Local Drug Infiltration Analgesia During Knee Surgery to Reduce Postoperative Pain in Rats

Reg Anesth Pain Med. 2016 May-Jun;41(3):374-9. doi: 10.1097/AAP.0000000000000353.


Background and objectives: There is increasing interest in local infiltration analgesia (LIA) to reduce postoperative pain with knee surgery. Despite widespread use of LIA, wide variations in drug combinations, infiltration techniques, and the concomitant use of systemic analgesics have made it difficult to determine the optimal drug combination for LIA.Using a previously validated animal knee surgery model, we aimed to determine the optimal combination of medications to reduce postoperative pain, and the best anatomical location and timing for local drug injection during surgery.

Methods: Knee surgery was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, dexamethasone, and morphine were injected around the knee and compared to saline placebo. Similar medications were injected systemically as a comparator group. Postoperative pain was assessed by measuring spontaneous rearing activity. Injections were given after bone drilling and/or just before wound closure.

Results: The 3-drug LIA combination of bupivacaine, ketorolac, and dexamethasone increased rearing (decreased pain) at 2 hours (P = 0.0198) and 24 hours (P = 0.0384) postsurgery compared to saline. The same drugs injected systemically had no effect. The ketorolac/dexamethasone combination for LIA was also effective at 2 hours (P = 0.0006) and 24 hours (P = 0.0279), and ketorolac alone reduced pain at 2 hours (P = 0.0045). Bupivacaine alone was less effective, and the addition of morphine had no effect. The 3-drug combination infiltrated just after creating holes in bone was more effective than when given into the wound just before wound closure.

Conclusions: Our animal study suggests that clinical trials with LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid might be useful for reducing postoperative pain after knee surgery, with the nonsteroidal anti-inflammatory drug having the greatest effect.Perioperative physicians should consider delivering LIA earlier during the procedure as opposed to solely at the time of wound closure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia / methods*
  • Analgesics, Opioid / administration & dosage*
  • Anesthetics, Local / administration & dosage*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Arthralgia / diagnosis
  • Arthralgia / etiology
  • Arthralgia / prevention & control*
  • Behavior, Animal / drug effects
  • Bupivacaine / administration & dosage*
  • Dexamethasone / administration & dosage*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Exploratory Behavior / drug effects
  • Injections
  • Joints / surgery*
  • Ketorolac / administration & dosage*
  • Male
  • Morphine / administration & dosage*
  • Motor Activity / drug effects
  • Pain Measurement
  • Pain, Postoperative / diagnosis
  • Pain, Postoperative / etiology
  • Pain, Postoperative / prevention & control*
  • Rats, Sprague-Dawley


  • Analgesics, Opioid
  • Anesthetics, Local
  • Anti-Inflammatory Agents
  • Morphine
  • Dexamethasone
  • Bupivacaine
  • Ketorolac