New combined treatment approach for pain relief and reduced inflammation in people living with Parkinson’s disease

Parkinson’s disease is a neurodegenerative condition caused by the gradual loss of brain cells that produce dopamine. This is a chemical that is crucial for controlling movement and therefore, the loss of brain cells leads to reduced levels of dopamine and poor movement control. Hence, common symptoms of Parkinson’s disease include shaking at rest, muscle stiffness, and slowed movement, alongside non-motor symptoms such as constipation, sleep disturbances, low mood and cognitive impairment.

Pain is a very common yet overlooked non-motor symptom of Parkinson’s disease. According to the Parkinson’s Foundation, more than 80% of people with Parkinson’s disease report experiencing pain. This pain may arise directly from the disease itself or due to the ineffectiveness of long-term treatments. For example, levodopa is a dopamine-based treatment that aims to restore dopamine levels to improve motor function. However, after taking levodopa for some time, the effects may wear off, leading to involuntary movements that can lead to muscle fatigue and joint strain that contribute to pain. In addition, specific markers of inflammation have been found to be elevated in people with Parkinson’s disease and it is thought that chronic pain may serve as a stressor which triggers immune responses that both worsens pain and ultimately contributes to the loss of brain cells. Importantly, pain has a major impact on quality of life and mental wellbeing and so better ways to provide pain relief are urgently needed.

This study therefore aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation that uses magnetic pulses to influence the activity of specific brain regions involved in movement and pain, may be successful at providing pain relief and reducing inflammation in people with Parkinson’s disease. Of note, rTMS is already being used in clinical practice for the treatment of conditions such as depression. Similarly, this study examined the extent to which the drug entacapone, which helps levodopa to work more consistently overtime by slowing its breakdown, may also provide pain relief when combined with just levodopa or together with levodopa and rTMS.

Why is the study important?

Pain can be just as debilitating as movement problems in Parkinson’s disease. While many current treatments aim to restore motor function, pain continues to severely affect the daily life of people living with this disease. This study focuses on pain as a key symptom of Parkinson’s disease and tests a combined treatment approach that could offer a more holistic way to manage the condition. Additionally, this study suggests a biological explanation for pain, by linking pain to specific inflammatory markers, which is important for identifying new and effective therapies.

What did the authors do and how did they do it?

A total of 72 patients with Parkinson’s disease were enrolled in this study and randomly assigned to three groups: Group 1 received levodopa and a mock form of brain stimulation (placebo), Group 2 received levodopa, entacapone and the placebo, and Group 3 received levodopa, entacapone and rTMS. These 72 participants were selected since they experienced moderate to severe pain and had been treated exclusively with levodopa for at least 3 months before entering the study.

The interventions lasted for 24 weeks, with both rTMS and the placebo delivered 3 times per week. A 6-month follow-up period was also chosen to assess the sustained clinical benefit of treatment, although, longer-term studies are still needed as 6 months may not be enough time. After treatment, the patients were asked to rate the intensity of their pain and overall quality of life, as well as depressive symptoms and motor function, using standard clinical rating scales. Additionally, specific inflammatory markers were measured to determine if pain relief was accompanied by reduced inflammation.

What are the results?

After six months, significant improvements in pain, mood, motor function, and overall quality of life were evident across all groups. Participants receiving levodopa and entacapone experienced greater improvements than those just receiving levodopa, while the largest overall benefits were seen in Group 3 (levodopa, entacapone and rTMS).

While some participants in Group 3 reported mild scalp discomfort or headache during the rTMS sessions, this treatment was generally well-tolerated. Levels of the inflammatory markers also decreased across all groups, with the greatest reductions also observed in Group 3. While these findings suggest pain relief is associated with reduced inflammation, the researchers state that this finding provides indirect support for a causal relationship. Nonetheless, these findings suggest that treating Parkinson’s disease-related pain using a combination approach may be more effective than medication alone, and that pain is likely influenced by changes in brain activity and inflammatory processes as well as dopamine loss.

What do the findings mean going forward for people with the disease?

The results highlight a novel holistic way to manage pain, particularly for those whose pain is not controlled well by standard medication. The results of this study suggest that rTMS may be a valuable add-on therapy for managing pain and potentially other non-motor symptoms. They also emphasise the link between reduced pain and lower levels of inflammation, opening new avenues for therapeutic approaches. However, larger and longer-term studies are needed before rTMS can be widely recommended as a treatment for Parkinson’s disease, to confirm its effectiveness and identify which patients are most likely to benefit. Overall, the study supports a more holistic approach to Parkinson’s disease treatment that goes beyond treating motor symptoms alone and aims to improve everyday functioning and wellbeing.

This study can be found at
https://doi.org/10.1016/j.brainresbull.2025.111652

Lead Authors
Yang., Y & Liu., H

Publication details including date of publication
This paper was published in the Elsevier Brain Research Bulletin (Volume 233, Article 111652) in December 2025 and first published online on 23rd November 2025.