Involvement of transient receptor potential vanilloid subfamily 1 in endothelin-1-induced pain-like behavior.
Although local administration of endothelin-1 (ET-1) is known to evoke spontaneous pain, the mechanism of ET-1-induced pain has not been elucidated. We investigated the involvement of protein kinase C (PKC) and transient receptor potential vanilloid subfamily 1 (TRPV1) in ET-1-induced pain-like behavior. Intraplantar ET-1 evoked pain-like behaviors, including licking, flinching, and biting, in a dose-dependent manner in wild-type mice. ET-1-induced pain-like behavior was attenuated by an endothelin type A receptor antagonist but not by PKC inhibitors and was also attenuated in TRPV1-deficient (KO) mice. In addition, we found a significant reduction of spinal Fos expression caused by the same dose of ET-1 in KO mice compared with that in wild-type mice. This study showed that endothelin type A receptor and TRPV1 are involved in ET-1-induced pain-like behaviors but failed to reveal the contribution of PKC.
Kawamata
Tomoyuki
T
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. kawamata@sapmed.ac.jp
Ji
Wenjin
W
Yamamoto
Jun
J
Niiyama
Yukitoshi
Y
Furuse
Shingo
S
Omote
Keiichi
K
Namiki
Akiyoshi
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics*
D015415:Biomarkers; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D044022:Receptor, Endothelin A; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D011493:Protein Kinase C