Effect of L-DOPA on Sensory Function in vivo

Abstract

Levodopa (L-DOPA) is a compound that is used as a key medication in treating Parkinson’s disease (PD), particularly in managing bradykinetic symptoms of the disorder. Despite its nontoxicity in humans, there has been concern that high doses of L-DOPA may worsen the symptoms of peripheral neuropathy (PN) that commonly occurs in PD patients. PN is manifested in changes in peripheral sensation, weakness, and postural instability and is increasingly understood to contribute to the overall level of disability of PD patients. Here, we aimed to investigate whether high-dose L-DOPA impaired sensory function in mice. Instead of a Parkinsonian model, which is likely to cause complex changes in the skin, the unpredictable chronic mild stress (UCMS) model was used in combination with L-DOPA to assess whether L-DOPA exacerbated sensory changes caused by UCMS. In order to assess sensory function, gold-standard validated test protocols were used, including Hargreaves, tail flick, cold plantar and von Frey with a novel hot-and-cold-exploration test. The required group sizes were calculated based on pilot experiments. Our results were intriguing: mice receiving high doses of L-DOPA were more sensitive to touch and cold but less sensitive to heat. Importantly, administration of vitamin B12 prevented these sensory changes. These findings show that L-DOPA induces sensory impairments in vivo, and critically, vitamin B12 can offset these negative effects. Vitamin B12 is well known in the clinic, but controversy exists over whether it should be used with L-DOPA. Our data suggest that it should. Given that peripheral changes in sensation may contribute to overall motor impairment in PD, our data highlights the deleterious effects of L-DOPA and also the benefits of supplementing L-DOPA treatment with neuroprotective compounds like vitamin B12 to improve patient outcomes.