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Propofol-induced pain sensation involves multiple mechanisms in sensory neurons

  • Sensory physiology
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Abstract

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 Ca2+ 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 Ca2+ 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.

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Acknowledgments

We would like to thank Dr. Junichi Nabekura (Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki, Japan), Dr. Motohiro Nishida (Division of Cardiocirculatory Signaling, National Institute for Physiological Sciences, Okazaki, Japan), Dr. Hidemasa Furue (Division of Neural Signaling, National Institute for Physiological Sciences, Okazaki, Japan), and Dr. Hitoshi Ishibashi (School of Allied Health Sciences, Kitasato University, Kanagawa, Japan) for their helpful suggestion and discussion. This work was supported by grants to Makoto Tominaga from the Ministry of Education, Culture, Sports, Science and Technology in Japan.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Physiological Sciences, the Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi, 444-8585, Japan

    Rei Nishimoto & Makoto Tominaga

  2. Division of Cell Signaling, Okazaki Institute for Integrative Biosciences (National Institute for Physiological Sciences), Higashiyama 5-1, Myodaiji, Okazaki, Aichi, 444-8787, Japan

    Rei Nishimoto, Makiko Kashio & Makoto Tominaga

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  1. Rei Nishimoto
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Nishimoto, R., Kashio, M. & Tominaga, M. Propofol-induced pain sensation involves multiple mechanisms in sensory neurons. Pflugers Arch - Eur J Physiol 467, 2011–2020 (2015). https://doi.org/10.1007/s00424-014-1620-1

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