Parkinson's Disease: Pain Management, Challenges and Solutionsby Prof. Gianliuca Egidi, Pescara 🇮🇹

Parkinson's Disease: Pain Management, Challenges and Solutions - by Prof. Gianliuca Egidi, Pescara 🇮🇹

Parkinson's Disease: Pain Management, Challenges and Solutions

Pain Treatment in Parkinson's Disease Patients: Challenges and Solutions.

This article focuses on the diagnosis and management of Parkinson's-related pain which is one of the most frequent non-motor symptoms in Parkinson's disease, which is the second most common neurodegenerative disease after Alzheimer's disease. Pain is classified by patients as an annoying symptom at all stages of the disease. In the early stage of Parkinson's disease, pain is judged to be the most annoying symptom. Knowledge of the correct diagnosis of the origin of pain and the possible treatment methods for pain relief is of great importance. Symptoms have a major negative impact on health-related quality of life.

Distinguishing PD-related pain from pain of other origins is a major challenge and could be characterized by 'some symptoms under the same umbrella'. Among the different forms of pain related to Parkinson's disease, musculoskeletal pain is the most common form, accounting for 40-90% of the pain reported in patients with Parkinson's disease. An increase due to pathophysiological pathways other than those secondary to stiffness, tremor or any other motor manifestation of the disease seems more likely.

In Parkinson's disease, the basal ganglia manage somatosensory information differently and in patients with Parkinson's disease an increased sensitivity to subjective pain with a lower electrical and thermal pain threshold is reported. The mechanism is assumed to be a decrease in activity of the descending inhibitory control system of the basal ganglia. The pain of Parkinson's disease, like some non-motor symptoms, remains underdiagnosed and, therefore, poorly managed. A systematic collection of patient descriptions regarding the type, quality and duration of pain is therefore of utmost importance.

Recent studies have validated new and more specific dedicated pain scales for symptoms related to Parkinson's disease. Symptomatic treatments based on the clinical classification of pain include pharmacological and non-pharmacological methods, and in part, invasive approaches. In the clinic, pharmacological and interventions may not be effective at various levels - in single or combination therapy - and should be employed, as therapeutic strategies to manage the pain of Parkinson's disease have not been validated to date.

Multimodal approaches should always be taken into consideration, dopaminergic therapies should be modified, analgesics and antidepressants should be considered, including the use of different forms of complementary therapies.


James Parkinson described the phenomenon of pain in Parkinson's Disease in 1817 in his original work "An Essay on Shaking Paralysis":

[...] the writer was called by a woman of about 40, for a great pain in both arms, which extended from the shoulders to the fingertips. She stated, that […] she had not found any benefit from any medicine used […] which left both arms and hands in a very weak and shaking state.

Now, nearly 200 years later, the stressful and frequent chronic pain related to Parkinson's disease remains an underestimated and underdiagnosed symptom in Parkinson's disease.

Parkinson's disease incidence and prevalence, general and Parkinson's disease-related pain

Estimates of the incidence and prevalence of Parkinson's disease have provided conflicting data. In Europe, the annual incidence is estimated between 5/100000 and 346/100000. Approximately 60,000 Americans are diagnosed with Parkinson's disease each year. The challenges involved in differential diagnosis and other forms of Parkinsonism, as well as the long time elapsed between the onset of symptoms similar to Parkinson's disease and the correct diagnosis, are often responsible for the discrepancy in the numbers.

The reported prevalence of Parkinson's disease pain and Parkinson's disease-related pain varies across studies. In 2008, Negre-Pages et al estimated a prevalence of chronic pain in Parkinson's disease to be over 60%.

Parkinson's disease pain is often reported as heterogeneous in its clinical presentations, with a disabling effect on quality of life assessment. In 1998, the Swedish Parkinson Association reported a survey of non-motor symptoms that included nearly 1,000 people with Parkinson's disease, revealing that pain was more common in females than males (54% and 45% respectively). However, general pain is also common in the population, around 18-19% in the general adult population according to prevalence data.

In the early stages of Parkinson's disease, pain is considered to be one of the most annoying non-motor symptoms, and appears to affect the side of the body initially affected by the motor symptoms of the disease. (Table 1)


1 SLOWNESS 33 5 13

2 TREMOR 30 9 4

3 RIGIDITY 6 26 11

4 PAIN 10 10 5


6 MOOD 4 6 4

7 GRAPH 2 3 6


9 SLEEP 2 4 1


Tab. 1: Ranking of the ten most troublesome symptoms related to PD in 92 patients with early onset disease lasting over 6 years (data obtained by Politis et al.)

