Background & Aims
Parkinson’s disease (PD) is a neurodegenerative disorder of the central nervous system, characterized by neurodegeneration of dopaminergic neurons, causing the reduction of dopamine innervation (BLOEM et at. 2021). However, the etiology of PD remains unknown, but evidence shows that oxidative stress can play an important role in its development (JIANG et al. 2016). Considering that oxidative stress is related to physiological processes of pain, it is relevant to investigate pain in PD models (TEIXEIRA-SANTOS et al. 2020). It is crucial to highlight that the models conventionally used for PD research often present substantial motor deficits, which can compromise the accurate assessment of nociception in the animals studied (PINGALE et al. 2020). Thus, the primary purpose of this study was to standardize an experimental model of PD that enables an effective assessment of nociception, considering the specific nuances of the condition.
Methods
We used the bilateral injection model of 6-hydroxydopamine (6-OHDA) to induce a model of Parkinson’s Disease (PD), aiming to investigate non-motor symptoms. Male and female mice of the C57BL/6 strain were divided into the 6-OHDA and Sham groups. Behavioral analysis was performed at baseline and on days 7, 14, 21, and 28 after induction. According to the protocol by DE OLIVEIRA et al., 2017, the rotating cylinder test was performed to evaluate possible impairments in motor function and balance. The mechanical allodynia was assessed using Von Frey filaments of different intensities using the up-and-down method (DIXON, 1980). We used the acetone test on the plantar surface to measure cold allodynia, following the procedure of RITTER et al., 2020. The assessment of heat allodynia was conducted using the heating plate test at a constant temperature of 38º degrees, according to the protocol by TODAKA et al., 2004.
Results
In the rotating cylinder test, no significant differences were found in the groups on any of the days evaluated after induction of Parkinson’s disease, indicating the absence of locomotor damage. In the Von Frey test, when analyzing male mice, a nociceptive peak was observed on the 21st day after induction (p>0.0001), while female mice showed this peak on the 7th day after induction. In the acetone test, female DP mice manifested greater cold allodynia compared to males on the 14th day after induction (p>0.0001). In the hot plate test, DP females exhibited differences on days 14, 21 and 28, with a peak of heat allodynia on the 14th day after induction compared to Sham animals (p>0.0001). On the other hand, males with PD showed differences on the 7th, 14th, 21st and 28th days, with a peak of heat allodynia on the 14th day after induction compared to Sham animals (p>0.001).
Conclusions
In conclusion, using the bilateral 6-OHDA injection model proved effective in inducing a PD model in C57BL/6 mice, allowing the investigation of non-motor symptoms. Behavioral assessment at different time points post-induction provided a comprehensive understanding of the observed nociceptive changes. Our results contribute to a more comprehensive understanding of non-motor symptoms in PD, highlighting the importance of considering such variables in the assessment of nociception in experimental models of PD for the research and development of more personalized therapeutic strategies. The present study provides results for future research and paves the way for more refined approaches to understanding and treating PD pain.
References
JIANG, Tianfang; SUN, Qian; CHEN, Shengdi. Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease. Progress in neurobiology, v. 147, p. 1-19, 2016.
TEIXEIRA-SANTOS, Luísa; ALBINO-TEIXEIRA, António; PINHO, Dora. Neuroinflammation, oxidative stress and their interplay in neuropathic pain: Focus on specialized pro-resolving mediators and NADPH oxidase inhibitors as potential therapeutic strategies. Pharmacological Research, v. 162, p. 105280, 2020.
PINGALE, Tanvi; GUPTA, Girdhari Lal. Classic and evolving animal models in Parkinson’s disease. Pharmacology Biochemistry and Behavior, v. 199, p. 173060, 2020.
DE OLIVEIRA, Paulo Alexandre et al. Moderate traumatic brain injury increases the vulnerability to neurotoxicity induced by systemic administration of 6-hydroxydopamine in mice. Brain Research, v. 1663, p. 78-86, 2017.
DIXON, Wl J. Efficient analysis of experimental observations. Annual review of pharmacology and toxicology, v. 20, n. 1, p. 441-462, 1980.
RITTER, C., et al. Nociception in a Progressive Multiple Sclerosis model in mice is dependent on spinal TRPA1 channel activation. Mol Neurobiol, 2020.
TODAKA, Hiroshi et al. Warm temperature-sensitive transient receptor potential vanilloid 4 (TRPV4) plays an essential role in thermal hyperalgesia. Journal of Biological Chemistry, v. 279, n. 34, p. 35133-35138, 2004.
Presenting Author
Leonardo Pereira
Poster Authors
Leonardo Pereira
MSc
Federal University of Santa Maria-UFSM
Lead Author
Gabriela Trevisan dos Santos
Federal University of Santa Maria-UFSM
Lead Author
Fernanda Viero
MSc Pharmacology
Federal University of Santa Maria-UFSM
Lead Author
Caren Antoniazzi
Phd Pharmacology
Federal University of Santa Maria-UFSM
Lead Author
Sabrina Kudsi
MSc Pharmacology
Federal University of Santa Maria-UFSM
Lead Author
Helen Brito
Grad Pharmacy
Federal University of Santa Maria-UFSM
Lead Author
Topics
- Mechanisms: Biological-Molecular and Cell Biology