The Efficacy of Intradermal Injection of Botulinum Toxin Type-A on Painful Diabetic Neuropathy: A Systematic Review

Context: Diabetes is one of the most common causes of neuropathy. Morbidity and mortality increase in patients suffering from diabetic polyneuropathy and are experienced by approximately 10 to 54% of diabetic patients. Severe pain, loss of sensation, increased risk of ulceration, and even amputation are the complications of diabetic neuropathy. Intradermal injection of botulinum toxin type-A (BTX-A) is a relatively novel method for the treatment of painful diabetic neuropathy. This method is becoming popular considering its acceptable and long-lasting pain control and minimal systemic side effects.

Methods: This narrative systematic review aimed to evaluate the effectiveness of intradermal BTX-A injection on painful diabetic neuropathy. The queried databases included PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Web of Science, Scopus, and Google Scholar. The final search was performed in February 2022, and no time limits were set for the search. All the relevant clinical trials were included. The inclusion criteria and search strategy were set as follows: Type of study: Randomized clinical trial (RCT) or other types of interventional studies; publication date: All published studies until February 22, 2022; sample size: No restrictions; outcomes: Effect on diabetic neuropathy pain; quality: Earning a minimum acceptable score based on critical appraisal; and language: English. The searches and article screening were performed by two independent reviewers to minimize the possibility of bias. In case of disagreement about a study, the comments of an expert (as a third person) were used to resolve the ambiguity.

Results: In a review of 4 RCTs and 1 case-control study on the effectiveness of BTX-A in reducing the pain of diabetic neuropathy, 273 patients were evaluated in total. The lowest and highest number of subjects was 18 and 141. The sex distribution included 43.22% men and 56.77% women, all of whom were 47.8 to 74.8 years old. Three studies were conducted in Iran, Taiwan, and Egypt. The results of this review showed significant improvement in pain reduction, e.g., based on the Visual Analog Scale (VAS) and Neuropathic Pain Scale (NPS). A few studies evaluated sleep and psychosocial complications, and their results indicated a statistically significant improvement in the Pittsburgh sleep quality index (PSQI) and the physical subscale of the 36-Item Short Form Survey (SF-36).

Conclusions: The results of this systematic review demonstrated that intradermal injection of BTX-A causes significant and long-term (up to 12 weeks) improvement in diabetic neuropathy pain. The improvement in sleep and mental or physical functions was not consistent, and no conclusive result could be reached.