Involvement of Spinal Substance P and Excitatory Amino Acids in Inflammatory Hyperalgesia in Rats
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概要
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To reveal possible involvement of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the production of inflammatory hyperalgesia, we examined the effects of intrathecal injections of antagonists at those receptors on the nociceptive threshold of inflammatory hyperalgesic rats in the paw-pressure test. Intrathecal injections of the NK-1 antagonist CP-96, 345 (0.3 – 3 nmol/rat), the NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 1 – 10 nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX, 1 – 10 nmol/rat) dose-dependently suppressed adjuvant- and carrageenin-induced hyperalgesia, without effect on the nociceptive threshold of non-inflamed paws. Furthermore, to estimate whether inflammatory hyperalgesia is accompanied with an alteration of the responsiveness to substance P and excitatory amino acids, we examined the effects of injections of complete Freund’s adjuvant (intradermal) and carrageenin (subcutaneous) on the aversive responses to intrathecal substance P and excitatory amino acid agonists. Both injections significantly potentiated the aversive behaviors elicited by intrathecal injections of excitatory amino acid agonists, NMDA (1 nmol/rat), α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 1 nmol/rat) and kainate (1 nmol/rat), but not those by substance P. The present results suggest that the enhancement of synaptic transmission mediated by substance P and excitatory amino acids in the spinal dorsal horn is at least partly involved in the production of inflammatory hyperalgesia, and that such a hyperalgesia is accompanied with the enhanced responsiveness to excitatory amino acids through NMDA and non-NMDA receptors, but not with changes in responsiveness to substance P.
- 社団法人 日本薬理学会の論文
著者
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KURAISHI Yasushi
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, Univers
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Kuraishi Yasushi
富山大学 医学薬学研究部応用薬理学
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SATOH Masamichi
Department of molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto university
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OKANO Kazuhiko
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
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Okano Kazuhiko
Department Of Molecular Pharmacology Faculty Of Pharmaceutical Sciences Kyoto University
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Kuraishi Yasushi
Department Of Applied Pharmacology Faculty Of Pharmaceu Tical Sciences
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Satoh Masamichi
Department Of Molecular Pharmacology Faculty Of Pharmaceutical Science Kyoto University
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Kuraishi Yasushi
Department Of Applide Biochemistry Research Institute For Wakan-yaku Toyama Toyama Medical And Pharm
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Satoh Masamichi
Department Of Hygiene And Preventive Medicine Faculty Of Medicine Saitama Medical School
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