Objective: This study aimed to investigate the role of the TRPV4 receptor in regulating the nociception in a PD model experimental for the study of non-motor symptoms.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder of the central nervous system, characterized by neurodegeneration of dopaminergic neurons. In addition, PD patients also suffer from non-motor symptoms, such as pain. A defined role for TRPV4 in PD has not been reported in the PD model for the study of non-motor symptoms

Method: We used female and male mice C57BL/6 KO for TRPV4 and female and male mice C57BL/6 wild type induced by 6 OHDA bilateral injection intro striatum. Behavioural analysis was performed at baseline and on the 7th, 14th, and  21st days after induction. The rotating cylinder test evaluated possible motor function and balance deficits. The mechanical allodynia was assessed using the Von Frey filament’s up-and-down method. Heat allodynia was assessed using the heating plate test at a constant temperature of 38º degrees (CEUA Nº 3164260423).Euthanasia and collection of samples for PCR and immunohistochemistry occurred on the 21st day after induction.

Results: Our results did not demonstrate significant differences in forced locomotion between groups on the days evaluated after PD induction, indicating the absence of substantial locomotor damage. In mechanical allodynia, when analyzing male DP WT mice, a nociceptive peak was observed on the 21st day after induction (p<0.0001). However, TRPV4 KO animals did not develop mechanical allodynia. Moreover, male PD WT mice showed differences on days 7th, 14th, and 21st  with a peak of heat allodynia on day 14th after induction compared to Sham WT mice (p<0.001)(figure 2). We did not observe heat allodynia in TRPV4 KO mice. We also observed increased expression of the TRPV4 receptor by PCR in PD WT mice (figure 3). The tyrosyl hydrolase immunohistochemistry and the cylinder test confirmed the PD model.

Conclusion: In conclusion, gene deletion of the TRPV4 receptor effectively protects the development of mechanical and heat allodynia in the bilateral 6-OHDA injection model, improving the study of nociception. The present study provides an understanding of future PD nociception research for more refined approaches to testing and treating nociception in PD models.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-nociception-in-a-model-of-parkinsons-disease-for-the-study-of-non-motor-symptoms-in-trpv4-animals/