PubMed 25301522

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1 , TRPV , TRPV1

Title: Propofol-induced pain sensation involves multiple mechanisms in sensory neurons.

Authors: Rei Nishimoto, Makiko Kashio, Makoto Tominaga

Journal, date & volume: Pflugers Arch., 2015 Sep , 467, 2011-20

PubMed link:

Propofol, a commonly used intravenous anesthetic agent, is known to at times cause pain sensation upon injection in humans. However, the molecular mechanisms underlying this effect are not fully understood. Although propofol was reported to activate human transient receptor potential ankyrin 1 (TRPA1) in this regard, its action on human TRP vanilloid 1 (TRPV1), another nociceptive receptor, is unknown. Furthermore, whether propofol activates TRPV1 in rodents is controversial. Here, we show that propofol activates human and mouse TRPA1. In contrast, we did not observe propofol-evoked human TRPV1 activation, while the ability of propofol to activate mouse TRPV1 was very small. We also found that propofol caused increases in intracellular Ca(2+) concentrations in a considerable portion of dorsal root ganglion (DRG) cells from mice lacking both TRPV1 and TRPA1, indicating the existence of TRPV1- and TRPA1-independent mechanisms for propofol action. In addition, propofol produced action potential generation in a type A γ-amino butyric acid (GABAA) receptor-dependent manner. Finally, we found that both T-type and L-type Ca(2+) channels are activated downstream of GABAA receptor activation by propofol. Thus, we conclude that propofol may cause pain sensation through multiple mechanisms involving not only TRPV1 and TRPA1 but also voltage-gated channels downstream of GABAA receptor activation.