and painful;
  • Dystonia may involve any limb or extremity, as well as facial and pharyngeal musculature;
  • May fluctuate closely with medication dosing: early morning dystonia, off dystonia, beginning-of-dose and end-of-dose dystonia, peak dose dystonia
Central or primary pain
  • Burning, tingling, formication, ā€˜ā€˜neuropathicā€™ā€™sensations, often relentless and bizarre in quality, not confined to root or nerve territory;
  • Pain may have an autonomic character, with visceral sensations or dyspnea, and vary in parallel with the medication cycle as a non-motor fluctuation;
  • Not explained by rigidity, dystonia, musculoskeletal or internal lesion
Akathisia
  • Subjective sense of restlessness, often accompanied by an urge to move;
  • May fluctuate with medication effect, and improve with levodopa

Pathophysiology

Central pain:

Central pain in Parkinson's Disease (PD) arises from disturbances in pain processing and perception within the ascending and descending pathways. These disturbances are due to the involvement of numerous pain processing structures that are directly implicated in the spread of PD pathoanatomy within the nervous system across different neuropathological stages. The basal ganglia play a significant role in central pain processing, with dopaminergic deficits leading to reduced multimodal pain thresholds. Spinal excitability alterations and local neurodegenerative changes, such as painful hyperactivity in primary afferent nociceptors and diminished dopaminergic descending inhibition, are pathophysiologically relevant in PD.

Moreover, the impact of dopaminergic replacement therapy on pain thresholds remains controversial, particularly for levodopa. Abnormal central nociceptive pain processing is influenced by other neurodegeneratively affected regions in PD, including cortical areas, limbic structures, thalamus, brainstem nuclei, periaqueductal grey matter, and the spinal cord. Additionally, molecular alterations in the cytoskeleton and mitochondria in PD may contribute to nociceptor hyperactivity, resulting in neuropathic pain and increased pain sensitivity due to reduced nociception thresholds.[1]

Nociceptive pain

Pain in PD patients is more commonly observed as musculoskeletal or nociceptive pain rather than central pain, with roughly half of the PD population experiencing pain due to secondary diseases such as spinal or peripheral joint osteoarthritis. Although this pain may be exacerbated by akinesia and rigidity, there is no clear correlation between the severity of motor symptoms and reported pain levels. This suggests that pain and motor impairment may not share identical pathogenetic mechanisms.

It is important to consider that musculoskeletal pain, particularly on one side of the body (e.g., shoulder-arm syndrome) and adhesive capsulitis, is a common early manifestation of akinesia and rigidity in PD. This type of pain may be frequently misdiagnosed or overlooked, further complicating the understanding of pain presentation and progression in PD patients.

Risk Factors

Risk factors for pain include female gender, dyskinesia, postural abnormalities, motor complications, depression, diabetes mellitus, osteoporosis, rheumatic diseases, and arthritis.

Postural Deformities

Spinal deformities are common complications in PD that significantly impact patients' quality of life and are associated with chronic spinal pain. These postural abnormalities typically manifest as a result of the progressive nature of the disease, affecting muscle tone, balance, and movement control. Various spinal deformities have been identified in PD patients, each presenting distinct characteristics and degrees of severity.

  • Camptocormia is characterized by severe flexion (over 45Ā°) of the thoracolumbar spine in the sagittal plane during standing and walking, which almost completely resolves when in a recumbent position.
  • Antecollis involves severe forward flexion (over 45Ā°) of the head in the sagittal plane, partially correctable by voluntary movement, but incapable of fully extending the neck against gravity. Although rare in Parkinson's disease, it is frequently observed in multiple system atrophy.
  • Retrocollis is an abnormal neck posture held in extension in the sagittal plane, which is rare in Parkinson's disease but typical of progressive supranuclear palsy.
  • Scoliosis is defined as a flexion (over 10Ā°, as per the Cobb method) of the spine in the coronal plane, uncorrectable by voluntary or passive movement, and accompanied by axial rotation of the vertebrae, as confirmed by radiograph.
  • Pisa syndrome: is a reversible lateral bending of the trunk with a tendency to lean to one side (over 10Ā°)

