Objective: This study investigated the role of the TRPV4 receptor in nociceptive regulation using an experimental model of Parkinson’s disease (PD) focused on non-motor manifestations.

Background: Although PD is classically defined by motor dysfunction, patients frequently present non-motor symptoms such as pain. Conventional PD models often produce marked motor deficits that may interfere with nociceptive evaluation. Recent evidence suggests TRPV4 may contribute to pain modulation in PD.

Method: Female and male C57BL/6 wild-type and TRPV4 knockout mice underwent bilateral intrastriatal 6-OHDA injections. Behavioral assessments were performed at baseline and on days 7, 14, and 21 post-induction. Motor performance was evaluated using rotarod and cylinder tests. Mechanical allodynia was assessed by the von Frey up-down method and thermal sensitivity by the hot plate test (38°C). On day 21, animals were euthanized for PCR and immunohistochemical analyses.

Results: The results showed no significant differences in forced locomotion among the experimental groups at the analyzed time points, indicating that the model did not produce substantial locomotor impairment. In wild-type PD animals, the peak of mechanical allodynia differed according to sex, occurring on day 21 in males and day 7 in females. In contrast, TRPV4 knockout mice did not develop mechanical allodynia. Wild-type male and female PD mice also showed altered thermal nociception on days 14, 21, and 28, with maximal heat allodynia observed on day 14 compared with sham wild-type animals. No heat allodynia was detected in TRPV4-deficient mice. In addition, PCR analysis revealed increased TRPV4 expression in wild-type PD animals, while tyrosine hydroxylase immunohistochemistry and cylinder test performance confirmed the effectiveness of the PD model.

Conclusion: Overall, deletion of the TRPV4 gene was associated with protection against the development of both mechanical and heat allodynia in the bilateral 6-OHDA model. The behavioral analyses performed across different post-induction time points provided relevant information about nociceptive changes in this PD model. These findings strengthen the understanding of TRPV4 involvement in PD-related pain and may support future studies aimed at improving strategies for investigating and treating nociceptive dysfunction in Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-trpv4-deletion-on-nociception-in-an-experimental-model-of-parkinsons-disease-non-motor-symptoms/