A Randomized, Double-blind, Placebo-controlled Trial on the Prevention of Chronic Postoperative Pain after Inguinal Hernia and Knee Surgery by Postoperative Treatment with Tapentadol

Rationale: The development of chronic postoperative pain is not well understood. We recently conducted a large trial in patients who underwent inguinal hernia surgery and investigated whether the pre-operative state of the endogenous pain modulatory system (a central pain modulatory system important for normal pain perception) could predict the development of postoperative chronic pain after inguinal hernia surgery. In this study we demonstrated that a normal functioning endogenous pain modulatory system was predictive for the development of postoperative chronic pain. Tapentadol is an analgesic able to influence the endogenous pain system by maintaining its function and we hypothesize that treatment with tapentadol will reduce the change to develop postoperative chronic pain.
Objective: To prevent the development of chronic postoperative pain after inguinal hernia surgery and knee replacement surgery and to further explore the mechanism behind the development of chronic postoperative pain.
Study design: A double-blind, randomized, placebo-controlled, non-crossover longitudinal study.
Study population: Patients planned for elective inguinal hernia surgery or knee replacement surgery.
Intervention (if applicable): Postoperative treatment with oral tapentadol sustained release (maximum of 100 mg twice daily) and placebo.
Main study parameters/endpoints: (1) The effect of tapentadol compared to placebo on the development of chronic pain in the first year after surgery; (2) The influence of the pre-operative pain profile on the development of chronic postoperative pain and (3) The influence of tapentadol and placebo on the individual pain profiles and its influence on the development of chronic postoperative pain.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden for the patients is that they will take low doses of pain medication for 1 month after surgery and will come to the hospital 2 times for pain testing and questionnaires. The hospital visit will take about 30-45 minutes.

We hypothesize that treatment with Tapentadol will reduce the development of chronic postoperative pain by enhancing or maintaining CPM responses and possibly reducing central sensitization. We hypothesize that a 4-week treatment with Tapentadol will reduce the risk for these patients to develop chronic postoperative pain in the first year after surgery.

After the treatment period the development of chronic pain will be assessed by telephone at 3, 6 and 12 months after the surgery. Pain intensity will be assessed using the numerical rating scale (NRS) and patients will be asked to fill in a pain diary every month where they score the average pain score during rest and during exercise in the last month and last week.

Tapentadol or placebo for a 4-week period