Abstract Neuropathic pain, a complex condition resulting from somatosensory system damage, poses a significant clinical challenge due to the limited efficacy and side effects of current treatments. This study investigated the analgesic potential of three monoamine oxidase (MAO) inhibitors—moclobemide (MAO-A), phenelzine (non-selective), and rasagiline (MAO-B)—in a sciatic nerve ligation-induced neuropathic pain rat model (chronic constriction injury model). We also examined their effects on the levels of inflammatory factors TNF-α and IL-1β in the dorsal root ganglion (DRG). A total of 88 rats were divided into 11 experimental groups: a Sham group, an untreated neuropathic pain group, and nine treatment groups administered different doses of moclobemide, phenelzine, or rasagiline. Pain responses were assessed using the hot plate and tail-flick tests, and DRG tissues were analyzed for TNF-α and IL-1β concentrations via ELISA. The results confirmed the successful establishment of the neuropathic pain model, characterized by decreased pain thresholds and elevated TNF-α and IL-1β levels in the DRG. Both moclobemide and phenelzine demonstrated significant, dose-dependent analgesic effects in both the hot plate and tail-flick tests. Notably, moclobemide and phenelzine significantly reduced TNF-α and IL-1β levels. In contrast, rasagiline showed no analgesic effect; instead, the highest dose induced a hyperalgesic response. In conclusion, both moclobemide and phenelzine effectively reduce neuropathic pain and mitigate associated inflammation. Their cytokine-reducing effects likely contribute to their analgesic properties. Rasagiline, however, was ineffective and may exacerbate pain. These findings suggest that moclobemide and phenelzine hold promise as therapeutic agents for neuropathic pain, warranting further investigation into their mechanisms of action.
Gedikli et al. (2026) studied this question.