Evidence-Based Treatment of Painful Diabetic Neuropathy: a Systematic Review

Curr Pain Headache Rep. 2022 Aug;26(8):583-594. doi: 10.1007/s11916-022-01061-7. Epub 2022 Jun 18.


Purpose of review: Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for evidence on conservative, pharmacological, and neuromodulation treatment options for PDN.

Recent findings: Intensive glycemic control with insulin in patients with type 1 diabetes may be associated with lower odds of distal symmetric polyneuropathy compared to patients who receive conventional insulin therapy. First-line pharmacologic therapy for PDN includes gabapentinoids (pregabalin and gabapentin) and duloxetine. Additional pharmacologic modalities that are approved by the Food and Drug Administration (FDA) but are considered second-line agents include tapentadol and 8% capsaicin patch, although studies have revealed modest treatment effects from these modalities. There is level I evidence on the use of dorsal column spinal cord stimulation (SCS) for treatment of PDN, delivering either a 10-kHz waveform or tonic waveform. In summary, this review provides an overview of treatment options for PDN. Furthermore, it provides updates on the level of evidence for SCS therapy in cases of PDN refractory to conventional medical therapy.

Keywords: Diabetes; Diabetic neuropathy; Neuromodulation; Neuropathic medications; Peripheral neuropathy; Pharmacotherapeutics.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus*
  • Diabetic Neuropathies* / therapy
  • Gabapentin / therapeutic use
  • Humans
  • Insulins* / therapeutic use
  • Pregabalin / therapeutic use
  • Spinal Cord Stimulation*


  • Insulins
  • Pregabalin
  • Gabapentin