Propofol reduces human TRPA1 activity in a warm environment

Abstract

Propofol, an intravenous anesthetic, has a side effect of causing vascular pain at the injection site. However, no effective method to inhibit this vascular pain has been established. Propofol-induced vascular pain is caused by activation of transient receptor potential ankyrin1 (TRPA1), which is expressed in the sensory nerve endings distributed around blood vessels. TRPA1 exhibits temperature sensitivity, and the degree of its activation has been reported to change with temperature. However, whether the temperature of propofol influences human TRPA1 (hTRPA1) activation and regulates the extent of vascular pain has not been examined. We investigated hTRPA1 activity in HEK293T cells in response to cooled or heated propofol using the patch-clamp method. We found that hTRPA1 currents were smaller in a warm environment (>35 °C) with heated propofol. Our results suggest that propofol should be kept above 35 °C to minimize hTRPA1 activation. Moreover, heating propofol decreased hTRPA1-mediated currents but did not alter activation of human GABA_A receptors. This finding suggest that heated propofol can inhibit hTRPA1 activation and reduce vascular pain without losing its anesthetic function.