Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide that has garnered scientific attention for its potential analgesic and anti-inflammatory properties. Several clinical studies and systematic reviews have investigated its efficacy in neuropathic pain conditions, including sciatica. Evidence suggests that PEA may help reduce pain intensity and improve functional outcomes in patients with sciatic nerve compression or irritation.

The mechanism of action is thought to involve the modulation of mast cell activity and downregulation of pro-inflammatory mediators, as well as indirect effects on cannabinoid receptors. Notably, a 2010 double-blind, placebo-controlled trial (Gatti et al.) involving patients with sciatic pain found that PEA supplementation significantly reduced pain compared to placebo. Subsequent meta-analyses and reviews have supported these findings, though many emphasize the need for larger, high-quality randomized controlled trials to further establish efficacy and optimal dosing.

Overall, the current body of evidence supports a moderate scientific basis for the use of PEA in the management of sciatica, primarily as an adjunctive therapy. However, it should not be considered a first-line treatment, and clinicians are encouraged to consider individual patient factors and current guidelines when recommending PEA for sciatica.