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

• Published in: PloS one 2016-12, Vol.11 (12), p.e0166601-e0166601
• Main Authors: van Helmond, Noud, Steegers, Monique A, Filippini-de Moor, Gertie P, Vissers, Kris C, Wilder-Smith, Oliver H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analgesics; Anesthesia; Anesthesiology; Arthritis; Biology and Life Sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - physiopathology; Breast Neoplasms - surgery; Cancer; Cancer surgery; Cancer therapies; Care and treatment; Celecoxib; Celecoxib - therapeutic use; Complications and side effects; COX-2 inhibitors; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase-2; Dosage and administration; Double-Blind Method; Drugs; Female; Genesis; Hospitals; Humans; Hyperalgesia; Hyperalgesia - drug therapy; Hyperalgesia - etiology; Inflammation; Inhibition; Isoxazoles - therapeutic use; Lumpectomy; Mastectomy; Mastectomy - adverse effects; Mastectomy - methods; Mastectomy, Segmental - adverse effects; Mastectomy, Segmental - methods; Medicine; Medicine and Health Sciences; Middle Aged; Motivation; Nervous system; Pain; Pain management; Pain Measurement; Pain perception; Pain Threshold - drug effects; Pain, Postoperative - drug therapy; Pain, Postoperative - etiology; Palliative care; Patients; Perioperative Period; Postoperative pain; Pressure; Prospective Studies; Quality of Life; Randomization; Risk factors; Sensory disorders; Sensory testing; Surgery; Surgical oncology; Surveys and Questionnaires; Thresholds; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166601

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. 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. 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