Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells
2011
White, John P.M. | Calcott, Guy | Jenes, Agnes | Hossein, Mahmuda | Paule, Cleoper C. | Sántha, Péter | Davis, John B. | Ma, Daqing | Rice, Andrew S.C. | Nagy, István
AIMS: 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. MAIN 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. KEY FINDINGS: Xenon (75%) reduced the number of primary sensory neurons responding to the TRPV1 agonist, capsaicin (100nM–1μM) by ~25% to ~50%. Xenon reduced the number of heterologously-expressed hTRPV1 activated by 300nM capsaicin by ~50%. Xenon (80%) reduced by ~40% the number of phosporylated ERK1/2-expressing neurons in rat spinal dorsal horn resulting from hind-paw capsaicin injection. SIGNIFICANCE: 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.
显示更多 [+] 显示较少 [-]