Regeneration of mechanical sciatic nerve injury is affected by cold and heat exposure: involvements of the TRPM2 and TRPM8 channels

Background: Mechanical sciatic nerve (MSN) injury has a high rate within trauma cases. Heat and cold exposure in the treatments of MSN injuries have been clinically used in human. The MSN injury results in apoptosis, overload Ca2+ influx, and reactive oxygen species (ROS) generation in the sciatic nerve. TRPM2 and TRPM8 cation channels are activated by ROS. TRPM2 is activated by warmth (36-38 degrees C) and heat (45-47 degrees C), although TRPM8 is activated by cold (0-25 degrees C). Heat or cold exposure may aid recovery MSN injury through modulation of TRPM2 and TRPM8 in sciatic nerve. Objective: The protective roles of cold and heat treatments via modulation of TRPM2 and TRPM8 were evaluated on MSN injury-induced neurotoxicity in in vitro models of mouse and the SH-SY5Y cell line. Method: The mice sciatic nerves and SH-SY5Y cells were divided into control (37 degrees C), cold (10 degrees C), and moderate heat (40 degrees C) groups. Results: Our data identified a decrease in injury diameter in the neurons following heat exposure, but not cold exposure. In addition, the results of laser confocal microscopy analyses were indicative of a protective role of TRPM8 antagonist (ACA) against cold-induced increases in Ca2+ influx in the sciatic nerve and TRPM8 expressing SH-SY5Y cells. The results of the automatic plate reader and laser confocal microscope assays indicated a protective role of heat treatment against MSN injury-induced increases in apoptosis, mitochondrial ROS, cytosolic ROS, caspase -3, and -9 in the neurons. Conclusions: The heat treatment via possible modulation of TRPM2 channel and heat shock proteins induced protective actions against injury-mediated increases of oxidative stress, excitotoxicity, and apoptosis in the sciatic nerve and SH-SY5Y cells.