Comparison of the clinical and neurotoxic effects of diclofenac and ketorolac given intrathecally in rabbits

Abstract

Intrathecal (IT) drug administration is commonly used in the treatment of acute or chronic pain, and during anesthesia. This study investigates the neurotoxicity and behavioral changes associated with intrathecal administration of ketorolac and diclofenac in rabbits. Fifty New Zealand rabbits were divided randomly into five groups. 2% Evans Blue, 5 ml/kg, was given intravenously to all animals. Five hours later, we injected into the atlanto-occipital space 0.3 ml saline (control), 8–10 mg/kg and 24–30 mg/kg ketorolac (Ketorolac groups 1 and 2) and 1 mg/kg and 3 mg/kg diclofenac (Diclofenac groups 1 and 2). Blood pressure, heart rate, respiratory rate, urinary excretion, arterial blood gases and behavioral changes were monitored immediately and after vascular cannulation, after the injection of Evans Blue, and at three and 60 min after spinal injection. The hot plate test was performed five times. Appetite and aggression were followed until the 7th day, when the spinal cord was removed, and sections were taken from cervical, thoracic and lumbar levels. The sections were dyed with hematoxylin and eosin, and histopathological neurotoxicity scores determined by light microscopy. Blood-brain barrier scores were determined by immunofluorescence microscopy. The histology suggests that intrathecal diclofenac and ketorolac are neurotoxic. summary