Postoperative pain is a major cause of postoperative suffering, prolonged hospitalization, complications and increased costs. It has been shown that postoperative pain is a frequent and unresolved problem in Norwegian hospitals, and so also internationally. Building knowledge on pain prophylaxis and treatment of postoperative pain is an area with substantial potential for improvement and affecting many patients.~Opioids remain as first-line drugs for the treatment of moderate to severe postoperative pain, but the use is limited by well-known side-effects, most of which are dose-dependent.~The opioid oxycodone is used as standard therapeutic treatment for acute postoperative pain, either in immediate-release formulation, OxyNorm®, or as extended-release formulation, OxyContin®. Oxycodone is a pure opioid receptor agonist with central and peripheral effects.~Tapentadol hydrochloride/depot (Palexia/depot®) is a novel, centrally acting, strong analgesic with a dual mechanism of action. It is a µ-opioid receptor agonist with central and peripheral effects, and it also inhibits noradrenaline reuptake in the central nervous system. Tapentadol is an active compound, devoid of active metabolites and not reliant on enzyme systems. For these reasons, it has a low drug interaction potential.~Opioid receptors are usually not well expressed in non-inflamed peripheral tissue and they have limited effect on the peripheral pathophysiology and origin of acute wound pain. While postoperative pain basically is induced by relevant nociceptive pain nerve stimulation, there is also a neuropathic component in most cases. Opioids are not very effective in blocking neuropathic pain in low to moderate doses. Also, opioids do not have the potential to block the wind-up of pain when given before the start of surgical trauma. The noradrenaline re-uptake inhibition (NRI) component of tapentadol is believed to have effect on descending pathways in the spinal cord. Such excitatory and inhibitory pathways act through monoamine systems mediated by noradrenaline and 5-hydroxytryptamine (5-HT). The inhibition of noradrenaline reuptake increases monoaminergic transmission in the descending pain inhibitory pathways, leading to reduced pain sensation. It seems like tapentadol produce not simply additive, but synergistic anti-nociceptive action by inhibitory actions in µ-opioid receptor agonism and NRI. While the effect on µ-opioid receptors is important in nociceptive pain, the NRI component seems to be especially relevant for both acute and persistent neuropathic pain.~Tapentadol has been shown effective in models of acute, osteoarthritic, neuropathic and cancer-induced bone pain. There is now an increasing use of tapentadol in postoperative pain treatment in Norwegian hospitals. However, there is a lack of broad-based evidence for the use of tapentadol in the post-surgical setting. So far, to our study group's knowledge, there are only published studies on postoperative pain treatment after orthopedic and dental surgery, but none related to visceral pain. Most studies have so far been initiated by the industry. The standard treatment today, oxycodone, on the other hand is shown in several studies to have a preferable analgesic effect on pain of visceral origin compared to morphine.~The synergistic effect of µ-opioid receptor agonism and NRI translates clinically into less adverse effects than with pure opioid agonists. This is probably due to less µ-opioid receptor stimulation. Tapentadol is shown in several studies on chronic pain patients to have comparable analgesic effects to traditional opioid pain medications like oxycodone and morphine, but with a more tolerable side-effect profile. In the postoperative setting after dental or orthopedic surgery, studies have shown less nausea and constipation. It has also been suggested a lower frequency of pruritus compared with oxycodone, but no difference in central nervous system symptoms such as somnolence or dizziness. The most dangerous side-effect from opioids is respiratory depression with the potential of fatal outcome. Intravenous oxycodone is shown to have dose dependent effect on respiratory depression decreasing the mean minute volume with a more rapid onset than morphine. One study has attempted to study respiratory depression after tapentadol administration, but failed due to technical failure of the pulse oximetry device. The investigators have not found any other publications from short-term postoperative pain management comparing any respiratory effect of tapentadol to the traditional opioids.~The aim of the study is to compare the analgesic effect and side-effects of this new analgesic, tapentadol, to the standard treatment to day, oxycodone, in the acute postoperative period in patients with visceral pain. Patients scheduled for elective hysterectomy are chosen as the study population, as this is a group of patients with significant visceral pain after surgery.~The study will be performed as a randomized, double-blind, prospective, parallel-group, single-center study on patients scheduled for laparoscopic sub-/total hysterectomy, as this is a classic study comparing effects from two different medications on two groups in a population.
Opioids remain the first-line drugs for the treatment of moderate to severe postoperative pain, but the use is limited by well-known side-effects, most of which are dose-dependent.~The opioid oxycodone is standard therapeutic treatment for acute postoperative pain, either in immediate-release formulation, OxyNorm®, or as extended-release formulation, OxyContin®. Oxycodone provides analgesic effects through µ-opioid receptors in the central nervous system.~Tapentadol hydrochloride/depot (Palexia/depot®) is a novel, centrally acting, strong analgesic with a dual mechanism of action on µ-opioid receptors and noradrenaline reuptake in the central nervous system. Tapentadol is an active compound, devoid of active metabolites and not reliant on enzyme systems. For these reasons, it has a low drug interaction potential. This dual mechanism also translates clinically into less adverse effects than with pure opioid agonists like oxycodone. This is probably due to less µ-opioid receptor stimulation.~Tapentadol has been shown effective in models of acute, osteoarthritic, neuropathic and cancer pain. There is now an increasing use of tapentadol in postoperative pain treatment in Norway. However, there is a lack of broad-based evidence for the use of tapentadol in the post-surgical setting. So far, to our knowledge, there are only published studies on postoperative pain treatment after orthopedic and dental surgery, but none related to deep abdominal pain.~Tapentadol is shown in several studies on chronic pain patients to have comparable analgesic effects to traditional opioid pain medications like oxycodone and morphine, but with a more tolerable side-effect profile. In the postoperative setting after dental or orthopedic surgery, studies have shown less nausea and constipation. It has also been suggested a lower frequency of pruritus compared with oxycodone, but no difference in central nervous system symptoms such as sleepiness or dizziness. The most dangerous side-effect from opioids is respiratory depression with the potential of fatal outcome. The investigators have not found any publications from short-term postoperative pain management comparing the respiratory effect of tapentadol to the traditional opioids.~The aim of the study is to compare the analgesic effect and side-effects of this new analgesic, tapentadol, to the standard treatment to day, oxycodone, in the acute postoperative period after hysterectomy.