In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30 mg kg(-1) PEA was subcutaneously daily administered in morphine treated rats (10 mg kg(-1) intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-α levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-α immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested.
Italian and Dutch PEA
Palmitoylethanolamide is especially in Italy and the USA at the moment hot for the treatment of glaucoma. We prefer treatment either with the Italian PEA tablets, based on PEA-um or PEA-m, or by administrating the Dutch PEA capsules containing PEA-opt. Dutch capsules do not contain any chemical excipients and are 100% pure in vegetarian capsules.
Only for these the Dutch and the Italian formulations long term safety and efficacy data gathered under the supervision of MDs are available. And only for these formulations (PEA-um, PEA-m and PEA-opt) there are currently data available proving that after intake PEA levels in the body significantly rise. Such data do not exist for me-too PEA formulations.
Delay of morphine tolerance by palmitoylethanolamide.
Di Cesare Mannelli L, Corti F, Micheli L, Zanardelli M, Ghelardini C.
Biomed Res Int. 2015;2015:894732. doi: 10.1155/2015/894732. Epub 2015 Mar 22.1.