A new knee surgery model in rats to evaluate functional measures of postoperative pain

With the increase in the number of total knee surgeries being performed, postoperative analgesic management remains a challenge. We used a new animal knee surgery model to characterize pain-related behavior in the rat, and its therapeutic modulation with systemic and intrathecal drug treatment.

Rats were anesthetized with isoflurane and an incision was made over the left knee to expose the patella tendon. The tendon was reflected aside and a 1.4-mm diameter, 0.5 mm deep hole was drilled in both the femur and tibia at 2 mm above and below the knee joint, respectively. The holes were filled with dental cement and the wound was closed. Sham surgery animals only had a skin incision. Some animals had previously been implanted with a lumbar intrathecal catheter for drug injection. At 24 h after surgery, animals received the following drugs systemically: i.p. morphine sulfate 0.3-1 mg/kg, i.p. ketorolac 2.5-20 mg/kg, p.o. celecoxib 10-50 mg/kg, i.p. ketamine hydrochloride 2.5-10 mg/kg, i.p. clonidine hydrochloride 25 microg/kg, p.o. pregabablin 10-20 mg/kg, or drug vehicle; or intrathecally: morphine sulfate 0.3-1 microg, ketorolac 4-80 microg, L-745,337 80 microg, pregabalin 15 microg, neostigmine 0.5 microg, or saline vehicle. Pain-related behavior was then assessed by recording exploratory spontaneous activity, in which vertical and horizontal light beam interruptions were automatically recorded to measure rearing activity and ambulation for 60 min. Data were compared using analysis of variance with the Tukey-B post hoc test.

The model demonstrated deficits in rearing and ambulation compared with sham skin incision control animals on postsurgery days 1-3. Systemic and intrathecal morphine improved rearing and ambulation, with knee surgery/ morphine rats displaying as much activity as sham skin incision/vehicle animals, whereas knee surgery/vehicle rats showed decreased activity. Systemic ketorolac 20 mg/kg improved rearing and ambulation, with knee surgery/ketorolac rats showing increased activity compared with knee surgery/vehicle animals. Intrathecal ketorolac 4-40 microg did not increase rearing or ambulation, but the 80 microg dose was effective. Other drugs tested, systemically or intrathecally, did not restore activity to normal levels.

This study presents a new simple, reproducible rat model to assess function and discomfort after knee surgery, and one that responds to therapeutic interventions. In this knee surgery model, both systemic and intrathecal administration of either morphine or ketorolac caused reversal of the deficits in rearing and ambulatory behavior at 24 h postsurgery.