67: Evaluation of Nociception in Trpv4?/? Mice in a Parkinson�s Disease Model

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Assessment and Measurement of Pain/Nociception, Animal imaging (includes Ca2+ imaging, fluorescence microscopy), Behavioral studies

Background and Aims: Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system, characterized by progressive loss of dopaminergic neurons, particularly in the substantia nigra, leading to classic motor symptoms. In addition, PD patients also suffer from a wide range of non-motor symptoms, including pain, which markedly impact quality of life. Although TRPV4 has been implicated in nociceptive processing and neuroinflammatory mechanisms, the role of this channel in PD, especially in models of non-motor symptoms, remains unclear. Therefore, this study aimed to investigate the role of the TRPV4 receptor in regulating nociception in an experimental PD model assessing non-motor symptoms.

Methods: We used female and male C57BL/6 TRPV4 knockout mice and wild-type C57BL/6 mice subjected to bilateral 6‑OHDA injection into the striatum. Behavioral analysis was performed at baseline and on the 7th, 14th, and 21st days after induction. The rotating cylinder test and open field were used to evaluate motor function and balance. Mechanical allodynia was assessed using the Von Frey up‑and‑down method, and heat allodynia using the hot plate test at 38ºC. Euthanasia and tissue collection for PCR and immunohistochemistry occurred on day 21 after induction.

Results: Our results did not demonstrate significant differences in forced locomotion or total distance travelled between groups after PD induction, indicating absence of marked locomotor damage. In mechanical allodynia, male PD WT mice showed a nociceptive peak on day 21 (p<0.0001), whereas TRPV4 KO animals did not develop mechanical allodynia. Male PD WT mice also displayed heat allodynia on days 14, and 21, compared to Sham WT (p<0.001), which was not observed in TRPV4 KO mice. We additionally detected increased TRPV4 expression by PCR in PD WT mice. Tyrosine hydroxylase immunohistochemistry and the cylinder test confirmed the PD model.

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

References: Deenadayalu, A., & Paramanandam, V. (2022, September). TRPV4 Mutation related Parkinson’s Disease with Scapuloperoneal spinal muscular atrophy. In MOVEMENT DISORDERS (Vol. 37, pp. S558-S558). 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY.
Masini, D., Plewnia, C., Bertho, M., Scalbert, N., Caggiano, V., & Fisone, G. (2021). A guide to the generation of a 6-hydroxydopamine mouse model of Parkinson’s disease for the study of non-motor symptoms. Biomedicines, 9(6), 598.

Presenting Author: Leonardo Gomes Pereira
Submitting Author: Leonardo Gomes Pereira

Senior Author: Leonardo Gomes Pereira

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Caren Tatiane de David Antoniazzi: PhD - Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC, Canada
• Romina Nassini: Professor - Department of Health Sciences, University of Florence, Florence, Italy
• Gabriela Trevisan: Professor - Department of Pharmacology and Physiology, Federal University of Santa Maria1, Santa Maria, RS, Brazil