The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA‐lesioned rats

Abstract

Chronic pain is a major complaint for up to 85% of Parkinson Disease patients, however, often not identified as a symptom of Parkinson’s disease. Adequate treatment of motor symptoms often provides analgesic effects in Parkinson’s patients, how this occurs remains unclear. Studies have shown both Parkinson’s patients and 6-hydroxydopamine lesioned rats exhibit decreased sensory thresholds. In humans, some show improvements in these deficits after subthalamic deep brain stimulation, while others report no change. Differing methods of testing and response criteria may explain these varying results. We examined this effect in 6-hydroxydopamine lesioned rats. Sprague dawley rats were unilaterally implanted with subthalamic stimulating electrodes in the lesioned right hemisphere and sensory thresholds were tested using vonFrey, tail flick and hot plate tests. Tests were done during and off subthalamic stimulation at 50 and 150Hz to assess its effects on sensory thresholds. 6-hydroxydopamine lesioned animals exhibited lower mechanical (left paw, p<0.01) and thermal thresholds than shams (hot plate, p<0.05). Both 50 and 150Hz increased mechanical (left paw; p<0.01) and thermal thresholds in 6-hydroxydopamine lesioned rats (HPT; 150Hz, p<0.05, 50Hz, p<0.01). Interestingly, the magnitude of improvement in mechanical thresholds during LFS was similar between animals, whereas during HFS was much more diverse. This study shows that subthalamic deep brain stimulation improves mechanical allodynia and thermal hyperalgesia in 6-hydroxydopamine lesioned animals at both high and low frequencies. Furthermore, we suggest considering using low frequency stimulation when treating Parkinson’s patients where pain remains the predominant complaint.

Reversal of hyperactive subthalamic circuits differentially mitigates pain hypersensitivity phenotypes in parkinsonian mice

“…In the present study, we observed that unilateral lesion of SNc DA neurons reduced nociceptive thresholds bilaterally in mice, similar to previous findings in unilateral 6-OHDA lesioned rats (49)(50)(51). Significant bilateral pain symptoms have also been reported in PD patients with unilateral motor deficits (52,53).…”

Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

“…26,37,53 Moreover, a recent study in 6OHDA (6-hydroxydopamine)-lesioned rats has suggested that both HFS and low-frequency stimulation (LFS) of the STN increase mechanical and thermal thresholds. 24 Thus, this work implies that pain may be modulated with LFS of the STN. Additionally, STN LFS has been shown to improve motor function in PD patients.…”

The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson’s Disease Patients

“…Our preclinical data has shown that STN DBS modulates neuronal firing in the ACC in 6OHDA lesioned rats but not shams, while responses in the PAG (medial pain pathway) and VPL (lateral pain pathway) are similar between control and parkinsonian rats . Although we did not explore whether STN DBS could modulate neuronal firing frequencies in the ACC and PAG during acute pain stimulus, we hypothesize that pain perception in PD patients and the mechanism by which DBS can alter thermal and mechanical thresholds may be mediated by top‐down cortical control of descending inhibitory pain pathways.…”

“…The emotional and affective component of pain, specifically from the ACC, is thought to be highly important to the development of pain symptomology in PD patients . Preclinical work by our group has demonstrated that STN DBS modulates neuronal firing in the ACC in 6OHDA lesioned rats but not shams, while responses in the periaqueductal gray (PAG) and ventral posteriolateral nucleus (VPL) are similar between control and parkinsonian rats . Here, to better understand the role of the basal ganglia (BG) in PD relative to pain processing, we examine how LFPs and SUAs change with exposure to mechanical and thermal stimuli at sensory detection and pain thresholds in the STN, Gpe, and Gpi.…”