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Inhibition of cardiac baroreflex by noxious thermal stimuli: A key role for lateral paragigantocellular serotonergic cells

Gau, Rémia,b,c; Sévoz-Couche, Carolinea; Laguzzi, Raùla; Hamon, Michela,b,c; Bernard, Jean-Françoisa,b,c,*

doi: 10.1016/j.pain.2009.09.018
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ABSTRACT 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.

E-mail address:jean-francois.bernard@upmc.fr

ARTICLE INFO

Article history:

Received March 30, 2009

Received in revised form August 21, 2009

Accepted September 17, 2009.

© 2009 Lippincott Williams & Wilkins, Inc.
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