title: Curcumin treatment attenuates pain and enhances functional recovery after incision.
abstract: BACKGROUND
  Acute pain after surgery remains moderate to severe for 20% to 30% of patients despite advancements in the use of opioids, adjuvant drugs, and regional anesthesia. Depending on the type of surgery, 10% to 50% of patients experience persistent pain postoperatively, and there are no established methods for its prevention. Curcumin (diferuloylmethane) is one of the phenolic constituents of turmeric that has been used in Eastern traditional medicine as an antiseptic, antioxidant, anti-inflammatory, and analgesic agent. It may be effective for treating postoperative pain.
  
  
  METHODS
  We used the hindpaw incision model with C57BL/6 mice. Sensitization to mechanical and thermal stimuli as well as effects on edema and temperature were measured up to 7 days after surgery. Spontaneous pain after incision was assessed by using conditioned place preference (CPP), and alterations in gait function were assessed using multiparameter digital gait analysis.
  
  
  RESULTS
  Curcumin (50 mg/kg) significantly reduced the intensity of mechanical and heat sensitization after hindpaw incision in mice. No effects of curcumin on baseline nociceptive thresholds were observed. Curcumin also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. In addition, perioperative curcumin treatment attenuated hyperalgesic priming due to incision when mice were subsequently challenged with hindpaw prostaglandin E2 application. Furthermore, while vehicle-treated mice had evidence of spontaneous pain 48 hours after incision in the CPP paradigm, no evidence of ongoing pain was observed in the mice treated with curcumin. Likewise, hindpaw incision caused changes in several gait-related indices, but most of these were normalized in the curcumin-treated animals. The peri-incisional levels of several pronociceptive immune mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor α, and macrophage inflammatory protein-1α were either not reduced or were even augmented 1 and 3 days after incision in curcumin-treated mice. The anti-inflammatory cytokine IL-10 was unchanged, while transforming growth factor-β levels were enhanced under the same conditions.
  
  
  CONCLUSIONS
  Our studies suggest that curcumin treatment is effective in alleviating incision-induced inflammation, nociceptive sensitization, spontaneous pain, and functional gait abnormalities. Augmented transforming growth factor-β production provides one possible mechanism. These preclinical findings demonstrate curcumin's potential as a preventative strategy in postoperative pain treatment.
authors.affiliation: From the *Department of Anesthesia, Stanford University School of Medicine, Stanford, California; and †Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors.forename: Peyman
authors.initials: P
authors.lastname: Sahbaie
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Liang
authors.forename: Xiao-You
authors.initials: XY
authors.lastname: Shi
authors.forename: J David
authors.initials: JD
authors.lastname: Clark
mesh_terms: D059787:Acute Pain / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D001831:Body Temperature / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D018409:Foot Injuries / Q000150:complications / Q000188:drug therapy; D005684:Gait / Q000187:drug effects; D006614:Hindlimb / Q000293:injuries; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D020127:Recovery of Function / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D003474:Curcumin