Introduction

The nervous system, which is your body’s central processing centre, is divided into the central and peripheral nervous systems. These divisions play designated and essential roles in coordinating bodily functions, ranging from voluntary activities to cognitive processes. When a malfunction occurs in either division, the consequences can be debilitating and often disastrous. 

Two of the conditions that can affect the central nervous system are Parkinson’s disease and Central Pain Syndrome. At first glance, these two conditions are known primarily to manifest as tremors and severe pain. This article unravels the somewhat shared pathways of Parkinson’s disease and Central Pain Syndrome, as well as the unique challenges associated with the diagnosis and treatment of both conditions.¹

What is Parkinson’s disease?

Parkinson’s disease (PD) is a progressive neurodegenerative condition characterised by problems with coordinated movements. The associated symptoms are mainly divided into motor and non-motor symptoms. However, according to the National Institute of Neurological Disorders and Stroke, the four main features of PD include: tremors, muscle stiffness (known as cogwheel rigidity), bradykinesia, and postural instability. The non-motor symptoms of PD are loss of smell, apathy, daytime sleepiness, depression, constipation, urinary incontinence, memory and concentration problems, etc. 

PD was first described by Dr James Parkinson in his medical essay titled “An Essay on the Shaking Palsy” in 1817.¹ This disease is characterised by a progressive loss or decline in the function of dopamine-producing neurons in a part of the basal ganglia called the substantia nigra.² Dopamine is an essential neurotransmitter that primarily helps to regulate movement. The depletion of dopaminergic neurons in the pars compacta of the substantia nigra causes movement issues. 

There may also be the development of Lewy bodies in the dopaminergic neurons, a pathological feature of PD.³ However, Lewy bodies are nonspecific for PD and can be found in other neurodegenerative diseases. These include progressive supranuclear palsy (PSP), dementia, multiple-system atrophy (MSA), and corticobasal degeneration (CBD).²

PD has a worldwide prevalence and no racial predilection. The prevalence of this disease ranges from 1-2 per 1000 in unselected populations.⁴ The disease also affects about 1% of older adults 60 years and above. PD occurs more in people assigned male at birth (AMAB) than in people assigned female at birth (AFAB). However, China has the most people with PD worldwide.⁵ Also, it has been estimated that by 2030, the number of PD patients in China will increase to approximately half of the world's PD population.⁶

What is central pain syndrome?

Central Pain Syndrome (CPS) is a neurological disorder that occurs due to a dysfunction of the sensory pathways of the central nervous system (CNS). The CNS includes the brain and spinal cord.⁷ Some common causes of CPS include stroke, multiple sclerosis, tumours, epilepsy, trauma in the brain or spinal cord, etc. CPS can be chronic or restricted to specific parts of the body, like the hands or feet. The severity of the pain is usually connected to the cause of the damage to the CNS.⁷ 

CPS is a neuropathic pain disorder that emanates from the CNS. This implies that there is an abnormality or damage in the pain signal pathways within the nervous system. This damage impairs the normal flow of sensory information, overactivating the pain-signalling neurons. Consequently, this leads to overstimulation of the neurons involved in the perception of pain. As a result, there is amplification of pain signals even in the absence of a direct stimulus that induces pain.⁸ 

CPS presents with a variety of symptoms. These include a burning sensation, tingling and numbness, allodynia, hyperalgesia, and emotional and significant psychological distress. Generally, CPS occurs in about 5% to 15% of people with fibromyalgia. The impact of CPS is seen more in patients with chronic back pain, which severely limits their daily activities and quality of life.⁹

Overlapping pathways in Parkinson’s disease and central pain syndrome

The main types of pain syndromes encountered in PD include central pain, peripheral pain, musculoskeletal pain, and pain caused by dystonia and akathisia.⁷ The overlapping pathways in PD and CPS include the following; 

Dysfunction of the dopaminergic neurons

The loss of dopamine-producing neurons in PD also influences CPS. This is because dopamine is involved in pain modulation, which influences the perception and dissemination of noxious stimuli. Also, the threshold of pain can be raised by dopaminergic medications used in PD, which can indirectly fuel the onset of central pain syndrome. The loss of dopaminergic neurons in the substantia nigra is followed by striatal depletion of dopamine, which excessively activates glutamate. Glutamate is an excitatory neurotransmitter implicated in the activation of chronic pain, including allodynia and hyperalgesia.¹⁰

