Abstract 381 Developmental Pharmacology: Drug Effects on Neonatal Angiogenesis and Vascular Function Platform, Monday, 5/3

Introduction: Ketorolac(K) is one of the most potent NSAID's available for clinical use. Its analgesic efficacy is comparable to that of morphine(M) and in adults and older children it has been shown to be safe, with minimal side effects. In adults, ketorolac reduces the need for opioids in management of post-operative pain, thus avoiding the side effects of opioids such as sedation, respiratory depression, hypotension, addiction and dependence. However the effects of ketorolac have not been studied in neonatal animals or humans.

Hypothesis: Ketorolac is comparable to morphine in its analgesic effects in neonatal rats.

Methods: This was a blinded controlled study involving 128 rat pups divided into four groups: (a) K at 3 days, (b) K at 21 days, (c) M at 21 days. Each group received intraperitoneal saline or escalating doses of the test drug. Formalin was injected subcutaneously into the left hindpaw to produce acute pain and inflammation. 3 outcomes were assessed (i)Pain: After the formalin injection, pain was assessed over 1h using a behavioral scoring system. (ii)Inflammation: Left hindpaw diameter (h.d)was compared with right h.d which served as control (iii)Neural Response-Fos: 2 hrs after formalin injection, pups were infused using saline and paraformaldehyde, then the spinal cords were dissected, sectioned and stained for Fos using immunocytochemistry. The Fos staining was quantified to assess the neural response to pain.

Results: 1)Pain:K significantly reduced pain scores in 21 day old pups [P<0.01] but not the 3 day old pups. M produced a significant reduction in pain scores at both ages [P<0.01] 2)Inflammation: K reduced paw edema in 21 day old rats[P=0.04]. K at 3 days & M at both ages had no effect on paw diameter 3)Neural Response-Fos: 21 day rats treated with K had fewer Fos stained cells in their spinal cords compared to saline treated animals [P=0.055]. (Table)

Table 1 No caption available
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Conclusions: Ketorolac has a significant analgesic effect equivalent to that of morphine in 21 day old rat pups. It also has an anti-inflammatory effect at this age. At 3 days of age it does not have any significant effects on pain or inflammation. This study suggests that ketorolac may not be an effective analgesic at an immature stage of development, but may be more effective at a later stage of development.