Introduction: Subthalamic deep brain stimulation (STN-DBS) is a highly effective treatment for motor symptoms of Parkinson’s disease (PD). As motor symptom treatment improves, non-motor symptoms of PD are highlighted. Currently, 65-80% of PD patients suffer from chronic pain. Significant decreases are found in sensory thresholds of PD patients compared to controls. Rodent models of PD show decreased mechanical, thermal and chemical thresholds. Further, patients tested ON and OFF STN-DBS have higher thresholds while ON stimulation. STN-DBS is analgesic in a significant number of patients, reducing pain 3-6 months after surgery to tolerable levels, however the mechanism of this is unclear. It has been well established the basal ganglia play a large role in movement initiation, and recent evidence indicates it may also play a role in sensory processing. To identify the mechanism, we begin by demonstrating STN-DBS improves sensory processing in a PD rat.

Methods: Bilateral STN-DBS is implanted in rats with 6OHDA–induced parkinsonism. Sensory thresholds are tested using von-frey (VF) filaments as well as the hot plate (HPT) and tail flick (TFT) tests. We test ON and OFF high (HFS) and low (LFS) frequency stimulation to determine changes in sensory thresholds.

Results: PD rats have lower mechanical and thermal thresholds than naïve when tested using VF (bilaterally p<0.001), HPT (p=0.0117) and TFT (p=0.0132). LFS significantly improves mechanical thresholds in the left paw (p=0.028). No significant changes were found to mechanical stimuli after HFS, however the overall effect of stimulation in PD animals tended to improve (p=0.077). Finally, no changes in thermal thresholds were seen at HFS or LFS.

Conclusions: PD rats are sensitive to both thermal and mechanical stimuli. Further, our preliminary results suggest LFS modulates mechanical thresholds, but not thermal ones. HFS produced no significant effects. We acknowledge our small sample size and further investigation into STN-DBS is necessary.

Patient Care: As neuromodulation shows effective treatment of many diseases, it is important to examine the mechanism of action of these devices. Currently, many patients are already being treated with STN-DBS, which requires extensive programming and understanding of these devices. It is our hope that by examining treatment of non-motor symptoms with these same devices we could improve patient care by producing optimized settings for specific collections of symptoms, thus providing customized individual care with one single device. To do this, we must use a rodent model to examine the mechanisms by which STN-DBS affects sensory processing.

Learning Objectives: 1) Describe the important role that non-motor symptoms of PD have in the clinic, and list several non-motor symptoms. 2) Discuss in small groups the benefit of treatment of multiple modalities of PD using STN-DBS. 3) Identify a potential treatment of sensory processing deficits in PD patients.

References: 1)Fil A, Cano-de-la-Cuerda R, Munoz-Hellin E, Vela L, Ramiro-Gonzalez M, Fernandez-de-las-Penas C. Pain in Parkinson disease: A review of the literature. Parkinsonism and related disorders 2013; 19:285-294. 2)Ciampi de Andrade D, LeFaucher J, Galhardoni R, Ferreira K, Paiva A, Bor-Seng-Shu et al. Subthalamic deep brain stimulation modulates small fiber dependent sensory thresholds in Parkinson's disease. Pain 2012; 153: 1107-1113. 3) Chudler E, Lu Y. Nociceptive behavioral responses to chemical, thermal and mechanical stimulation after unilateral, intrastriatal administration of 6-hydroxydopamine. Brain Research 2008; 1213: 41-47.