Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells.
OBJECTIVE
Xenon provides effective analgesia in several pain states at sub-anaesthetic doses. Our aim was to examine whether xenon may mediate its analgesic effect, in part, through reducing the activity of transient receptor potential vanilloid type 1 (TRPV1), a receptor known to be involved in certain inflammatory pain conditions.


METHODS
We studied the effect of xenon on capsaicin-evoked cobalt uptake in rat cultured primary sensory neurons and in human TRPV1 (hTRPV1)-expressing human embryonic kidney 293 (HEK293) cells. We also examined xenon's effect on the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the rat spinal dorsal horn evoked by hind-paw injection of capsaicin.


RESULTS
Xenon (75%) reduced the number of primary sensory neurons responding to the TRPV1 agonist, capsaicin (100 nM-1 μM) by ~25% to ~50%. Xenon reduced the number of heterologously-expressed hTRPV1 activated by 300 nM capsaicin by ~50%. Xenon (80%) reduced by ~40% the number of phosphorylated ERK1/2-expressing neurons in rat spinal dorsal horn resulting from hind-paw capsaicin injection.


CONCLUSIONS
Xenon substantially reduces the activity of TRPV1 in response to noxious stimulation by the specific TRPV1 agonist, capsaicin, suggesting a possible role for xenon as an adjunct analgesic where hTRPV1 is an active contributor to the excitation of primary afferents which initiates the pain sensation.
Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369, Fulham Road, London, SW10 9NH, United Kingdom.
John P M
JP
White
Guy
G
Calcott
Agnes
A
Jenes
Mahmuda
M
Hossein
Cleoper C
CC
Paule
Peter
P
Santha
John B
JB
Davis
Daqing
D
Ma
Andrew S C
AS
Rice
Istvan
I
Nagy
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin; D002460:Cell Line; D003035:Cobalt; D004594:Electrophysiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D050916:TRPV Cation Channels; D003035:Cobalt; D014978:Xenon; D048049:Extracellular Signal-Regulated MAP Kinases; D002211:Capsaicin