PMID- 25301522
OWN - NLM
STAT- MEDLINE
DCOM- 20160518
LR  - 20211021
IS  - 1432-2013 (Electronic)
IS  - 0031-6768 (Linking)
VI  - 467
IP  - 9
DP  - 2015 Sep
TI  - Propofol-induced pain sensation involves multiple mechanisms in sensory neurons.
PG  - 2011-20
LID - 10.1007/s00424-014-1620-1 [doi]
AB  - 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 gamma-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.
FAU - Nishimoto, Rei
AU  - Nishimoto R
AD  - Department of Physiological Sciences, the Graduate University for Advanced 
      Studies (SOKENDAI), Okazaki, Aichi, 444-8585, Japan.
FAU - Kashio, Makiko
AU  - Kashio M
FAU - Tominaga, Makoto
AU  - Tominaga M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141010
PL  - Germany
TA  - Pflugers Arch
JT  - Pflugers Archiv : European journal of physiology
JID - 0154720
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Calcium Channels)
RN  - 0 (Receptors, GABA-A)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Anesthetics, Intravenous/*adverse effects
MH  - Animals
MH  - Calcium Channels/*drug effects/metabolism
MH  - Ganglia, Spinal/drug effects/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pain/*chemically induced/metabolism
MH  - Patch-Clamp Techniques
MH  - Propofol/*adverse effects
MH  - Receptors, GABA-A/drug effects/metabolism
MH  - Sensory Receptor Cells/*drug effects/metabolism
EDAT- 2014/10/11 06:00
MHDA- 2016/05/19 06:00
CRDT- 2014/10/11 06:00
PHST- 2014/06/18 00:00 [received]
PHST- 2014/09/25 00:00 [accepted]
PHST- 2014/09/22 00:00 [revised]
PHST- 2014/10/11 06:00 [entrez]
PHST- 2014/10/11 06:00 [pubmed]
PHST- 2016/05/19 06:00 [medline]
AID - 10.1007/s00424-014-1620-1 [doi]
PST - ppublish
SO  - Pflugers Arch. 2015 Sep;467(9):2011-20. doi: 10.1007/s00424-014-1620-1. Epub 2014 
      Oct 10.