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N-Palmitoylethanolamide enhances antinociceptive effect of tramadol in neuropathic rats

A Alejo-Martínez, G Bravo, F J López-Muñoz. Biomed Pharmacother. 2025 Jan:182:117760.

Laboratory studyOther animalsWith tramadol

This study tested palmitoylethanolamide together with tramadol. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
126 male Wistar rats with chronic constriction injury neuropathic pain, in 21 groups
Dose used in the study
Oral tramadol (1.0 to 31.62 mg/kg), PEA (0.0316 to 10 mg/kg), or combinations (tramadol 1.0 to 10 mg/kg with PEA 0.0316 to 1.0 mg/kg); gabapentin (1.0 to 177.78 mg/kg) as a comparator
Duration
Not stated in the abstract
What was measured
Anti-hyperalgesic and anti-allodynic effects by dose-response analysis; motor coordination; constipation; surface of synergistic interaction analysis.

What the authors reported

PEA alone was about five times more potent than tramadol against hyperalgesia and about eight times more potent against allodynia. The combination of tramadol 10 mg/kg plus PEA 0.0316 mg/kg gave the strongest anti-hyperalgesic and anti-allodynic effects among combinations tested, with no added effect on motor coordination or constipation compared with vehicle.

Limits of this study

A rat model of chronic constriction injury pain; it cannot show effect in people. The authors declare no competing financial interests.

Source

PubMed 39721328 · doi:10.1016/j.biopha.2024.117760

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.