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N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice

Myrna Déciga-Campos, Osmar Antonio Jaramillo-Morales, Josué Vidal Espinosa-Juárez, María Elena Aguilera-Martínez, Rosa Ventura-Martínez, Francisco Javier López-Muñoz. J Pharm Pharmacol. 2023 Sep 1;75(9):1154-1162.

Laboratory studyOther animalsWith morphine and gabapentin (each tested separately in combination with palmitoylethanolamide)

This study tested palmitoylethanolamide together with morphine and gabapentin (each tested separately in combination with palmitoylethanolamide). Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
Female mice with intraplantar formalin-induced nociception
Dose used in the study
Palmitoylethanolamide, morphine and gabapentin given alone or combined by intraplantar injection; isobolographic analysis at a 1:1 ratio
Duration
Not stated in the abstract
What was measured
Antinociception in the formalin test, comparing individual dose-response curves with combinations, and the role of PPAR-alpha and opioid receptors using the antagonists GW6471 and naloxone

What the authors reported

This laboratory study found:

  • Potency order was morphine greater than palmitoylethanolamide greater than gabapentin.
  • Combining palmitoylethanolamide with morphine or gabapentin produced antinociception at doses below those predicted by simple addition (experimental flinching values of 2.72 and 2.77 micrograms/paw versus predicted 7.78 and 24.05 micrograms/paw), indicating synergy.
  • GW6471 and naloxone blocked the effect, implicating PPAR-alpha and opioid receptors.

Limits of this study

A mouse model using intraplantar formalin injection; it cannot show effect in people. Funding and conflicts not stated in the abstract.

Source

PubMed 36905375 · doi:10.1093/jpp/rgad004

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.