title: Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice.
abstract: The most recently identified tachykinin, hemokinin-1, was cloned from mouse bone marrow. While several studies indicated that hemokinin-1 is involved in pain and inflammation, the physiological functions of hemokinin-1 are not fully understood. Our previous research demonstrated that the intrathecal (i.t.) administration of hemokinin-1 (0.00625-1.6 nmol) dose-dependently induced nociceptive behaviors, consisting of scratching, biting and licking in mice, which are very similar with the nociceptive behaviors induced by the i.t. administration of substance P. Low-dose (0.0125 nmol) hemokinin-1-induced nociceptive behavior was inhibited by a specific NK1 receptor antagonist; however, high-dose (0.1 nmol) hemokinin-1-induced nociceptive behavior was not affected. In the present study, we found that the nociceptive behaviors induced by hemokinin-1 (0.1 nmol) were inhibited by the i.t. co-administration of MK-801 or D-APV, which are NMDA receptor antagonists. Moreover, we measured glutamate in the extracellular fluid of the mouse spinal cord using microdialysis. The i.t. administration of hemokinin-1 produced a significant increase in glutamate in the spinal cord, which was significantly reduced by co-administration with NMDA receptor antagonists. These results suggest that hemokinin-1-induced nociceptive behaviors may be mediated by the NMDA receptor 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: Chizuko
authors.initials: C
authors.lastname: Watanabe
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.affiliation: Department of Pharmacobiology, University of Calabria, Arcavacata di Rende, Cosenza 87036, Italy.
authors.forename: Giacinto
authors.initials: G
authors.lastname: Bagetta
authors.affiliation: Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address: s-sakura@tohoku-pharm.ac.jp.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D059225:Nociception; D010146:Pain / Q000503:physiopathology / Q000523:psychology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000378:metabolism*; D015320:Tachykinins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D015320:Tachykinins; C507968:hemokinin-1; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate
keywords: Glutamate; Hemokinin-1; Microdialysis; NMDA receptor; Pain; Spinal cord