Pain as non-motor complication of Parkinson's Disease - Pathos

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Pain as non-motor complication of Parkinson's Disease

El dolor como complicación no motora
de la enfermedad de Parkinson
Clinical report
Pathos 2018, 25; 3. Online 2018, November 27
  https://doi.org/10.30458/PA2018-192
_______________________________________________________________________
Anelys Sánchez López
Medicina Fisica, Universidad de Ciencias Médicas de la Habana
Centro Internacional de Restauración Neurológica (CIREN)
Arnoldo Padrón Sánchez
Medicina Interna, Universidad de Ciencias Médicas de la Habana
Centro Internacional de Restauración Neurológica (CIREN)
Dania Gutiérrez Fernández,
Aracne Bernis Lastre, Ricardo Valdés Llerena
Centro Internacional de Restauración Neurológica (CIREN)
La Habana, Cuba
________________________________________________________________________
Summary  Pain is a very common non-motor symptom in Parkinson's disease (PD), although undervalued. We analyzed the prevalence of pain, characteristics, associated factors and their impact on the quality of life and autonomy in a group of patients with PD.
The aim was to identify the incidence of pain as a non-motor complication of Parkinson's disease determining the characteristics and classification of pain in each case.
Such non-motor complications of the disease, such as pain, are unfortunately underdiagnosed and undertreated. We intend to expand the series and propose a diagnostic evaluation of pain and therapy based on improving the quality of life of our patients.
Resumen El dolor es un síntoma no motor muy frecuente en la Enfermedad de Parkinson (EP), aunque infravalorado. Analizamos la prevalencia del dolor, características, factores asociados y su repercusión sobre la calidad de vida y autonomía del paciente en una serie consecutiva de pacientes con EP.
El objetivo es caracterizar la incidencia del dolor como complicación no motora de la enfermedad de Parkinson, determinar las características y clasificación del dolor en cada caso.
Se demostró que existe una elevada prevalencia de pacientes con EP que sufren de dolor, como una de las complicaciones no motoras propias de la enfermedad y lamentablemente este síntoma queda infradiagnosticado e infratratado. Pretendemos ampliar la casuística y proponer una evaluación diagnóstica del dolor y trazar una estrategia diagnóstica y terapéutica definida inmediata en función de la mejoría la calidad de vida de nuestros pacientes.
Key words  Quality of life, pain, Parkinson's disease, non-motor symptoms of Parkinson's disease
Palabras claves  Calidad de vida, dolor, enfermedad de Parkinson, síntomas no motores de la enfermedad de Parkinson

Introduction
For many years Parkinson's disease (PD) has been described as a motor disease, characterized by clinical cardinal signs that identify it: bradikynesia, rigidity, tremor, and alteration of postural reflexes; to establish PD diagnosis, at least 3 of these symptoms are required.1
British James Parkinson described the disease for the first time and he called it "paralysis agitans"; the disease presented "involuntary movements of shaky character, with decreased muscle strength affecting the parts that are at rest and that even provoke a tendency to tilt the body forward and a way to walk with short, quick steps. The senses and the intellect remain unaltered”. This detailed definition is gathered in a treatise called "Essay on the paralysis agitans" ("An essay on the shaking palsy" in the original language), published in London in 1817.2
In addition to this core of symptoms, the disease is associated with other clinical aspects, wich can be considered motor symptoms, such as the "freezing's phenomenon" (freezing of gait), writing disorders (micrography) or facial hypomimia; in PD there are also non-motors types of symptoms that can be grouped into three main sections:
Neuropsychiatric and cognitive: depression, anxiety, psychosis, dementia, apathy, fatigue and dream disorders
Sensitive: loss of smell, paresthesia, dysesthesia, pain
Autonomic: hyperhidrosis, sialorrhea, syncope, constipation, urinary and sexual dysfunction, etc