Pathophysiological pathways of pain in Parkinson's disease

The origin of pain in Parkinson's disease remains poorly understood. Sometimes, it appears as dystonia when the dopaminergic effects wear off. The pathophysiological mechanism most likely behind this phenomenon is the interaction of dopamine in the system of other monoamines such as norepinephrine and serotonin, through both the inhibitory and excitatory pathways. Abnormalities in the descending pathway affect the processing of central pain. Furthermore, patients with Parkinson's disease describe clinically recognized neuropathic pain and other sensations of muscle pain. This led to the exploration of pathways other than those secondary to rigidity, tremor or any other motor manifestation of the disease, such as an abnormal processing of nociception in patients with Parkinson's disease suffering from pain as the most likely suspect. The basal ganglia process somatosensory information in different ways, and an increased sensitivity to subjective pain with lower electrical and thermal thresholds has been reported in patients with Parkinson's disease. This anomalous processing also includes disorders related to Parkinson's disease such as multiple systemic atrophy, which shows almost the same prevalence of pain in Parkinson's disease.

The anatomical-functional arrangement of the basal ganglia is characterized by multiple interconnected structures and systems. The basal ganglia act as an integration point for afferent fibers in the organization of behavioral responses to stimuli. The influence coming from the cortical and subcortical regions contributes to the system between the thalamus, cortex and basal ganglia. The cortical areas involved play an important role in the processing and modulation of pain. These territories include the frontal and parietal lobes, the insula and the hippocampus. Electrical stimulation of the substantia nigra, one of the basal ganglia nuclei, modulates pain from the dorsal horns of the spinal cord, which is likely mediated by a descending dopaminergic inhibitory pathway originating from the midbrain.

The two main dopaminergic pathways are well known. The nigrostriatal dopaminergic pathway projects from the substantia nigra to the striatal dorsal structures of the corpus striatum. This path has an established function in sensory-motor integration and control. The structures, such as the amygdala, the thalamus and the nucleus accumbens, are reached by neurons originating in the ventral tegmental area. Different projections from the ventral tegmental area also innervate specific cortical regions, such as the motor cortex and the prefrontal cortex. Consequently, there is a significant overlap between the dopaminergic system and the aforementioned brain regions involved in pain processing, and interference in dopaminergic concentrations in these areas could lead to motor and sensory disturbances.

Much evidence suggests that other areas such as brainstem nuclei and diencephalic structures are affected, as do extrabrain structures, spinal cord, and autonomic enteric plexus. Furthermore, as dopaminergic drugs may be effective for various non-motor symptoms, including pain in Parkinson's disease, evidence suggests that these symptoms are associated with dopaminergic denervation in brain areas not primarily related to motor symptoms.

Physiological ways of pain relief

In the early 1960s, the theories initially developed by Melzack and Wall were introduced. These proposed three aspects of afferent input approved for pain: the continuous activity that precedes the stimulus, the activity of the evolving stimulus, the relative balance of activity in the large versus small fibers. The concept of the "Gate Control Theory" was introduced. Painful messages encounter "nerve gates" in the spinal cord that open and close depending on a number of factors (possibly including instructions from the brain). When the gates are open, the painful message "passes" more easily and the pain can be intense. When the gates are closed, the painful message is not conveyed to the brain and may not be proven. Although the details of this process remain poorly understood, it can help explain why various treatments are effective.

The existence of low-threshold mechanoceptive C tactile afferents was initially described by Vallbo et al. These afferents comprise a second anatomically and functionally distinct system that signals touch in humans. The activation of these fibers is more closely related to limbic functions rather than cognitive and motor functions. Although a quick, accurate and information-rich A beta touch intensely reflects the outside world through skin events in an exteroceptive manner, the activation of tactile C fibers shares more characteristics with the intraceptive modalities. This slow, affective nature seems involved in maintaining physical well-being.


Pain, stress and stress biomarkers

Stress and pain are often closely linked. One affects the other, creating a vicious circle that lays the foundation for chronic pain and chronic stress. Therefore, stress management should be a component of pain therapy.

The Merriam-Webster Encyclopedia defines the term stress as a "physical, chemical, or emotional factor that causes physical or mental tension and may be a causative factor of illness." The effect of stress can be explained as a physical or mental tension due to factors that tend to alter an existing balance.

