Inhibition of cardiac baroreflex by noxious thermal stimuli: a key role for lateral paragigantocellular serotonergic cells.
The present study was designed to identify the neuronal mechanisms causing cardiac baroreflex inhibition associated with thermal nociception in rats. Under urethane-anesthesia, noxious thermal stimuli > or = 48 degrees C were found to inhibit the cardiac baroreflex, whereas noxious stimuli < or = 46 degrees C had no effect. Using double immunohistochemical labeling, noxious stimuli > or = 48 degrees C were found to evoke primarily a strong expression of Fos protein (Fos) encoded by c-fos gene in serotonergic neurons of lateral paragigantocellular reticular nucleus (LPGi). Noxious stimuli < or = 46 degrees C did not evoke Fos expression in any serotonergic neurons of the brainstem. Local blockade of neuronal activity by bilateral microinjections of fluorescent muscimol (a GABA(A) receptor agonist tagged with a fluorophore that allowed visualization of the injections) into both the LPGi and the raphe magnus nucleus prevented the inhibitory effect of noxious stimuli > or = 48 degrees C on the cardiac baroreflex. Bilateral microinjections of granisetron (a 5-HT(3) antagonist) within the nucleus tractus solitarius also prevented the inhibition of cardiac baroreflex elicited by noxious stimuli > or = 48 degrees C. These results show that activation of serotonergic cells in the LPGi is critical to trigger nucleus tractus solitarius-mediated cardiac baroreflex inhibition elicited by intense thermal noxious stimuli.
Gau
Rémi
R
Université Pierre et Marie Curie - Paris 6, Site Pitié-Salpêtrière, UMR 894, Paris, France Université Paris Descartes - Paris 5, France Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France.
Sévoz-Couche
Caroline
C
Laguzzi
Raùl
R
Hamon
Michel
M
Bernard
Jean-François
JF
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D005456:Fluorescent Dyes; D018755:GABA Agonists / Q000494:pharmacology; D016762:Genes, fos; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006358:Hot Temperature; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017552:Solitary Nucleus / Q000503:physiopathology*
D005456:Fluorescent Dyes; D018755:GABA Agonists; D017829:Granisetron; D009118:Muscimol; D012701:Serotonin; D012702:Serotonin Antagonists