Effects of intrathecally injected glutamate and substance P antagonists on repeated cold stress-induced hyperalgesia in rats.
To determine the role of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal horn in the hyperalgesia induced by repeated cold stress (RCS), we examined the effects of intrathecal injections of antagonists to NK-1, NMDA and non-NMDA receptors on the nociceptive threshold of RCS rats for paw-pressure stimulation. Intrathecal injections of the NK-1 antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (CP-96,345, 0.3-3 nmol/rat), the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV, 1-10nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) suppressed RCS-induced hyperalgesia in a dose-dependent manner, without affecting the nociceptive threshold of normal rats. Combinations of any two of CP-96,345 (3 nmol/rat), APV (10 nmol/rat), and CNQX (10 nmol/rat) did not produce a larger inhibition than that produced by their single doses. The present results suggest that the enhancement of the substance P-NK-1 receptor system and glutamate-NMDA and non-NMDA receptor systems in the spinal dorsal horn is at least partly involved in the RCS-induced hyperalgesia.
Okano
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Kuraishi
Y
Y
Satoh
M
M
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000150:complications*; D013373:Substance P / Q000037:antagonists & inhibitors*
D001713:Biphenyl Compounds; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D064729:Neurokinin-1 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C066892:CP 96345