In humans, stress is often a reaction to difficulty and possibly dangerous situations. The search for humoral substrates that reflect physical experiences of stress is an area of ​​attractive scientific curiosity. The "fight or flight" response occurs when a person anticipates a threat and the body uses energy to fight or flee far "to live another day". This response is characterized by the release of epinephrine from the adrenal glands, which causes vasoconstriction and increased heart rate.

Measurements of cortisol concentration in saliva have been shown to be a simple and useful indirect biomarker of stress. From the study of the function of the hypothalamus-pituitary-adrenal axis and of cortisol secretion in patients with Parkinson's disease as a surrogate marker of stress and indirect pain, it is possible to study and objectify the effects of the intervention with the aim of providing relief. to stress / pain. Other biomarkers are the concentrations of epinephrine, norepinephrine and oxytocin. Blood pressure and heart and respiratory rates are examples of other markers for assessing stress reduction.

Examples of pain scales

Visual analog scale

The visual analog scale measures a continuum of chosen characteristics present. For example, the pain perceived by the patient extends over a continuum from painlessness to extreme pain intensity. This range of perceived pain appears continuous to the patient. Pain is not reported on an ordinary scale with jumps between values ​​such as fair, moderate and severe. Descriptive words are shown only on both terminus, usually on a line 100 mm long. This assessment is very subjective and best used on single individuals rather than on groups of individuals simultaneously. Many experts claim that VAS can produce serial data at best. This is important to consider in the statistical analysis of VAS data. A ranking in order of score rather than exact values ​​may be the best way to manage patient records on the 100 mm line.

Brief Pain Inventory

The Brief Pain Inventory was initially created with the aim of measuring pain in cancer patients. It measures pain relief, pain quality and understanding of the cause of pain in terms of pain intensity (sensory dimension) and pain interference (reactive dimension).

Examples of pain scales in Parkinson's disease


This is a pain self-assessment tool developed with the aim of improving pain assessment and management of patients with acute and chronic pain, not exclusively for Parkinson's disease pain. It is a rigid, white, plastic tool. Two methods of pain assessment are located on the Pain-O-Meter (POM). The first is a 10 cm VAS scale with a movable marker that patients use to assess their pain. The second is a list of 15 sensory and 11 affective descriptive words. Each descriptive word is assigned to an intensity value that can range from low (1) to high (5).

King's PD Pain Scale

To date, there is no specific validated scale that is widely used in the area of ​​pain related to Parkinson's disease (Parkinson's disease pain). Therefore, it is important to describe the context of the study in this field. The King's PD Pain Scale was unveiled very recently. The scale is simple to administer, requiring the examiner to ask the patient 14 questions and calculate the severity and frequency of pain in Parkinson's disease. The time required for the caregiver and the patient is estimated to be around 10-15 minutes. Data from seven domains provide information on the different types of pain in Parkinson's disease, broadly classified as a nociceptive and neuropathic pattern. Precisely, the scale captures pain from that connected to time linked to the disappearance of the effects of antiparkinsonian drugs, that is, to pain connected to the end of pharmacological effects, to central, orofacial and radicular pain.

Clinical diagnosis of pain related to Parkinson's disease


Traditionally, pain in Parkinson's disease is classified into 5 domains: musculoskeletal, radicular / neuropathic, related to dystonia, akathisia and central. The most common pain syndromes are musculoskeletal and dystonic ones. The central pain of Parkinson's disease is the least common, but important to recognize; it can be intermittent or persistent on its own and is often described by patients as widespread pain, burning or cramping. There need not be any lesions in the peripheral nervous system. Different parts of the body can be affected and autonomic symptoms are often combined. There are no unusual descriptions of pain from facial, abdominal or genital locations.

However, the definition of central pain is not specific and the term is often confused with central neuropathic pain which has another definition. The central mechanisms are almost always involved in the pain syndromes of Parkinson's disease, but this is not the same as meeting the criteria for central neuropathic pain. (Figure 1)

Figure 1: Simplified diagram of pain assessment and its origin in PD

Clinical decisions

When patients with Parkinson's disease express painful symptoms, doctors should first determine if the pain is related to Parkinson's disease. The associations between painful sensations and on / off symptoms are crucial for determining the origin of pain and can support the use of dopamine substitutes to achieve pain relief. How the patient is evaluated is also crucial, since depression and anxiety require specific treatment options. However, the relationship between depression, chronic pain and Parkinson's disease remains unclear.

La depressione potrebbe essere secondaria al dolore della Malattia di Parkinso