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Background  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 .    Methods  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.    Results  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).    Conclusions  We demonstrated a delayed effect of  HF ‐ SCS  on mechanical hypersensitivity in chronic  PDPN  animals compared with  LF ‐, or  CON ‐ SCS .    Significance  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 .

Spinal cord stimulation in experimental chronic painful diabetic polyneuropathy: Delayed effect of High‐frequency stimulation