Figure 2 Effects of oral pregabalin on the visceromotor responses to phasic ascending colorectal distension (CDR; 10�C80mmHg over 20min) in rats. Responses to CRD were determined simultaneously in the same animals by Tubacin solubility electromyographical … Thresholds for response to CRD in the vehicle-treated group were similar when assessing EMG activity or intraballoon pressure changes (Figures 2e and f). Pregabalin increased the threshold for responses of EMG (P=0.002 vs vehicle) or intraballoon pressure changes (P=0.005 vs vehicle) (Figures 2e and f). Effects of pregabalin on repetitive noxious CRD-induced cardiovascular responses In vehicle-treated animals (n=6), noxious CRD (80mmHg �� 12 pulses) elicited a visceromotor response similar to that described above (Figures 3a and b), and characterized by an increase in the EMG activity and the balloon pressure fluctuations during the duration of the distension pulses.

In addition, CRD evoked significant rises in blood pressure and heart rate (Figures 3c and d). When recording the EMG activity, the visceromotor response was similar in magnitude over the complete CRD protocol. However, when assessing the changes in intracolonic balloon pressure, the responses increased in magnitude by 85��33% from the first to the last pulse (F(5, 11)=6.076; P<0.001; P<0.05 for distensions 8�C12 vs distension 1). Similarly, the change in blood pressure also increased throughout the distension protocol by 63��27% (F(5, 11)=4.819, P<0.001; P<0.05 for distensions 7�C12 vs distension 1). The heart rate also increased during the distension time compared with the baseline activity.

However, the heart rate increased over time in only four out of six animals tested, therefore the presence of sensitization was not as clear (Figure 3c). After each pulse, blood pressure and heart rate returned to their baseline control values, which were stable over the experiment (?1��2 and ?6��1% change over the complete CRD protocol, respectively). Figure 3 Effects of oral pregabalin on the visceromotor and autonomic cardiovascular responses to repetitive noxious colorectal distension (CRD; 80mmHg) in rats. Visceromotor responses to CRD were determined simultaneously in the same animals … Pregabalin (200��molkg?1, p.o., n=6) attenuated the overall visceromotor response to CRD by 16��8 and 47��6%, as determined by EMG or colonic manometry, respectively (Figures 3a and b, both P<0.

05 vs respective response in the vehicle-treated group). A similar effect of pregabalin was also observed for CRD-induced blood pressure and heart rate changes, which were attenuated, overall, by 28��12% (P=0.018 Brefeldin_A vs vehicle; Figure 3c) and 25��8% (P=0.026 vs. vehicle; Figure 3d), respectively. Pregabalin, per se, had no effects on basal blood pressure (mean basal blood pressure at the beginning of the CRD procedure: vehicle, 118.3��5.1mmHg; pregabalin, 113.4��8.8mmHg; P>0.