In an unique video fragment professor Montalcini explains all the above issues (at the age of around 90!)
Mast cell as important players in inflammation and pain
Levi-Montalcini also stressed the importance of mast cell activity in activated plaques in MS patients, and the pathological cascade of events triggered by these activated mast cells. In the same period (around 1990) she proved that mast cells can be sources of the synthesis of nerve growth factor, the base of the pathological immune system-CNS crosstalk.
In an authoritative review article on nerve growth factors, in TINS 1996, Montalcini already asked attention for the therapeutic potential of palmitoylethanolamide in neuropathic pain and multiple sclerosis.
In that famous article Levi Montalcini wrote about palmitoylethanolamide and the mast cell:
…unregulated mast-cell activation constitutes a considerable risk to the health of the organism, and it is not unreasonable to expect that nature should have devised a means for the host to defend itself against such damage.
It has recently been proposed that saturated N-acylethanolamides like palmitoylethanolamide, which accumulate in tissues following injury and which downmodulate mast-cell activation in vitro, exert a local, autacoid, anti-injury function via mast cells.
Palmitoylethanolamide is orally active in reducing tissue inflammation and mast-cell degranulation in vivo, in decreasing hyperalgesia that accompanies peripheral nerve compression, and in limiting the neurological deficits of experimental allergic encephalomyelitis.
Moreover, palmitoylethanolamide appears to project against excitotoxic neuronal death in vitro and to be produced by cultured CNS neurones upon excitatory amino acid receptor activation.
The mechanism of this action of N-acylethanolamides has been termed autacoid local injury antagonism (ALIA).
The observed pharmacological effects of palmitoylethanolamide appear to reflect the consequences of supplying the tissue with a sufficient quantity of its physiological regulator of cellular homeostasis.
And concluding, and how right she was:
Conceivably, palmitoylethanolamide and its congeners (‘ALIAmides’) might play a role in modulating cellular defence mechanisms by acting at non-CB1 cannabinoid receptors. The activation of such receptors might down-modulate deleterious cellular processes following pathological events or noxious stimuli in both the immune and nervous systems…..