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Pathophysiology of Neural Circuits Underlying Pain in Prodromal to Advanced Parkinson’s Disease

Study Rationale: Many people with Parkinson’s disease (PD) suffer from pain that is not managed well by existing therapies. We believe the ineffectiveness of these treatment strategies may be due to a lack of understanding of the biological processes underlying pain that are unique to PD. In particular, some of the brainstem areas affected by PD, at very early stages before PD is diagnosed, include neural circuits that normally curb the experience of pain.  Our new results show that mice that experiences changes in the brainstem characteristic of early PD experience more pain than healthy mice.

Hypothesis: We hypothesize that because the brainstem areas responsible for curbing pain are affected in early PD, they contribute directly to the exacerbation of pain in people with PD and may even trigger pain onset.

Study Design: Our team, which includes two pain specialists and experts in PD, will demonstrate that mice exhibiting the brainstem changes that occur in very early PD experience more pain. Next, we will use cutting-edge methodologies to link changes in the activity of the precise brainstem cells that respond to pain with the development of PD pain. Finally, we will use advanced techniques from multiple scientific disciplines to show how cells in the brainstem and spinal cord that are involved in pain sensation exhibit altered activity in PD and determine how these changes worsen the experience of pain.

Impact on Diagnosis/Treatment of Parkinson’s disease: A better understanding of the biology of pain in PD can lead to the rational design of better treatments. Additionally, we believe that the pain that is experienced before individuals are diagnosed with PD has unique attributes that can facilitate earlier diagnosis in others with the condition.

Next Steps for Development: In future projects, we plan to examine whether the gold standard therapies for PD, such as administration of dopamine and deep brain stimulation, can be fine-tuned to alleviate PD pain.


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