Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy

Abstract

Objective: To investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN).

Methods: Patients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure.

Results: After the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS.

Conclusion: Five daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.

Keywords: Chronic pain; Diabetic neuropathy; Transcranial direct current stimulation.

Fig. 1

Patient flow diagram. Twelve patients withdrew from the study: seven had early discharge during stimulation sessions and five withdrew after the third session of stimulation because of poor cooperation (n=4) or headache (n=1). PDPN, painful diabetic polyneuropathy; BDI, Beck Depression Index; MMSE, Mini-Mental State Examination; VAS, visual analog scale; PT, pain threshold; CGI, Clinical Global Impression; tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, dorsolateral prefrontal cortex.

Fig. 2

Anodal tDCS. The anode was positioned over the M1 or DLPFC and the cathode over the contralateral supraorbital region (2 mA for 20 minutes on 5 consecutive days). tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, dorsolateral prefrontal cortex.

Fig. 3

After 5 consecutive days of tDCS sessions over M1, pain reduction was significantly greater compared with the sham and DLPFC groups (^***p<0.001) and compared with the sham group, its analgesic effect was sustained after 2 weeks (^***p<0.001) and 4 weeks (^**p<0.01) of follow-up. Likewise, the M1 group showed greater pain reduction than the DLPFC group (^**p<0.01) after 2 weeks. tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, left dorsolateral prefrontal cortex; VAS, visual analog scale.

Fig. 4

After 5 consecutive days of tDCS sessions, the M1 group exhibited a significantly greater reduction in CGI score (^***p<0.001), which was decreased significantly after 2 and 4 weeks of follow-up compared with the sham group (^*p=0.02, ^**p=0.008). CGI is rated on a 7-point scale: 1, normal, not ill at all; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; 7, most severely ill. tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, left dorsolateral prefrontal cortex; CGI, Clinical Global Impression.

Fig. 5

After 5 consecutive days of tDCS sessions, the M1 group exhibited a significantly greater increase in pain threshold compared with the sham and DLPFC groups (^***p<0.001). tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, left dorsolateral prefrontal cortex.