Involvement of glial cells in the nociceptive behaviors induced by a high-dose of histamine administered intrathecally.
The involvement of spinal glial cells in the nociceptive behaviors induced by 1600 pmol of histamine was determined in mice. Histamine 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. pretreatment with the glial cell inhibitor DL-fluorocitric acid or minocycline. In Western blot analysis using lumber spinal cords, i.t. treatment with histamine increased the phosphorylation of the NR1 subunit of N-methyl-D-aspartate (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. We have previously reported that the nociceptive behaviors induced by 1600 pmol of histamine were significantly suppressed by the i.t. co-administration of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine (MK-801), an ion channel blocker of NMDA receptors, or agmatine, an antagonist for the polyamine recognition site on the NR1 subunit of NMDA receptors. In the present study, the increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was also abolished by i.t. co-administration of agmatine or MK-801. The present results suggest that histamine at 1600 pmol elicits nociceptive behaviors by stimulating the polyamine recognition site on the NR1 subunit of NMDA receptors on spinal glial cells.
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Japan.
Hirokazu
H
Mizoguchi
Takaaki
T
Komatsu
Yoko
Y
Iwata
Chizuko
C
Watanabe
Hiroyuki
H
Watanabe
Tohru
T
Orito
Soh
S
Katsuyama
Akihiko
A
Yonezawa
Kenji
K
Onodera
Tsukasa
T
Sakurada
Shinobu
S
Sakurada
D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000376:Agmatine; D006632:Histamine