Background: bunionectomy has been used as a model of postoperative pain for opioids and nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors with a fast onset of analgesia. The present study was conducted to assess whether the utility of the model can be broadened in assessing the efficacy of analgesics with diverse mechanisms and pharmacokinetic profiles in drug development and to enhance the sensitivity of a bunionectomy model.
Methods: this was a single center, randomized, double-blind, placebo-controlled, three-arm, parallel group methodology study to evaluate the effects of pregabalin and naproxen sodium on postoperative pain following bunionectomy. Patients (n=100) were randomized 1:1:1 to three treatments (administered 1 hour before and at defined intervals after surgery): pregabalin 300 mg before surgery and 150 mg every 8 hours; naproxen sodium 550 mg before surgery and 550 mg every 12 hours; or placebo in a double-dummy fashion. Primary endpoints were patient-controlled analgesic (PCA) hydromorphone consumption and the time to first PCA hydromorphone use postsurgery over 24 hours.
Results: of the 100 patients randomized, 96 completed the study. Relative to placebo, pregabalin and naproxen sodium, respectively, reduced PCA hydromorphone consumption by 51% (P=0.005) and 65% (P<0.001) and increased the median time to first use of PCA hydromorphone by 1.5 hours (P=0.004) and 3.7 hours (P<0.001). Both drugs significantly (P<0.050) decreased use of oral opioid rescue medication over 24-48 hours postsurgery relative to placebo. Although there were no statistically significant differences between naproxen sodium and pregabalin in opioid consumption and global evaluation of medication, overall naproxen sodium appeared to be more effective at reducing pain.
Conclusions: the model provided a sensitive method for evaluating efficacy of compounds with diverse mechanisms and pharmacokinetic profiles. The robustness of the enhanced pain model renders bunionectomy pain a valuable tool to assess novel analgesic compounds in small numbers of subjects early in drug development.