Full text
| |
| Author(s): |
Karina Henrique Binda
Total Authors: 1
|
| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2020-08-06 |
| Examining board members: |
Marucia Chacur;
Maria Ines Nogueira;
Sérgio Gomes da Silva;
Vanessa Olzon Zambelli
|
| Advisor: | Marucia Chacur |
| Abstract | |
Parkinson\'s disease (PD), the second most common neurodegenerative disease among the elderly, causing a large socioeconomic impact with increasing life expectancy of worldwide. In addition to motor alterations, there is a high prevalence of pain conditions, most often neglected, which can be responsible for worsening patients quality of life. Physical exercise, in turn, has already been described for its beneficial effects on PD, for example neuroprotection in animal models and improving the quality of life and pain threshold of patients. The aim of this project was to study the possible role of exercise on the pain threshold in a model of unilateral Parkinson\'s disease induced by 6-hydroxydopamine (6-OHDA) and the possible mechanisms involved. For this, we evaluated nociceptive (mechanical hyperalgesia) and motor behavior (cylinder test), and the expression of opioid receptors (MOR, DOR and KOR) and cannabinoids (CB1 and CB2) in regions of the nervous system involved with the pain response, they are: periaqueductal gray substance (PAG), thalamus and anterior cingulate cortex (ACC). Receptor expression was analyzed using immunohistochemistry and Western blotting techniques. In addition, autoradiography was performed to analyze synaptic density and neuroinflammation, as well as the MOR-type opioid receptor. The analyzes were performed on rats submitted to the PD model and to the treadmill exercise protocol, which was started 15 days postoperatively (PO) and performed 3x / week, for 40 minutes, for 5 weeks at a speed of 10m / min. The motor response was investigated at three moments in the study, baseline measurement (before model induction), day 7 and 49 after induction of the PD model. Nociception, on the other hand, was evaluated at 6 different moments, baseline measurement (before model induction), day 7, 14, 21, 28, 35, 42 and 49 PO. At the end of the protocol, the animals were euthanized (Day 49 PO), the brain removed and subjected to the techniques described above. Our results showed that the 6-OHDA unilateral model was successfully induced, considering that we verified death of dopaminergic cells, neuroinflammation and asymmetry in the use of the front legs. The animals in the PD model showed a decrease in the nociceptive threshold, similar to the pain in patients, and an improvement in the painful condition after the exercise protocol. Indeed, we can suggest the involvement of cannabinoid receptors type 1 and 2, opioid receptors and synaptic plasticity in the modulation of the hyperalgesic response, since we observed an increase in the levels of CB1 in PAG, an increase in the expression of CB2 in ACC and in PAG, in addition to a significant increase in the opioid receptor type MOR in the thalamus after exercise. Furthermore, there was increase of synaptic density in the striatum, substantia nigra, thalamus and hippocampus observed after the non-pharmacological intervention. Based on the results described, we can conclude that the cannabinoid and opioid receptors seem to have a predominant role, together with the modulation of synaptic density in regions involved with nociception, in the modulation of painful symptoms promoted by exercise on a treadmill. (AU) | |
| FAPESP's process: | 17/26821-1 - Effect of physical exercise on induced nociception in the Parkinson's Disease model in rats |
| Grantee: | Karina Henrique Binda |
| Support Opportunities: | Scholarships in Brazil - Master |