Modified Indomethacin Enhances Pain Relief in Postsurgical Incision Pain Model

BALTIMORE, Md.—Pretreatment with indomethacin associated with phosphatidylcholine (INDO-PC) has both analgesic and anti-inflammatory effects without the gastrointestinal toxicity usually observed with the NSAID indomethacin, results of a postsurgical incision pain model have found.

Susan M. Carlton, PhD, and colleagues from the University of Texas Medical Branch, Galveston, recorded presurgical mechanical sensitivity in rats, who then received tail vein injections of 2 mg/kg INDO-PC (n=6), 2 mg/kg indomethacin (n=5), or vehicle (n=6). After being anesthetized with 2% isoflurane, a 1 cm incision was made in one hind paw and the wound closed.

Rats were monitored for acute drug effects by being retested for mechanical sensitivity at 20 minutes, 30 minutes, and 1, 2, 3, and 4 hours after surgery; flinching behavior signaled spontaneous pain. Daily over the next 7 days, body weight and paw size were recorded. Rats were also tested every morning, injected IV, and retested 2 hours following the injection. On day 7, rats were euthanized and blood was drawn to measure hematocrit. The gastrointestinal tract was removed and toxicity assessed.

In the first 24 hours and with daily treatment, pretreatment with 2 mg/kg INDO-PC resulted in significantly less mechanical sensitivity compared to INDO alone or vehicle. INDO-PC also significantly reduced spontaneous pain that developed following surgical incision. Daily injection of INDO-PC resulted in more potent analgesia during the week post surgery compared to INDO alone or vehicle. INDO-PC had a positive effect on weight maintenance following surgery. In contrast, INDO rats lost weight for the first 4 days following surgery.

All groups developed a similar amount of inflammation in the hind paw regardless of drug treatment. No gastrointestinal toxicity was evident in any group, the investigators reported during the American Pain Society's 29th Annual Scientific Meeting.