# A Review of the Prospective Effects of Methadone on Peripheral Neuropathic Pain in Diabetic Patients

## TL;DR

This review examines how methadone affects neuropathic pain in diabetic patients, highlighting its potential benefits and mechanisms.

## Contribution

The paper provides a comprehensive review of methadone's effects on diabetic neuropathic pain and its immunomodulatory mechanisms.

## Key findings

- Low-dose methadone reduced visual analog scale (VAS) scores and serum glucose levels in diabetic patients.
- Methadone increased N-chlorotaurine production, which supports innate immunity.
- Methadone elevated levels of TNF-α, IL-1β, IL-2, and CD14+ monocytes in a dose-dependent manner.

## Abstract

Peripheral neuropathic pain (PNP) is a significant complication for diabetic patients, often linked to poor glycemic control and elevated levels of glycosylated hemoglobin (HbA1c). High serum levels of cytokines, such as interleukin (IL)-6, and an increase in T-lymphocytes are crucial factors in developing neuropathic complications. Research suggests that substances like opiates and methadone can provide pain relief for these patients. This literature review is aimed at exploring the advantages and disadvantages of prescribing methadone to individuals with diabetes. We conducted a search of several databases, including PubMed, Google Scholar, Medline, Embase, Web of Science, and Scopus. We used keywords such as “diabetes,” “neuropathic pain,” “methadone,” “opioids,” “inflammation,” and “neuroimmunomodulation.” Ultimately, we identified 19 articles suitable for a more detailed examination. Studies have revealed that the visual analog scale (VAS) index and serum glucose levels decreased in patients who had taken low-dose methadone. Additionally, the production of N-chlorotaurine, a crucial component for innate immunity, was increased in these individuals. Methadone, in a dose-dependent manner, is accountable for increasing serum levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-2 (IL-2) and a high number of monocyte CD14+. In conclusion, there were several advantages to taking methadone in a dose-dependent manner, compared to opioids.