PD has a multifactorial origin and a slowly and progressive character that mainly affects the dopaminergic neurons of the substantia nigra, which produces a depletion of dopamine from the basal ganglia.
It is currently described as a synucleinopathy, a multisystemic disease that affects a certain type of predisposed cells and that progresses in a specific way and with a topographically determined sequence. So, the components of autonomic, limbic and somatomotor systems are progressively damaged.
The involvement in PD begins at the level of the olfactory bulb nerve cells and enteric plexuses and then, ascending via the vísceromotors unmyelinated nerve fibers; then reaches the vagus dorsal nucleus and later the Central Nervous System (CNS). Thus, anatomopathological stages of involvement with their corresponding clinical correlate are established.3-5
The PD diagnosis is fundamentally clinical, and it is based on characteristic symptoms mentioned above. Nevertheless, the diagnosis of autonomic dysfunction requires an objective exploration to determine it. The early diagnosis of autonomic involvement in Parkinson's is very important because the early start of treatment helps to reduce patient morbidity and mortality.6,7

On the other hand, the involvement of the Autonomic Nervous System (ANS) is very complex, both from the anatomical and funcional point of view: it performs many useful functions, such as regulating organic functions and homeostasis's maintenance.
PD patients have an ANS' alteration, both of sympathetic and parasympathetic system
ANS' alteration in PD patients can appear in early stages of the disease, independently of whether they present clinical symptoms of dysautonomía
There is a positive correlation between the time of evolution and severity of the disease with the autonomic involvement of PD patients
Treatment with L-dopa contributes to the stabilization of ANS' functioning.

The cerebral dopaminergic circuits are key in the overtaking decisions. Dopaminergic therapy produces changes both in PD patient and in healthy controls.
As a result, the appearance of intercurrent diseases and neuropsychiatric comorbidities are frequent in these patients.8 In addition to the motor manifestations, the same pharmacological treatments imply various alterations in other areas or non-exclusive spheres of the patients' motor profile. In the disease there are sensitive and autonomic symptoms and an integral response with an interdisciplinary approach to the disease is required.9,10
PD is the second more frequent neurodegenerative disease after Alzheimer's. It is a progressive neurodegenerative disorder with accumulated effects on patients, its families and the sanitary and social systems.

In the last document published on employers'mortality in Spain, it was stood out that PD was the main cause of death in Spain in 2011, with 3274 deaths (0.8% of all deaths); A death rate adjusted by age for 100,000 people of 3.4 years; an uptrend in death rate adjusted by age between years 2001 and 2011, with increase of 21.9%.11,12
In Cuba, according to the Health Department's Statistical yearbook published in 2016, PD is one of first 35 causes of death in patients of both sexes. In 2014 there were 486 deaths, with an adjusted age-related mortality rate of 2.3 per 100,000 people and in 2015 a total of 564 deaths, with an adjusted age-adjusted mortality rate of 2.6 per 100,000 people.13
Parkinson's Disease has a negative impact on the patient's movement of everyday life. Every movement can be painful to the joints and compromize the muscular strengths; in addition, PD causes muscle rigidity, posture problems and spontaneous hyperkinetic movements. These problems are related to pain to back, arms, legs and joints.
Painful and annoying syndromes in Parkinson's disease generally occur in one of these five cases:14
1) a musculoskeletal problem connected with a bad posture, the inadequate mechanical function or physical tearing
2) pain in nerves or nervous roots, in general connected with neck or back arthritis
3) pain for dystonia, constant torsion of a group of muscles or part of the body in a forced posture
4) discomfort owed to the extreme restlessness and
5) a rare pain syndrome known as "primary pain" or "central pain" that originates from the brain.
Ability to diagnose and clinical experience to determine the cause of the pain in somebody with PD are required. The tool of more important diagnosis is the case history of the patient. Where is the pain? Where does pain radiate? When does it occur in the daytime? Does it radiate in relation to some particular activity?
Perhaps the more important task for patients with Parkinson's Disease who experience pain is to describe with great precision if their medications induce, aggravate or relieve pain.

