Subthalamic deep brain stimulation alters neuronal firing in canonical pain nuclei in a 6-hydroxydopamine lesioned rat model of Parkinson's disease

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Abstract

Introduction:

Chronic pain is one of the most common non-motor symptoms of Parkinson's disease (PD) affecting up to 85% of patients. Previous studies have established that reduced mechanical and thermal thresholds occur in both idiopathic PD patients and animal models of PD, suggesting that changes may occur in sensory processing circuits. Improvements in sensory thresholds are achieved using subthalamic nucleus (STN) deep brain stimulation (DBS), however the mechanism by which this occurs remains unresolved.

Materials and methods:

We examined unilateral medial forebrain bundle 6-hydroxydopamine (6OHDA) rat model of PD to determine whether STN DBS alters neuronal firing rates in brain areas involved in ascending and descending pain processing. Specifically, single unit in vivo recordings were conducted in the anterior cingulate cortex (ACC), the periaqueductal grey (PAG), and the ventral posteriolateral nucleus of the thalamus (VPL), before, during and after stimulation was applied to the STN at 50 or 150 Hz.

Results:

Sham and 6OHDA lesioned animals have similar neuronal firing activity in the VPL, ACC and PAG before stimulation was applied (p > 0.05). In 6OHDA lesioned rats, both low frequency stimulation (LFS) (p < 0.01) and high frequency stimulation (HFS) (p < 0.05) attenuated firing frequency in the ACC. In shams, only LFS decreased firing frequency. A subset of neurons in the PAG was significantly attenuated in both sham and 6OHDA lesioned animals during HFS and LFS (p < 0.05), while another subset of PAG neuronal activity significantly increased in 6OHDA lesioned rats during HFS (p < 0.05). Finally, low or high frequency STN DBS did not alter neuronal firing frequencies in the VPL.

Conclusions:

Our results suggest that STN DBS alters neuronal firing in descending pain circuits. We hypothesize that STN DBS attenuates excitatory projections from the ACC to the PAG in 6OHDA lesioned rats. Following this, neurons in the PAG respond by either increasing (during HFS only) or decreasing (during both LFS and HFS), which may modulate descending facilitation or inhibition at the level of the spinal cord. Future work should address specific neuronal changes in the ACC and PAG that occur in a freely moving parkinsonian animal during a pain stimulus treated with STN DBS.

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