Background: Knowledge about placebo as a psychological phenomenon is not new, the use and misuse of placebo in practice and research had been demonstrated in its role for treating patients with most ‘difficult- o-treat’ conditions such as chronic pain syndromes and neuropathic pain. Objective: To evaluate the placebo-controlled trials in order to explore the placebo-related responses among patients with Diabetic peripheral neuropathy (DPN). Methods:A systematic review was performed using search terms “diabetic neuropathy, placebo/sham” in PubMed, CINAHL and Google Scholar to identify relevant studies.Descriptive data extraction and synthesis was done to organize studies according to comparison interventions- pharmacological and nonpharmacological; administered individually and/or in combination treatment of DPN population. Results: Of the final list of 56 included studies,there were five studies comparing placebo with non-pharmacological interventions which were on electrotherapy modalities in physical therapy namely static magnetic field therapy (n=1), Anodyne light therapymonochromatic infrared photoenergy (n=3), microcurrent electrical stimulation (n=1). 51 studies had compared placebo with pharmacological interventions that used combination therapy (n=3) and individual drugs administered either orally (n= 42), intravenously (n= 1), transdermally (n= 2) or topically (n= 3). Conclusion: There was prevalence of treatment-responders in Placebo groups in clinical trials of DPN on drug monotherapy whereas placebo was not effective against combination drug therapy. The study findings suggest an important role of placebo in research and practice of DPN. Evidence for placebo responses for non-pharmacological interventions such as exercise therapy and/or manual therapy was not found. 

Keywords: Placebo and nocebo; Psychosocial factors; Psychiatric neurorehabilitation; Clinical trials.