Musculoskeletal pain
Painful joints and muscles are particularly common in the PD. Rigidity, lack of spontaneous movement, abnormalities in the posture and inadequate mechanical tensions contribute to musculoskeletal pain in Parkinson's Disease.
Rigidity shoulder, sometimes called "frozen shoulder", is one of the most common musculoskeletal complaints in PD. Pain of hip, backpain and neckpain are all common pains in the PD. With prolonged immobility of one of the extremities, band-shaped tendons, called contractures, usually on hands or feet, may occasionally develop.
An example is the contracture of hand in fist that can occur after a flexion extended of fingers. An accurate diagnosis of musculoskeletal pain is based on the careful review of case history and a physical examination that taking account of the posture, the rigidity of the extremities and the trunk, as well as the way of walking. Occasionally it can be challenging to distinguish between backpain caused by PD or by arthritis or scoliosis. Occasionally, other tests may be required: X-ray pictures, bones scanner, echography and rheumatologic or orthopedic tests. The right treatment for musculoskeletal pain in PD depends on the cause of pain. If pain stems from excessive immobility or rigidity, the doctor could prescribe dopaminergic therapy, physical therapy and exercises program. If the treatment is successfull, the patients should continue with an exercises program by focusing on range of motion exercises, to prevent the development of musculoskeletal problems in the future.

Radicular and neuropathic pain
The typical neuropathic or radicular pain syndrome in a nerve root is sciatica; it is caused by the compression or inflammation of the lumbar root L5. Patients use to describe pain as a sharp or shock that radiates to the extremities. Of course, any nerve or root is prone to nerve injury or compression. Careful neurological evaluation is required to confirm the position of the nerve and to determine the cause of the disorder. To treat root pain, pain medication (analgesics) is used, and surgery is rarely performed.15

Pain correlated with the dystonia
Dystonic spasms are among the most painful symptoms that a person with PD can experience. Pain is due to the severe movements and involuntary repetitive twisting and sustained muscle contractions, wich result in unnatural postures that the patient assumes.
Dystonia in PD can affect the extremities, trunk, neck, tongue, jaw, swallowing muscles, and vocal cords. A common form of dystonia in PD involves the feet and toes, which can twitch or twist painfully. Dystonia can also cause the arm spasm, such as a contraction of the arm behind the back, or make the head move toward the chest.
The more important step in the painful dystonia’s evaluation is to establish his relation with the medication dopaminergic.
We have to ask ourselves: is dystonia present when the drug is in its maximum effect? Dystonia appears as a strain in the initial phase, during the first effects of the drug and turns into weakness at the end of the dose?
The nature and the moment of dystonia will provide answers to these questions and will help to identify the correct treatment.The most painful dystonia appears early in the morning or when the drug's effect is in the final phase. In case of doubt, it is preferable to observe the patient for at least 7 hours to verify the relationship between the dystonia and the drug cycle. Dystonia of awakening improves with physical activity and with L-dopa. When dystonia occurs and at the end of the drug's effect, it is better to reduce the dosing intervals. In some patients, dystonia is so severe to require morphine. The patients with treatment-resistant dystonia could benefit from deep brain stimulation.
In some patients, dystonic spasms are shown as a side effect of L-dopa. In these patients it is necessary to reduce dopamine dosage, and sometimes to replace it with a less powerful agent, or add drugs for dystonia, such as amantadine.14,15

Depression and pain
We have long known that chronic pain can lead on to depression. Patients who suffer from depression frequently experience pain. People with PD have a bigger risk than the average to develop depression, wich it occurs in a 40 percent of the patients. In the assessment of pain in patients with PD  the onset of depression and its treatment should be considered.
Many patients with PD sometime experience pain during the disease. Therefore it is important that these  patients discuss the problem with their doctor. A careful revision of the history and clinical exam – including, in some cases, additional tests of diagnosis – can help to determine the cause of pain. Depending on the category of the painful symptom - musculoskeletal, neuropathic, muscular dystonic spasms, akathisia or central pain – the doctor will prescribe efficacious plan of treatment.14

Development
The non-motor effects associated with PD.16 have been known for several decades. Some of these effects occur in the early stages of the disease. In addition to the classical motor symptoms, such as tremor, rigidity and hypokinesia, in order to quantify, evaluate and set up the treatment, several symptom scales were compiled.17,18
Among non-motor symptoms, pain is often observed in parkinsonian patients and in many cases interferes with their daily routine, increasing their degree of limitation and disability and preventing a better evolution.1,14,19-21
Pain is an unpleasant sensory and emotional (subjective) experience, that all living beings with a central nervous system can experience.
As we explained earlier, based on our personal experience on the studies and the articles examined, the percentage of patients with PD who have a type of pain that is diagnosed and receive treatment is always very low. It is really, therefore, an underestimated and undertreated symptom.

