title: Spinal cord stimulation in experimental chronic painful diabetic polyneuropathy: Delayed effect of High-frequency stimulation.
abstract: Spinal cord stimulation (SCS) has been shown to provide pain relief in painful diabetic polyneuropathy (PDPN). As the vasculature system plays a great role in the pathophysiology of PDPN, a potential beneficial side-effect of SCS is peripheral vasodilation, with high frequency (HF) SCS in particular. We hypothesize that HF-SCS (500 Hz), compared with conventional (CON) or low frequency (LF)-SCS will result in increased alleviation of mechanical hypersensitivity in chronic experimental PDPN.
  
  
  
  Diabetes was induced in 8-week-old female Sprague-Dawley rats with an intraperitoneal injection of 65 mg/kg of streptozotocin (n = 44). Rats with a significant decrease in mechanical withdrawal response to von Frey filaments over a period of 20 weeks were implanted with SCS electrodes (n = 18). Rats were assigned to a cross-over design with a random order of LF-, CON-, HF- and sham SCS and mechanical withdrawal thresholds were assessed with von Frey testing.
  
  
  
  Compared with sham treatment, the average 50% WT score for 5 Hz was 4.88 g higher during stimulation (p = 0.156), and 1.77 g higher post-stimulation (p = 0.008). CON-SCS resulted in 50% WT scores 5.7 g, and 2.51 g higher during (p = 0.064) and after stimulation (p < 0.004), respectively. HF-SCS started out with an average difference in 50% WT score compared with sham of 1.87 g during stimulation (p = 0.279), and subsequently the steepest rise to a difference of 5.47 g post-stimulation (p < 0.001).
  
  
  
  We demonstrated a delayed effect of HF-SCS on mechanical hypersensitivity in chronic PDPN animals compared with LF-, or CON-SCS.
  
  
  
  This study evaluates the effect of SCS frequency (5-500 Hz) on mechanical hypersensitivity in the chronic phase of experimental PDPN. High frequency (500 Hz) - SCS resulted in a delayed effect- on pain-related behavioural outcome in chronic PDPN.
authors.affiliation: Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, The Netherlands.|Pain Management and Research Center, Department of Anesthesiology, MUMC+, Maastricht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Beek
authors.affiliation: Pain Management and Research Center, Department of Anesthesiology, MUMC+, Maastricht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Kleef
authors.affiliation: Pain Management and Research Center, Department of Anesthesiology, MUMC+, Maastricht, The Netherlands.|Department of Clinical Neuroscience, (Functional Neurosurgery), Karolinska Institutet, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Linderoth
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), MUMC+, Maastricht, The Netherlands.
authors.forename: S M J
authors.initials: SM
authors.lastname: van Kuijk
authors.affiliation: Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, The Netherlands.
authors.forename: W M
authors.initials: WM
authors.lastname: Honig
authors.affiliation: Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, The Netherlands.|Pain Management and Research Center, Department of Anesthesiology, MUMC+, Maastricht, The Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: Joosten
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000503:physiopathology*; D062187:Spinal Cord Stimulation / Q000379:methods*