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Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats.
Jpn J Pharmacol. 1998 Jan; 76(1):15-22.JJ

Abstract

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), a-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.

Authors+Show Affiliations

Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9517400

Citation

Okano, K, et al. "Involvement of Spinal Substance P and Excitatory Amino Acids in Inflammatory Hyperalgesia in Rats." Japanese Journal of Pharmacology, vol. 76, no. 1, 1998, pp. 15-22.
Okano K, Kuraishi Y, Satoh M. Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats. Jpn J Pharmacol. 1998;76(1):15-22.
Okano, K., Kuraishi, Y., & Satoh, M. (1998). Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats. Japanese Journal of Pharmacology, 76(1), 15-22.
Okano K, Kuraishi Y, Satoh M. Involvement of Spinal Substance P and Excitatory Amino Acids in Inflammatory Hyperalgesia in Rats. Jpn J Pharmacol. 1998;76(1):15-22. PubMed PMID: 9517400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats. AU - Okano,K, AU - Kuraishi,Y, AU - Satoh,M, PY - 1998/3/28/pubmed PY - 1998/3/28/medline PY - 1998/3/28/entrez SP - 15 EP - 22 JF - Japanese journal of pharmacology JO - Jpn J Pharmacol VL - 76 IS - 1 N2 - 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), a-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. SN - 0021-5198 UR - https://www.unboundmedicine.com/medline/citation/9517400/Involvement_of_spinal_substance_P_and_excitatory_amino_acids_in_inflammatory_hyperalgesia_in_rats_ L2 - https://joi.jlc.jst.go.jp/JST.JSTAGE/jjp/76.15?from=PubMed DB - PRIME DP - Unbound Medicine ER -