Classification of pain
We can classify pain as follows:
1) Musculoskeletal pain: rigidity produced by the disease, skeletal deformity or rheumatologic origin.
2) Neuropathic radicular Pain: largely limited to the distribution area of a dermatome relating to a radiculopathy in PD patients, osteoathritis and diskal pathology, or more rarely a peripheral distribution territory determined in the case of a mono or polyneuropathy neuropathy.
3) Central neuropathic pain: burning and oppressing sensations in certain parts of the body that are often difficult to define. Not specific for PD, its have been found in other CNS diseases, as  multiple sclerosis or ictus.
4) Dystonic pain: in the extremity where the patient has dystonia, generally leg pain, but also neck and arm pain.

Diagnosis
1) Recognize if the patient has pain.
2) Identify the other PD symptoms to be able to set up a specific treatment.
 a) Characteristics of pain: appearing, localization, intensity, quality (burning, piercing, deaf, oppressive), schedule, periodicity, precipitants factors, mitigating and aggravating         circumstances.     
  b)  Framing pain in any one of different kinds.

Diagnosis of pain in Parkinson's disease (PD)
1. Detect if the patient with PD has pain
   a) Ask directly to the patient if he has pain
   b) Ask directly to the patient if he has symptoms related to sensitivity (numbness, heat, cold, etc)
   c) Submit the Brief Pain Inventory (BPI)
   d) Submit the questionnaire Study of medical results 36-item Short Form (SF-36)
2. Establish the characteristics of pain in case it is present
3. Order pain (make daily symptoms on-off and non-motors)
   a) Pain associated with PD
      • More intense in the side with more PD symptoms
      • Improvement with dopaminergic treatment
      a.1. Pause period pain
      a.2. Dystonic pain (painful dystonic spasms)
      a.3. Peak dose pain (associated with dyskinesia)
   b) Pain not directly and clearly associated with PD (a milder improvement is expected with dopaminergic treatment)
      b.1. Neuropathic root pain
      b.2. Musculoskeletal pain
4. General and neurological examination whenever the patients report pain in order to rule out any other possible cause of pain, in addition to PD.
5. Complementary explorations in selected cases
   • Lumbosacral magnetic resonance if radiculopathy is suspected
   • Magnetic cerebral resonance if the thalamic syndrome is suspected (for example, a sudden origin, to exclude the vascular cause)
   • Electromyography if polyneuropathy, radiculopathy, etc. are suspected
   • X-ray (joint pain), etc.

Study
Patients’ total of the study: 30
Painless:       7    23%
With pain:   23   76%

Classification of the pain
Neuropathic pain:           8    26%
Musculoskeletal pain:     13   43%
Disquinetic pain:            2    6.6%

Patients’ age
Less than 40 years: 1pt      3%
41-50 years: 3 pts             10%
51-60 years: 14 pts          47%
Over 61 years: 12 pts        40%

Time of evolution of the disease
Less than 5 years: 10 pts   33%
Of 6-10 years: 12 pts         40%
Of 11-20 years: 7 pts         23%
Over 21 years: 1 pts            3%

He commits burglary analogical visual of the pain
0 - 5 :  11 pts                 (47%)
6 -10:  12 pts                 (52%)
Total 23 pts

We note that out of 23 pain patients, only 10 were treated pharmacologically (43%).
With our work we found an high prevalence of pain as a non-motor complication in Parkinson's disease (23 patients out of 30 total = 76%); among the painful symptoms, the musculoskeletal one was the most widespread, with 13 patients (43%). Patients with 6 to 10 years of disease progression were 12 (40%) and aged 51-60 years were 14 (47%).
We intend to expand the case studies and propose a more detailed pain diagnostic assessment and a coordinated analgesic policy in a team of neurologists, internists, physiatrists and algologists.

Conclusions
Sensory symptoms are frequent non-motor symptoms in patients with PD. Pain is a very common and underdiagnosed symptom in PD and it is very important to identify the appropriate treatment. We intend to expand the case studies and propose a pain diagnostic evaluation to draw a therapeutic strategy based on improvement.

Conflitc of interest
The authors certify the study and the publication were conducted without conflicts of interest.

Published
27th November 2018
Bibliografia
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