Antineuropathic Profile of N-Palmitoylethanolamine in a Rat Model of Oxaliplatin-Induced Neurotoxicity

摘要: Neurotoxicity is a main side effect of the anticancer drug oxaliplatin. The development neuropathic syndrome impairs quality life and potentially results in chemotherapy dose reductions and/or early discontinuation. In complex pattern molecular morphological alterations induced by oxaliplatin nervous system, an important activation glia has been preclinically evidenced. N-Palmitoylethanolamine (PEA) modulates glial cells exerts antinociceptive effects several animal models. order to improve therapeutic chances for chemotherapy-dependent neuropathy management, role PEA was investigated rat model oxaliplatin-induced (2.4 mg kg-1 daily, intraperitoneally). On day 21, single administration (30 i.p.) able reduce oxaliplatin-dependent pain mechanical thermal stimuli. repeated treatment with daily i.p. 21 days, from first injection) prevented lowering threshold as well increased on suprathreshold stimulation. Ex vivo histological analysis dorsal root ganglia, peripheral nerves spinal cord highlighted neuroprotective glia-activation prevention administration. protective resulted normalization electrophysiological activity nociceptive neurons. Finally, did not alter mortality human colon cancer cell line HT-29. efficacy control preventing tissue alteration candidates this endogenous compound disease modifying agent. These characteristics, joined safety profile, suggest usefulness chemotherapy-induced neuropathy.