Possible involvement of tachykinin NK(1) and NMDA receptors in histamine-induced hyperalgesia in mice.
Intrathecal (i.t.) injection of histamine elicited a significant hyperalgesic response as assayed by the tail-flick test. This hyperalgesic effect peaked at 15 min following i.t. administration of histamine (800 pmol) and returned to control level with 30 min. Hyperalgesia produced by histamine was inhibited dose-dependently by i.t. co-administration of the histamine H(1) receptor antagonist, d-chlorpheniramine, but not the histamine H(2) receptor antagonist, ranitidine. The tachykinin NK(1) receptor antagonists, (+)-[(2S,3S)-3-(2-methoxy-benzyl-amino)-2-phenylpiperidine] (CP-99,994), and [Tyr(6), D-Phe(7), D-His(9)]substance P-(6-11) (sendide), inhibited histamine-induced hyperalgesic response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]substance P-(6-11), a selective antagonist for substance P receptors, was observed against histamine-induced hyperalgesic response. The tachykinin NK(2) receptor antagonist, Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH(2) (MEN-10,376), had no effect on hyperalgesia elicited by histamine. The competitive N-methyl-D-aspartate (NMDA) receptor antagonists, and D-(-)-2-amino-5-phosphonovaleric acid (D-APV), (+/-)-3-(2-carboxypiperazin-yl)propyl-1-phosphoric acid (CPP), the noncompetitive NMDA receptor antagonist dizocilpine (MK-801), and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, markedly inhibited histamine-induced hyperalgesic response. The present results suggest that hyperalgesic response induced by i.t. injection of histamine may be mediated by tachykinin NK(1) receptors, but not NK(2) receptors in the spinal cord. In addition, spinal NMDA receptor-NO system may also contribute to elicitation of hyperalgesia following i.t. injection of histamine.
Sakurada
Shinobu
S
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. s-sakura@tohoku-u.ac.jp
Orito
Tohru
T
Sakurada
Chikai
C
Sato
Takumi
T
Hayashi
Takafumi
T
Mobarakeh
Jalal Izadi
JI
Yanai
Kazuhiko
K
Onodera
Kenji
K
Watanabe
Takehiko
T
Sakurada
Tsukasa
T
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D006633:Histamine Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D006632:Histamine