Abstract
Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson’s disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, l-DOPA (l-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating l-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson’s disease to a hind paw-induced persistent inflammation. Further, the effect of l-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by l-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. l-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of l-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.
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Acknowledgements
We would like to thank Célia Aparecida da Silva for the technical support. The equipment and drugs used in this work were acquired from FAPESP, CNPq, CAPES, Brazil. The experiments presented in this manuscript comply with the current Brazilian laws. This manuscript was revised by Elsevier Language Editing Services (Elsevier Webshop).
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The experiments were performed in compliance with the recommendations of SBNeC (Brazilian Society of Neuroscience and Behavior), which are based on the US National Institutes of Health Guide for Care and Use of Laboratory Animals. The local Ethical Committee approved the protocol.
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Nascimento, G.C., Bariotto-dos-Santos, K., Leite-Panissi, C.R.A. et al. Nociceptive Response to l-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats. Neurotox Res 34, 799–807 (2018). https://doi.org/10.1007/s12640-018-9896-0
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DOI: https://doi.org/10.1007/s12640-018-9896-0