title: Intrathecally-administered histamine facilitates nociception through tachykinin NK1 and histamine H1 receptors: a study in histidine decarboxylase gene knockout mice.
abstract: Intrathecal injection of histamine elicited behavioral responses consisting of scratching, biting and licking in conscious mice. To study the participation of histamine in pain perception, histidine decarboxylase knockout mice were examined for pain threshold by means of three different kinds of noxious stimuli: thermal nociception (hot-plate, tail-flick, and paw-withdrawal), mechanical nociception (tail-pressure), and chemical nociception (formalin test and capsaicin test). Mutant mice lacking histidine decarboxylase showed significantly fewer nociceptive responses to the hot-plate, tail-flick, paw-withdrawal, tail-pressure, formalin and capsaicin tests. Sensitivity to noxious stimuli in the histidine decarboxylase knockout mice was significantly lower when compared to the wild-type mice. The intrathecally-administered histamine (400 pmol) significantly shortened the latency in the histidine decarboxylase knockout mice, but not in the wild-type mice in tail-flick tests. Pyrilamine, a histamine H(1) receptor antagonist, but not ranitidine, a histamine H(2) receptor antagonist, produced inhibition of the induced behavioral responses in the tail-flick test when co-administered with histamine. Sendide, a tachykinin NK(1) receptor antagonist, inhibited histamine-induced nociceptive behavior in the histidine decarboxylase knockout mice. In contrast, the treatment with D-(-)-2 amino-5-phosponovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist, did not prevent the induction of the behavioral responses by histamine. These studies substantiate the evidence that nociceptive behavior induced by intrathecal injection of histamine is largely mediated through tachykinin NK(1) and histamine H(1) receptors in the spinal cord.
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Jalal Izadi
authors.initials: JI
authors.lastname: Mobarakeh
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakurai
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Tohru
authors.initials: T
authors.lastname: Orito
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde; D006632:Histamine / Q000008:administration & dosage*; D006640:Histidine Decarboxylase / Q000235:genetics; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D011969:Receptors, Histamine H1; D018040:Receptors, Neurokinin-1; D005557:Formaldehyde; D013373:Substance P; C032292:substance P (6-11); D015763:2-Amino-5-phosphonovalerate; D006632:Histamine; D006640:Histidine Decarboxylase; D002211:Capsaicin; D011761:Pyrrolidonecarboxylic Acid