TY - JOUR
T1 - Hyperalgesia and Persistent Pain after Breast Cancer Surgery
T2 - A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition
AU - van Helmond, Noud
AU - Steegers, Monique A
AU - Filippini-de Moor, Gertie P
AU - Vissers, Kris C
AU - Wilder-Smith, Oliver H
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Breast Neoplasms/drug therapy
KW - Celecoxib/therapeutic use
KW - Cyclooxygenase 2 Inhibitors/therapeutic use
KW - Double-Blind Method
KW - Female
KW - Humans
KW - Hyperalgesia/drug therapy
KW - Isoxazoles/therapeutic use
KW - Mastectomy/adverse effects
KW - Mastectomy, Segmental/adverse effects
KW - Middle Aged
KW - Pain Measurement
KW - Pain Threshold/drug effects
KW - Pain, Postoperative/drug therapy
KW - Perioperative Period
KW - Prospective Studies
KW - Quality of Life
KW - Surveys and Questionnaires
KW - Treatment Outcome
U2 - 10.1371/journal.pone.0166601
DO - 10.1371/journal.pone.0166601
M3 - Article
C2 - 27935990
VL - 11
SP - e0166601
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 12
ER -