Effects of SR140333, a selective non-peptide NK1 receptor antagonist, on trigemino-thalamic nociceptive pathways in the rat.
Trigeminal stimulation of C-fibers increased c-fos expression within the trigeminal nucleus caudalis (NtV) and thalamic neuronal activity which both reflect the transmission of a nociceptive message. We examined the effects on both these phenomena of the selective NK1 and NK2 receptor antagonists, SR140333 and SR48968. SR140333 (0.3, 1 and 3 micrograms/kg intravenously [i.v.]) dose-dependently, reversibly and stereoselectively antagonized the increase of contralateral thalamic activity. This compound, when given i.v. (30 micrograms/kg) or orally (10 mg/kg), also reduced the number of Fos-like immunoreactive cells particularly at the medial and caudal level of the NtV. In contrast, SR48968 did not exert any antagonistic effect either on thalamic activity or on Fos-like immunoreactivity. The data strongly suggest a preferential involvement of NK1 vs NK2 receptors in nociceptive transmission following trigeminal ganglion stimulation. Taken together, our results indicate that SR140333 could provide a potent drug for the relief of pain occurring under excessive activity of sensory trigeminal fibers.
Michaud
J C
JC
Sanofi Recherche, Montpellier, France.
Alonso
R
R
Gueudet
C
C
Fournier
M
M
Calassi
R
R
Brelière
J C
JC
Le Fur
G
G
Soubrié
P
P
D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004558:Electric Stimulation; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008297:Male; D009434:Neural Pathways / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000503:physiopathology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013788:Thalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014278:Trigeminal Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; C085215:SR 140333; C073839:SR 48968