Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells

John P M White, Guy Calcott, Agnes Jenes, Mahmuda Hossein, Cleoper C. Paule, P. Sántha, John B. Davis, Daqing Ma, Andrew S C Rice, I. Nagy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 (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 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.

Original languageEnglish
Pages (from-to)141-149
Number of pages9
JournalLife Sciences
Volume88
Issue number3-4
DOIs
Publication statusPublished - 2011

Fingerprint

Xenon
Spinal Ganglia
Rats
Capsaicin
Chemical activation
Kidney
Neurons
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Sensory Receptor Cells
Pain
Analgesics
vanilloid receptor subtype 1
Phosphorylation
Injections
Cobalt
Analgesia
Anesthetics

Keywords

  • Analgesia
  • Post-operative pain
  • TRPV1
  • Xenon

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells. / White, John P M; Calcott, Guy; Jenes, Agnes; Hossein, Mahmuda; Paule, Cleoper C.; Sántha, P.; Davis, John B.; Ma, Daqing; Rice, Andrew S C; Nagy, I.

In: Life Sciences, Vol. 88, No. 3-4, 2011, p. 141-149.

Research output: Contribution to journalArticle

White, John P M ; Calcott, Guy ; Jenes, Agnes ; Hossein, Mahmuda ; Paule, Cleoper C. ; Sántha, P. ; Davis, John B. ; Ma, Daqing ; Rice, Andrew S C ; Nagy, I. / Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells. In: Life Sciences. 2011 ; Vol. 88, No. 3-4. pp. 141-149.
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