title: Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.
abstract: The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord.
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iwata
authors.forename: Chizuko
authors.initials: C
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Tohru
authors.initials: T
authors.lastname: Orito
authors.forename: Soh
authors.initials: S
authors.lastname: Katsuyama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Onodera
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
mesh_terms: D000818:Animals; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology* / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D058748:Pain Perception / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: C409466:NR1 NMDA receptor; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D006632:Histamine