Pharmacological modulation of experimental phasic and tonic XXXX by @entity1286 , @entity680 and @entity3652 in healthy volunteers.

@entity1 @entity1024 @entity1009 @entity680 @entity3652 @entity143 @entity1286 @entity158 @entity925 @entity1363
BACKGROUND: @entity925 is a major clinical problem but the underlying mechanisms and its pharmacological modulation need further investigation. This study on 15 volunteers evaluates if two experimental @entity925 models are sensitive to micro -receptor agonists and to an @entity1024 ( @entity143 )-receptor antagonist. METHODS: In the left tibialis anterior, intramuscular electrical (IMES) @entity158 thresholds were determined for single (SPTmuscle) and five (RPTmuscle) repeated stimuli. Also @entity158 to suprathreshold stimulation at 150% of RPTmuscle, 10 s, was assessed on a visual analog scale (VAS) as AUCimes (area under the VAS curve). In the right TA muscle, @entity158 intensity on infusion of 0.5 ml of hypertonic saline, 5% (AUCsaline) and @entity158 distribution indicated as local and referred were evaluated. @entity158 variables were assessed before, during and after intravenous infusions of @entity1286 (10 microg x kg-1 @entity1009 , 10 min), @entity680 (target-controlled infusion, plasma concentration; 60 ng ml-1, 60 min) and @entity3652 (10 microg x kg-1 @entity1009 , 60 min). All data were normalized to baseline @entity158 values (before drug infusions were initiated) and compared with placebo ( @entity1363 , 2 microg x kg-1 @entity1009 , 10 min). RESULTS: SPTmuscle increased (log mean values +/- SD, mA) with @entity1286 (0.11 +/- 0.17, P < 0.05), @entity680 (0.28 +/- 0.24, P < 0.001) and @entity3652 (0.19 +/- 0.18, P < 0.01) as compared with placebo (-0.03 +/- 0.12). @entity680 and @entity3652 also increased RPTmuscle (0.25 +/- 0.21, P < 0.01 and 0.21 +/- 0.19, P < 0.05, respectively) as compared with placebo (0.00 +/- 0.17). @entity158 to IMES (AUCimes) was reduced (median values [25th-75th percentiles], cm x s) by @entity680 and @entity3652 (-19.7 [-14.6 - -29.6] and-12.8 [-8.3 - -27.8], P < 0.05, respectively) vs. placebo (-0.8 [1.6 - -12.3]). Similar drug effects were seen when @entity158 to infusion of hypertonic saline (AUCsaline) was assessed ( @entity680 :-388 [-99 - -677] and @entity3652 :-326 [-227 - -573], P < 0.05 compared with placebo: 150 [449--240]). @entity3652 also reduced the size of the @entity158 area (-58.4 [-21.2 - -176.1], < 0.05) as compared with placebo (-0.4 [70.6 - -13.4]). The frequency of @entity158 was also lower when @entity3652 was given (3/13, P < 0.05) vs. placebo (9/14). CONCLUSION: The study demonstrates that experimental @entity925 induced in @entity1 by electrical stimulation and infusion of hypertonic saline is sensitive to pharmacological modulation similar to preclinical animal tests and clinical trials. The data suggest that these models can be valuable tools in analgesic drug development.
