1��molL?1). Statistical analysis Data are expressed as mean��s.e.mean. Differences between two groups were assessed by a paired or unpaired Student’s t-test, as appropriate. Differences between multiple groups were determined by a repeated or non-repeated measure one-way ANOVA, as appropriate, selleck chem KPT-330 followed, when necessary, by a Student�CNewman�CKeuls multiple comparisons test. Data were considered statistically significant when P<0.05. Drugs Pregabalin ((S)-(+)-3-(aminomethyl)-5-methylhexanoic acid) (AstraZeneca R&D) was dissolved in 0.9% saline solution at the appropriate concentration. Saline solution was used as vehicle control.
Results Effects of pregabalin on visceromotor responses to repetitive noxious CRD In vehicle-treated animals, noxious CRD (80mmHg) evoked a visceromotor response observed as simultaneous changes in the EMG activity of the abdominal musculature and in the intraballoon manometric recordings, with a significant increase in both parameters when compared with their respective basal activities (Figures 1a and b). Moreover, intraballoon manometric recordings showed an increase over the CRD protocol: from the first to the 12th pulse, the response to CRD increased by 47��29% (n=12) (Figure 1b). On the other hand, the response to EMG was stable over the experimental time without changes in magnitude throughout the protocol (Figure 1a). Figure 1 Effects of oral pregabalin on the visceromotor responses to repetitive noxious colorectal distension (CRD; 80mmHg) in rats. Responses to CRD (12 distensions in 60min) were determined simultaneously in the same animals by electromyographical .
.. Pregabalin inhibited in a dose-related manner the responses to CRD, either assessed through EMG or through intraballoon manometric recordings. At 50��molkg?1, pregabalin reduced the overall response to CRD by 10��13% (P>0.05 vs vehicle) and 32��9% (P<0.05 vs vehicle) when assessing EMG and balloon pressure recordings, respectively. A further increase in the dose (200��molkg?1) resulted in a significant inhibition of both measurements compared with the response in vehicle-treated animals (EMG: 26��10%; intraballoon pressure: 50��5%; both P<0.05) (Figures 1c and d). A lower dose of pregabalin (10��molkg?1, p.o.) did not affect the responses to distension, although a tendency was observed when assessing intraballoon pressure recordings (16��7% inhibition, P=0.079 vs vehicle) (Figures 1c and d). Effects of pregabalin on visceromotor responses to ascending phasic CRD During ascending phasic CRD (10�C80mmHg), vehicle-treated animals showed a simultaneous pressure-related increase in EMG activity of the abdominal musculature Dacomitinib and in the intraballoon manometric recordings. Pregabalin (200��molkg?1, p.o.