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Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test

Myrna Déciga-Campos, Pamela Moncerrat Ramírez-Marín, Francisco Javier López-Muñoz. Eur J Pharmacol. 2015;765:68-74.

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
Mice given an intraplantar formalin injection to produce pain
Dose used in the study
PEA (0.1-56.2 micrograms per paw) and tramadol (1-56.2 micrograms per paw), injected into the paw, alone and in a fixed 1:1 combination
Duration
Not stated in the abstract
What was measured
Pain response in the formalin test, using isobolographic analysis to test for synergy, and involvement of opioid receptors, TRPV1 channels and PPAR-alpha; sedation was also assessed

What the authors reported

PEA and tramadol combined produced a synergistic reduction in pain response: the effective combined dose (9.5 micrograms per paw) was lower than the dose calculated by adding the two drugs' individual effects (24.8 micrograms per paw). The combination's antinociceptive effect involved opioid receptors, TRPV1 and PPAR-alpha, and caused less sedation than either drug alone.

Limits of this study

A mouse model of formalin-induced pain; it cannot show effect in people. Funding and conflicts not stated in the abstract.

Source

PubMed 26297302 · doi:10.1016/j.ejphar.2015.08.025

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.