Effects of single and combination dosage regimens of ketorolac and dexmedetomidine on allodynia and nociception in rat model of osteoarthritis: an animal multi-group trial

INTRODUCTION: Ketorolac is a non-steroidal anti-inflammatory drug (NSAID), commonly used for acute pain relief. Dexmedetomidine is a highly selective alpha-2-adrenergic receptor agonists with an analgesic effect. Although, ketorolac and dexmedetomidine are effective individually, their combination effects have been studied less widely, specially in osteoarthritis (OA) nociceptive models in rats. METHODS AND MATERIALS: In this randomized animal study, OA was induced in healthy male Sprague-Dawley rats by intra-articular mono-iodoacetate (MIA). The animals were divided into six groups. The first group received no injection and served as control group. MIA was administered intra-articularly to the remaining five groups. The vehicle group received intraperitoneal injection of normal saline. The four treatment groups received intraperitoneal injection of ketorolac (5 mg/kg), ketorolac (10 mg/kg), dexmedetomidine (5 µg/kg), and a combination of ketorolac and dexmedetomidine (5 mg/kg and 5 µg/kg, respectively). Analgesic and allodynia responses were measured using behavioural tests including the von Frey, hot plate and formalin tests at various time intervals after administration. RESULTS: The von Frey test showed significant differences between the groups at 60 and 120 min. The paw withdrawal threshold was significantly higher in the ketorolac and ketorolac plus dexmedetomidine groups than in the vehicle group. Our investigation indicated significant differences in the mean responses between vehicle group and ketorolac and ketorolac plus dexmedetomidine groups at 60 min in hot plate test. Also, the combination of ketorolac and dexmedetomidine significantly reduced the pain score compared to the vehicle group in the second phase of the formalin test. CONCLUSION: The present study indicated that the co-administration of ketorolac and dexmedetomidine provides higher and longer-lasting analgesia effects than administration of ketorolac and dexmedetomidine individually in the rat model of OA-induced nociceptive. Further studies are needed to elevate dosing and evaluate adverse effects.