New insights in the mechanisms of opioid analgesia and tolerance: Ultramicronized palmitoylethanolamide down-modulates vascular endothelial growth factor-A in the nervous system
Laboratory studyOther animalsWith morphine
This study tested palmitoylethanolamide together with morphine. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.
- Design
- Laboratory study
- Subjects
- Animal model of morphine tolerance
- Dose used in the study
- Not stated in the abstract
- Duration
- Not stated in the abstract
- What was measured
- Onset of morphine tolerance; morphine analgesic activity; VEGF-A levels in the nervous system; comparison with anti-VEGF-A antibody bevacizumab; soluble VEGF receptor 1 (sFLT-1) and pain-related gene expression (Serpina3n, Eaat2) in dorsal root ganglia and spinal cord.
What the authors reported
The study found:
- Ultramicronised PEA, given before and with morphine, delayed morphine tolerance and boosted morphine's analgesic effect while countering morphine-induced VEGF-A increases in the nervous system, similar to bevacizumab, which also had an analgesic effect on its own.
- PEA lowered VEGF-A in dorsal root ganglia and spinal cord and lowered soluble VEGF receptor 1 in plasma versus morphine alone at equal analgesic doses.
- PEA also counteracted a more than 3-fold morphine-induced rise in Serpina3n and Eaat2 gene expression.
Limits of this study
An animal study; it cannot show effect in people taking morphine for pain. Carla Ghelardini and Lorenzo Di Cesare Mannelli received a grant from Epitech (Padua, Italy), which makes ultramicronised PEA.
Source
PubMed 39448045 · doi:10.1016/j.phrs.2024.107472
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.