Low dose of kyotorphin (tyrosine-arginine) induces nociceptive responses through a substance P release from nociceptor endings.
The intraplantar injection of kyotorphin (Kyo) elicited nociceptive flexor responses in mice in a dose-dependent manner between 0.1 and 100 fmol. These actions were completely blocked by substance P (NK1) receptor antagonists, such as CP-96345 and CP-99994, but not by their inactive derivatives, CP-96344 or CP-100263, nor by MEN-10376, an NK2 antagonist. Kyo-responses were also abolished by the local pretreatment with capsaicin to deplete substance P from nociceptor endings, and in tachykinin 1 gene K/O mice. These findings suggest that Kyo indirectly stimulates nociceptor endings through a local substance P release.
Inoue
M
M
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Yamada
T
T
Ueda
H
H
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009411:Nerve Endings / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000503:physiopathology*; D013373:Substance P / Q000378:metabolism*
D004723:Endorphins; D064729:Neurokinin-1 Receptor Antagonists; C019448:kyotorphin; D013373:Substance P; D002211:Capsaicin