The root canals of 588 consecutive nonsurgical patients with varying levels of pain were completely instrumented in 10 endodontic practices and 4 endodontic graduate programs. The participants were sequentially assigned to one of nine medications and a placebo. The severity of pain was assessed by the visual analog scale for 72 h following instrumentation. Among all of the parameters studied, three factors (preoperative pain, apprehension, and types of medication) were found to be significant in determining postinstrumentation pain. An association was found between the intensity of pre-and postoperative pain. As the intensity of preoperative pain increased, the chances for more severe postoperative pain increased (p < 0.0001). In addition, an association between the presence of apprehension before any treatment and postoperative pain was also noted (between 0.012 < p < 0.047). Examination of the time-effect curves for various medications in patients with no mild pain showed no statistical significant difference between the effectiveness of different medications and placebo. However, a multiple comparison of the effectiveness of various medications and placebo on patients in moderate and severe preoperative pain showed that ibuprofen, ketoprofen, erythromycin base, penicillin, and methylprednisolone plus penicillin were more effective than placebo within the first 48 h following complete instrumentation.

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