Search

Background: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported. Methods: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured. Results: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats. Conclusions: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.

Spinal serotonin (5-HT) receptors 3 (5-HT3R) and 7 (5-HT7R) are differentially involved in facilitatory or inhibitory descending modulation, respectively. Electrophysiological studies of the spinal cord have demonstrated that 5-HT3R is involved in nociception induced by intraplantar injection of formalin, but not carrageenan. In addition, depletion of spinal serotonin has been shown to attenuate pain behaviour in the formalin test, but there have been no such reports regarding the carrageenan model. This study compared the role of 5-HT7R and the influence of descending serotonergic modulation between formalin- and carrageenan-induced inflammatory pain.Effects of intrathecal (i.t.) AS-19 (5-HT7R agonist) and SB-269970 (5-HT3R antagonist) on flinching response in the formalin test and mechanical allodynia in the carrageenan model were evaluated in male Sprague-Dawley rats. The effect of serotonin depletion by i.t. 5,7-dihydroxytryptamine was also examined in the two models.Intrathecal AS-19 significantly reduced the flinching responses in the formalin test (P0.01), which was reversed by i.t. SB269970. However, neither AS-19 nor SB269970 produced a significant change in mechanical allodynia in the carrageenan model. Depletion of spinal serotonin attenuated the flinching response in phase 2 of the formalin test (P0.01), but increased mechanical allodynia in the carrageenan model compared with controls (P0.01).Spinal 5-HT7R plays a significant inhibitory role in descending serotonergic modulation in pain induced by formalin but not carrageenan. Descending serotonergic modulation is differentially involved in inflammatory pain induced by formalin and carrageenan, with facilitatory and inhibitory effects, respectively.

Background: This study was undertaken to compare the hemodynamic effects between desflurane inhalation and endotracheal intubation, and to evaluate the intensity of airway irritation by desflurane inhalation of high concentration. Methods: Twenty adult patients with ASA 1 were enrolled in this study. Radial artery was catheterized and heart rate (HR) and mean arterial pressure (MAP) were measured throughout the study. Anesthesia was induced by propofol and effect site concentration of propofol was maintained at 4/ml using target controlled infusor (TCI). Peak HR and MAP following tracheal intubation were recorded and inhalation of 12 vol% desflurane was started after HR and MAP had been returned to pre-intubation value. The HR, MAP, inspiratory (Fi) and end-tidal fraction (Et) were observed after desflurane inhalation for 10 minutes. Results: The HR and MAP were significantly increased after tracheal intubation and desflurane inhalation, and the peak hemodynamic change after desflurane inhalation was significantly delayed as compared to tracheal intubation. The maximal HR change from baseline after tracheal intubation or desflurane inhalation was not different, but maximal MAP change was significantly lower during desflurane inhalation compared with tracheal intubation. The maximal change of HR and MAP when end-tidal fraction of desflurane had been reached 6 vol% was lower than that of tracheal intubation or desflurane inhalation. Conclusions: Despite of propofol administration required for general anesthesia, the HR and MAP were significantly increased during desflurane inhalation of high concentration. In particular, the extent of HR increase during desflurane inhalation was similar to that by tracheal intubation.