Parecoxib Sodium

After pancreaticoduodenectomy, perioperative neurocognitive disorders (PND) are a common complication. Parecoxib, a selective cyclooxygenase-2 inhibitor, is used for its analgesic and antiinflammatory effects, but its impact on postoperative anxiety and cognitive function is not clear.

The patients undergoing laparoscopic pancreaticoduodenectomy at the Second Hospital of Hebei Medical University were enrolled in the study from November 1, 2020 to September 30, 2022 in this randomized controlled trial. Patients were randomly divided into Group P who received 20 mg of parecoxib intravenously 10 minutes before anesthesia and at the end of surgery and Group C who received an equal volume of normal saline at the same times. Primary outcomes included the effect of parecoxib on anxiety, cognitive impairment, and postoperative intestinal function recovery, with the incidence of PND calculated using the Z -value method. Secondary outcomes included pain control, length of hospital stay, postoperative recovery, complication rates, and analgesic use.

80 patients were enrolled and randomly divided into 2 groups of 40 equally: there were no significant differences in postoperative flatus passage, defecation time, hospital stay, or complication rates ( P  > .05). In terms of postoperative anxiety, the experimental group had significantly lower State Anxiety Inventory scores at 24 hours postoperatively (T2) ( P  < .05). Cognitive function, measured by Montreal Cognitive Assessment scores, did not show significant differences; however, cognitive decline was less pronounced in the experimental group. PND rates were 5% (2/40) in the experimental group versus 12.5% (5/40) in the control group, suggesting a possible clinical tendency toward reduced incidence, although the difference did not reach statistical significance. The rates of PND at 24 hours (T2) and 7 days (T3) postoperatively were 10% (4/40) and 5% (2/40) for the experimental group, compared to 15% (6/40) and 12.5% (5/40) for the control group using the Z -value method, Although the between-group differences did not reach statistical significance, a lower incidence was observed in the parecoxib group, suggesting a possible clinical tendency.

Parecoxib, when used with pancreaticoduodenectomy, alleviates postoperative anxiety and neurocognitive disorders without affecting postoperative intestinal function recovery or increasing the incidence of postoperative complications.

Methamphetamine (METH) use produces lasting elevations in peripheral and central inflammation that correspond to cognitive and behavioral deficits, which may contribute to the likelihood of relapse. Though a great deal of research over the last few decades has attempted to investigate pharmacotherapies to help facilitate long term abstinence from METH, there are still no FDA approved medications to treat METH use disorders. Our laboratory recently showed that markers of neuroinflammation persist three weeks into abstinence following prolonged (96 h/week for 3 weeks) access to METH self-administration. We also showed that medial prefrontal cortex (mPFC) mediated behavioral flexibility deficits observed at this timepoint are attenuated by the COX-2 inhibitor parecoxib. Given the role of microglia in central inflammatory processes, the current work utilized immunohistochemistry to determine whether COX-2 expression in microglia was elevated in the mPFC during abstinence from METH. We also sought to determine if METH-induced changes in microglial morphology could potentially be altered by COX-2 inhibition. We found that the number of COX-2 expressing cells was elevated in the mPFC of rats that self-administered METH compared to those that self-administered saline. Surprisingly, COX-2 immunoreactivity was absent in microglia but was predominantly observed in neurons. Most COX-2 immunoreactivity was detected in glutamatergic neurons in both sexes, while males exhibited a reduction in COX-2 expression in GABAergic neurons. COX-2 immunoreactivity was frequently absent from the infralimbic and cingulate cortices and was therefore not analyzed. Paired with our prior findings that COX-2 inhibition attenuates METH-induced behavioral deficits known to be mediated by the mPFC, these results suggest that altered neuronal COX-2 expression should be investigated for its influence on METH-induced deficits in mPFC function.