Analgesic effects of propofol on acute postoperative pain and the underlying mechanisms

Abstract

Acute postoperative pain management remains unsatisfactory and is associated with many negative clinical outcomes. Propofol, used for induction and maintenance of general anesthesia may help to alleviate pain after surgery. In this thesis, I started by a systematic review and meta-analysis to identify studies reporting the postoperative analgesic effects of propofol for general anesthesia and its opioid sparing effect in comparison with other inhalational anesthetics. Fourteen trials met inclusion criteria and were included. No significant difference in pain scores at 2 hours postoperatively was found. Propofol was however associated with a statistically significant albeit marginal reduction in pain scores at 24 hours postoperatively. Data was insufficient to show a difference regarding 24 hours morphine-equivalent. Propofol was also associated with reduction in postoperative nausea and vomiting (PONV). Another retrospective study that explored patients undergoing liver surgery between 2010 and 2013. Patients using total intravenous anesthesia with propofol (TIVA group) reported statistically significantly less pain during coughing on postoperative day 1 and 2 but not 3, comparing pain patients receiving sevoflurane (sevoflurane agent). TIVA group also consumed significantly less daily, accumulative and total dose of morphine when compared with sevoflurane group. However, there was no differences in total duration of intravenous patient controlled analgesia (PCA) morphine use. No difference was found in terms of side effects and patients’ satisfaction. The mechanism under pain reliving effect of propofol remains elusive. Therefore, I investigated the mechanisms of the analgesic effects of propofol in rats using an inflammatory pain model and a postoperative pain model. In the formalin induced inflammatory pain model, preventive analgesic effects of propofol was studied. Intravenous propofol was given for 1 hour and followed by either 30 min or 2 h recovery time before formalin injection into hind paw. Compared with the control group, propofol decreased the pain score in the late phase of formalin test. Moreover, preventive propofol diminished activation of spinal GluN2B receptors and Erk1/2 induced by formalin. Propofol also inhibited Ca2+ influx mediated by NMDA receptors in SH-SY5Y cells. There was no difference in activity of p38 and JNK among each group. I next explored whether propofol also affected postoperative surgical pain in a model of hind plantar incision. I found that rats anesthetized with propofol had less postoperative pain compared with intralipid within 2 hours after the surgery. Propofol decreased the activity of GluN2B receptors in the c-fos positivity neurons in the ipsilateral spinal cord dorsal horn. P38, rather than JNK and Erk, was involved in this signaling pathway. All the results suggest that preventive analgesic effect in inflammatory pain and pain relieving effect of acute postoperative pain using propofol are promising. GluN2B receptor in the spinal cord dorsal horn may be the key target of propofol for its analgesic effects after surgery.