Determinants of Pain Onset in the Third Molar Model

Method:  We conducted a secondary analysis of pooled data from 448 patients enrolled in two randomised, double-blind, parallel-group phase III multicentre clinical trials investigating the efficacy and tolerability of a novel s.c. diclofenac formulation (Akis®, IBSA Institut Biochimique SA, Switzerland, ClinicalTrials.gov Identifier numbers: NCT00942448 / NCT00943098). Following single-sided third molar removal, patients were randomised when they developed moderate-to-severe pain (≥50mm on VAS) within 6 hours after surgery. Multiple linear regression was used to evaluate determinants of time until onset of pain (TOP) from first local anaesthesia.

Result:  Mean TOP was 185 minutes (range 40 min – 358 min). Study centre was the strongest predictor of TOP (mean TOP ranging between 150 min and 209 min). Women experienced pain 15 minutes earlier than men on average (p=0.003). There was a trend for later pain onset with increasing BMI (underweight: 180 min, normal: 183 min, overweight: 186 min, obese: 195 min, p for trend=0.076) and less bone removal (minor: 191 min, moderate: 185 min, severe: 176 min, p for trend=0.084). No independent association was found between age, smoking, local anaesthetic dose, duration of surgery, lingual flap and tooth sectioning.

Conclusion:  Female gender, more invasive surgery and lower BMI may be associated with earlier onset of moderate-to-severe pain in the third molar pain model. However, study centre was a stronger predictor of TOP than any of the patient characteristics studied. No other patient- or surgery-related factors showed significant influence on pain onset following third molar surgery.