Management

Unfortunately there is limited data guiding the treatment of pain in PD. Furthermore no specific treatments exist. Medications include dopaminergic drugs, non-opoid drugs, opioids, anticonvulsants, and antidepressants. Unfortunately, pain is often resistant to treatment.[5] Practically the first step is usually to optimise dopaminergic therapy.[6]

Spinal surgery is considered a relative contraindication in PD. Parkinson's disease presents significant challenges in the context of spinal surgery due to the prevalence of complications such as construct or fusion-related issues, infection, and a frequent requirement for revision surgery. These complications mainly arise from progressive kyphosis or spine segmental instability, with postoperative sagittal imbalance being a primary factor contributing to construct failure and necessitating revision surgery. Risk factors that contribute to surgical complications in patients with Parkinson's disease include advanced stages of the disease, severe disability, and poor functional status. These factors make spinal surgery more complex and demanding, increasing the likelihood of complications and the need for additional intervention.[7]

Resources

References

  1. ā†‘ 1.0 1.1 Buhmann, Carsten; Kassubek, Jan; Jost, Wolfgang H. (2020). "Management of Pain in Parkinson's Disease". Journal of Parkinson's Disease. 10 (s1): S37ā€“S48. doi:10.3233/JPD-202069. ISSN 1877-718X. PMC 7592654. PMID 32568113.
  2. ā†‘ NĆØgre-PagĆØs, Laurence; Regragui, Wafa; Bouhassira, Didier; Grandjean, HĆ©lĆ©ne; Rascol, Olivier; DoPaMiP Study Group (2008-07-30). "Chronic pain in Parkinson's disease: the cross-sectional French DoPaMiP survey". Movement Disorders: Official Journal of the Movement Disorder Society. 23 (10): 1361ā€“1369. doi:10.1002/mds.22142. ISSN 1531-8257. PMID 18546344.
  3. ā†‘ Mylius, Veit; Perez Lloret, Santiago; Cury, Rubens G.; Teixeira, Manoel J.; Barbosa, Victor R.; Barbosa, Egberto R.; Moreira, Larissa I.; Listik, Clarice; Fernandes, Ana M.; de Lacerda Veiga, Diogo; Barbour, Julio (2021-04-01). "The Parkinson disease pain classification system: results from an international mechanism-based classification approach". Pain. 162 (4): 1201ā€“1210. doi:10.1097/j.pain.0000000000002107. ISSN 1872-6623. PMC 7977616. PMID 33044395.
  4. ā†‘ Ford, Blair (2010). "Pain in Parkinson's disease". Movement Disorders: Official Journal of the Movement Disorder Society. 25 Suppl 1: S98ā€“103. doi:10.1002/mds.22716. ISSN 1531-8257. PMID 20187254.
  5. ā†‘ Jost, Wolfgang H.; Buhmann, Carsten (2019-10). "The challenge of pain in the pharmacological management of Parkinson's disease". Expert Opinion on Pharmacotherapy. 20 (15): 1847ā€“1854. doi:10.1080/14656566.2019.1639672. ISSN 1744-7666. PMID 31290336. Check date values in: |date= (help)
  6. ā†‘ Mylius, Veit; Mƶller, Jens Carsten; Bohlhalter, Stephan; Ciampi de Andrade, Daniel; Perez Lloret, Santiago (2021-07). "Diagnosis and Management of Pain in Parkinson's Disease: A New Approach". Drugs & Aging. 38 (7): 559ā€“577. doi:10.1007/s40266-021-00867-1. ISSN 1179-1969. PMID 34224103. Check date values in: |date= (help)
  7. ā†‘ Barone, Paolo; Santangelo, Gabriella; Amboni, Marianna; Pellecchia, Maria Teresa; Vitale, Carmine (2016-09). "Pisa syndrome in Parkinson's disease and parkinsonism: clinical features, pathophysiology, and treatment". The Lancet. Neurology. 15 (10): 1063ā€“1074. doi:10.1016/S1474-4422(16)30173-9. ISSN 1474-4465. PMID 27571158. Check date values in: |date= (help)