Upregulation of 15-Hydroxyprostaglandin Dehydrogenase by Celecoxib to Reduce Pain After Laparoendoscopic Single-Site Surgery (POPCORN Trial): A Randomized Controlled Trial
<b>Background</b>: Peritoneal stretching from CO<sub>2</sub> insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on post...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1784 |
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| Summary: | <b>Background</b>: Peritoneal stretching from CO<sub>2</sub> insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on postoperative pain reduction and associated changes in peritoneal gene expression after laparoendoscopic single-site (LESS) surgery for benign gynecologic disease. <b>Methods</b>: In this randomized, double-blind, placebo-controlled pilot study, 70 patients were randomly assigned to receive either celecoxib or placebo (400 mg) 40 min before surgery. Peritoneal tissues were collected before and after CO<sub>2</sub> insufflation. We analyzed changes in expressions of prostaglandin I<sub>2</sub> synthase, prostaglandin E synthase (<i>PTGES</i>), <i>PTGES3</i>, aldo-keto reductase family 1 member C1, and 15-hydroxyprostaglandin dehydrogenase (<i>HPGD</i>). Numeric Rating Scale (NRS) pain scores were also compared between groups. <b>Results</b>: A total of 62 patients completed the study: 30 in the celecoxib group and 32 in the placebo group. The mean CO<sub>2</sub> exposure time was 60.4 min. In a quantitative real-time polymerase chain reaction analysis, <i>HPGD</i> mRNA expression significantly increased after surgery in patients exposed to CO<sub>2</sub> for more than 60 min. Patients treated with celecoxib showed a significantly higher rate of grade 3 expression (83.3% vs. 37.5%; <i>p</i> = 0.01) and a level 2 increase in <i>HPGD</i> expression on in situ hybridization (58.3% vs. 12.5%; <i>p</i> = 0.01), despite no significant difference on immunohistochemistry. Moreover, celecoxib effectively reduced NRS pain scores compared to placebo. <b>Conclusions</b>: In this pilot study, celecoxib appeared to reduce postoperative pain and was associated with increased HPGD mRNA expression in the peritoneal tissue of patients with prolonged CO<sub>2</sub> exposure during LESS surgery. These exploratory findings warrant confirmation in larger trials with functional validation of HPGD expression (ClinicalTrials.gov, NCT03391570). |
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| ISSN: | 2227-9059 |