Neuroinflammation

Neuroinflammation is a physiological response to external and internal attacks targeting the central nervous system (CNS). An acute response is typically protective, but an excessive inflammatory response can be harmful to the CNS. Both PD and CPS involve the chronic activation of a type of immune cell in the CNS called microglia. This subsequently releases pro-inflammatory cytokines such as IL-1β and TNF-α. This chronic inflammation significantly contributes to neuronal damage and oversensitisation of pain signalling pathways.¹¹

Central sensitisation

This occurs when the nervous system remains hyperactive, resulting in increased excitability of the neurons and transmission of synapses. This hyperactivity persists despite limited input from the peripheral nervous system. In this state of hyperactivity, ordinary touch produces pain (i.e., allodynia) or causes a mild stimulus to produce pain (i.e, hyperalgesia). Central sensitisation is a common phenomenon in CPS and PD, emanating from the damage to the pain signals in the nervous system and influenced by various factors seen in PD. These factors include dopamine deficiency, neuroinflammation, and protein aggregation. These contribute to the amplification of pain signals beyond what is expected in neuronal damage.¹²

Disruption of the thalamocortical pathway

The thalamus is a part of the brain that functions like a relay station, which transmits sensory information to the cerebral cortex. This is called the thalamocortical pathway. Damage to the thalamus, which could be caused by stroke, tumour, or loss of dopamine neurons seen in CPS and PD, can disrupt the thalamocortical pathway and cause exaggerated pain.¹³

Diagnostic challenges

Diagnosis of PD and CPS has been challenging due to the overlapping pathways elucidated above. A summary of the criteria for the diagnosis of both conditions is shown below:²

Treatment options

Pharmacological approaches:

• Dopamine agonists (e.g., pramipexole, apomorphine) and carbidopa-levodopa for PD¹⁴
• Anticholinergics (e.g., benztropine, ethopropazine) for tremor control¹⁴
• MAO-B inhibitors (e.g., selegiline) to preserve dopamine¹⁴
• Antidepressants, SNRIs, and anticonvulsants (e.g., amitriptyline, carbamazepine) for CPS management⁸
  

Non-pharmacological approaches:

• Deep brain stimulation (DBS): For PD patients with tremors or dyskinesia resistant to medication¹⁰
• Physical therapies: Exercise, yoga, and tai chi improve strength, balance, and musculoskeletal pain¹⁰

FAQs

Is there a cure for PD?

No, there is no cure for PD, although treatment strategies aim to improve movement issues and improve quality of life. 

What is the difference between PD and Parkinson’s syndrome?

Parkinson’s disease refers to a specific neurological condition caused by the loss of dopaminergic neurons in the basal ganglia of the brain. On the other hand, Parkinson’s syndrome is a general term for different conditions that could cause movement problems similar to those experienced in PD. 

Can PD be inherited? 

In rare cases, PD can be inherited from a family member. However, the majority of cases are idiopathic, i.e., the exact cause is not identified. 

Summary

• PD is a neurodegenerative condition primarily characterised by problems with mobility. CPS is chronic pain caused by a type of damage or injury to the central nervous system
• PD and CPS share overlapping pathways in terms of the pathophysiology. These include loss of the dopaminergic neurons, disrupted thalamocortical pathway, neuroinflammation, and central sensitisation
• Challenges with the diagnosis are based on these overlapping pathways; however, PD has four hallmark features (i.e, tremors, rigidity, bradykinesia, and postural instability), which assist with differential diagnosis
• Treatment strategies focus on the improvement of motor and non-motor symptoms associated with PD and CPS. This involves a combination of pharmacological and non-pharmacological approaches
• Pharmacological management includes the use of dopamine agonists, anticholinergics, MAO-B inhibitors, antidepressants, and SNRIs
• Non-pharmacological techniques involve deep-brain stimulation and physical therapy to improve musculoskeletal pain and mobility problems