|Support type:||Scholarships in Brazil - Scientific Initiation|
|Effective date (Start):||June 01, 2020|
|Effective date (End):||May 31, 2021|
|Field of knowledge:||Biological Sciences - Physiology - Physiology of Organs and Systems|
|Principal Investigator:||Rosana de Lima Pagano|
|Grantee:||Karolina Vieira Lima|
|Home Institution:||Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil|
Parkinson's disease (PD) is a complex neurodegenerative disease that causes progressive dysfunction of dopaminergic and non-dopaminergic neurons, causing motor and non-motor symptoms. Among nonmotor symptoms, pain is one of the most prevalent symptoms, contributing to the deterioration of quality of life of these patients. The treatment of PD is eminently symptomatic and begins with an effective pharmacological approach that loses its effect over time, generating several complications. In this phase, the gold standard of treatment is the Deep Brain Stimulation (DBS) of the subthalamic nucleus (NST), which has clear benefits in relation to the motor and non-motor symptoms of PD. It was observed by our group that DBS-NST induces evident motor improvement and reduces hypernociception in hemiparkinsonian rats, a response accompanied by reversal of dopaminergic motor neuroinflammation and reversal of neuronal and glial hyperactivation in the posterior spinal cord (CPME). Knowing the importance of dopamine and noradrenaline in controlling nociceptive response, in this project we will investigate the effect of DBS-NST on the catecholaminergic system involved with the analgesic pathway in hemiparkinsonian rats. Therefore, we will investigate the expression of tyrosine hydroxylase (TH) enzyme in the ventral tegmental area, amygdala, hippocampus, hypothalamus and locus ceruleus. In addition, we will evaluate the double labeling of TH and dopamine-2-hydroxylase enzymes in CPME. We hypothesized that DBS is capable of modulating limbic areas, activating the descending analgesic pathway and the spinal inhibitory system by modulating catecholaminergic deficit. With this work we intend to elucidate part of the mechanism of action of DBS, focusing on the analgesic response, in order to guide the improvement of more effective therapeutic interventions for PD patients.