Shientag, L. J. 2016. Efficacy of common analgesics for postsurgical pain in rats. JAALAS 55(1), 7.

I have some comments about the use of ketoprofen for analgesia in rats discussed in the recent JAALASarticle by Waite and colleagues.3 One of the conclusions reached by the authors was that, for postsurgical pain, “ketoprofen was effective when given prophylactically (Figure 5B) at the 15 mg/kg (P<0.01) and 25mg/kg (P<0.05) doses” (rat grimace scale analysis).3 The designated chart (Figure 5B) includes 10 mg/kg and 25 mg/kg doses, but not the stated 15 mg/kg dose, so it appears to contain an error. But all of these doses are too high. Shientag and colleagues previously revealed that a single 5 mg/kg SC dose of ketoprofen caused significant bleeding, erosions, and ulcers in the gastrointestinal (GI) tracts of anesthetized and nonanesthetized rats by 24 h postadministration compared to saline controls.2 It is not clear why much higher doses of ketoprofen would be tested in rats for post-operative analgesia when the 5 mg/kg dose caused significant GI lesions in most of the test animals in the aforementioned study. Although the Shientag study used Sprague-Dawley rats, the incontrovertible evidence of GI toxicity would seem to extend to all rat stocks and strains until proven otherwise. The analgesic effects of ketoprofen are expected to last 24 h and it is usually given once a day for postop pain in many species.1 The information provided in the Waite study indicates that the prophylactic treatment group of rats was tested at only one time point, around 110 minutes post ketoprofen administration (estimating 20 min duration for surgery). However, it can be realistically assumed that most researchers using ketoprofen for pain management would require a longer survival period and duration of pain management, at least up to 24 h, and could see serious GI toxicity by then. The findings of Shientag and colleagues strongly suggest that ketoprofen should have been omitted from the Waite and colleagues study. Its therapeutic use for pain management should no longer be recommended in rats.