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 ≥48 °C were found to inhibit the cardiac baroreflex, whereas noxious stimuli ≤46 °C had no effect. Using double immunohistochemical labeling, noxious stimuli ≥48 °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 ≤46 °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 GABAA 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 ≥48 °C on the cardiac baroreflex. Bilateral microinjections of granisetron (a 5-HT3 antagonist) within the nucleus tractus solitarius also prevented the inhibition of cardiac baroreflex elicited by noxious stimuli ≥48 °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.
aUniversité Pierre et Marie Curie – Paris 6, Site Pitié-Salpêtrière, UMR 894, Paris, France
bUniversité Paris Descartes – Paris 5, France
cCentre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France
*Corresponding author. Address: INSERM U894 (ex U677), 91 Boulevard de l’Hôpital, 75634 Paris Cedex 13, France. Tel.: +33 1 40 77 97 14; fax: +33 1 40 77 97 90.
Received March 30, 2009
Received in revised form August 21, 2009
Accepted September 17, 2009.