title: Effects of subthalamic deep brain stimulation with duloxetine on mechanical and thermal thresholds in 6OHDA lesioned rats.
abstract: Chronic pain is the most common non-motor symptom of Parkinson's disease (PD) and is often overlooked. Unilateral 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesioned rats used as models for PD exhibit decreased sensory thresholds in the left hindpaw. Subthalamic deep brain stimulation (STN DBS) increases mechanical thresholds and offers improvements with chronic pain in PD patients. However, individual responses to STN high frequency stimulation (HFS) in parkinsonian rats vary with 58% showing over 100% improvement, 25% showing 30-55% improvement, and 17% showing no improvement. Here we augment STN DBS by supplementing with a serotonin-norepinephrine reuptake inhibitor commonly prescribed for pain, duloxetine. Duloxetine was administered intraperitoneally (30mg/kg) in 15 parkinsonian rats unilaterally implanted with STN stimulating electrodes in the lesioned right hemisphere. Sensory thresholds were tested using von Frey, Randall-Selitto and hot-plate tests with or without duloxetine, and stimulation to the STN at HFS (150Hz), low frequency (LFS, 50Hz), or off stimulation. With HFS or LFS alone (left paw; p=0.016; p=0.024, respectively), animals exhibited a higher mechanical thresholds stable in the three days of testing, but not with duloxetine alone (left paw; p=0.183). Interestingly, the combination of duloxetine and HFS produced significantly higher mechanical thresholds than duloxetine alone (left paw, p=0.002), HFS alone (left paw, p=0.028), or baseline levels (left paw; p<0.001). These findings show that duloxetine paired with STN HFS increases mechanical thresholds in 6-OHDA-lesioned animals more than either treatment alone. It is possible that duloxetine augments STN DBS with a central and peripheral additive effect, though a synergistic mechanism has not been excluded.
authors.affiliation: Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, United States.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Kaszuba
authors.affiliation: Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Walling
authors.affiliation: Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, United States; Department of Neurosurgery, Albany Medical Center, Albany, NY, United States.
authors.forename: Lucy E
authors.initials: LE
authors.lastname: Gee
authors.affiliation: Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, United States.
authors.forename: Damian S
authors.initials: DS
authors.lastname: Shin
authors.affiliation: Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, United States; Department of Neurosurgery, Albany Medical Center, Albany, NY, United States. Electronic address: jpilitsis@yahoo.com.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Pilitsis
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D003131:Combined Modality Therapy; D046690:Deep Brain Stimulation; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D016627:Oxidopamine; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000503:physiopathology / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000503:physiopathology; D014110:Touch
chemical_list: D000700:Analgesics; D000978:Antiparkinson Agents; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D016627:Oxidopamine; D000068736:Duloxetine Hydrochloride
keywords: Duloxetine; Hot plate test; Mechanical allodynia; Parkinson's disease; Randall-Selitto test; Subthalamic deep brain stimulation; Thermal hyperalgesia; Von Frey test