Hyperalgesia and Persistent Pain After Breast Cancer Surgery: A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Dec 10

PMID 27935990

Citations 17

Authors

Noud van Helmond

Monique A Steegers

Gertie P Filippini-de Moor

Kris C Vissers

Oliver H Wilder-Smith

Affiliations

Soon will be listed here.

Abstract

Background: Persistent pain is a challenging clinical problem after breast cancer treatment. After surgery, inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain. Using quantitative sensory testing, we tested the hypothesis that adding COX-2 inhibition to standard treatment reduces hyperalgesia after breast cancer surgery. A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia.

Methods: 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were randomized to COX-2 inhibition (2x40mg parecoxib on day of surgery, thereafter 2x200mg celecoxib/day until day five) or placebo. Preoperatively and 1, 5, 15 days and 1, 3, 6, 12 months postoperatively, we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100mm VAS score for pain. We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication. To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months.

Results: 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis. Contrary to our primary hypothesis, change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo. COX-2 inhibition had an effect on pain on movement at postoperative day 5 (p<0.01). Consistent with our secondary hypothesis, change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain (p<0.01) from day 5 to 1 year postoperatively.

Conclusions: Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery. Central sensitization may play a role in the genesis of persistent postsurgical pain.

Citing Articles

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How to Modulate Peripheral and Central Nervous System to Treat Acute Postoperative Pain and Prevent Pain Persistence.

Cazzaniga S, Real G, Finazzi S, Lorini L, Forget P, Bugada D Curr Neuropharmacol. 2023; 22(1):23-37.

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Chronic postsurgical pain after minimally invasive adrenalectomy: prevalence and impact on quality of life.

van Helden E, van Uitert A, Albers K, Steegers M, Timmers H, dAncona F BMC Anesthesiol. 2022; 22(1):153.

PMID: 35590236 PMC: 9118616. DOI: 10.1186/s12871-022-01696-4.

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