title: The neurological safety of epidural parecoxib in rats.
abstract: Epidural injection of cyclooxygenase-2 inhibitors has been suggested as a useful therapeutic modality in pain management in animal studies and clinical settings. Direct epidural administration of parecoxib, a highly selective cyclooxygenase-2 inhibitor, may have advantages over its parenteral administration regarding required dose, side effects, and efficacy. However, no animal studies have been performed to investigate the possible neurotoxicity of epidurally injected parecoxib. Therefore, the present study was performed to assess the neurotoxicity of epidurally injected parecoxib in rats. Rats (n=45) were randomly divided into three groups: normal saline group (group N, n=15), ethanol group (group E, n=15), and parecoxib group (group P, n=15). 0.3 mL of epidural parecoxib (6 mg) and the same volume of epidural ethanol or normal saline were injected into the epidural space. Neurologic assessment was performed 3, 7 and 21 days after the injection by pinch toe testing. Histologic changes were evaluated for vacuolation of the dorsal funiculus, chromatolytic changes of the motor neurons, neuritis, and meningeal inflammation. All rats in groups N and P showed normal response to pinch-toe testing and had a normal gait at each observation point. Histological examination showed no evidence suggestive of neuronal body or axonal lesions, gliosis, or myelin sheet damage in group N or P at any time. However, all rats in group E showed sensory-motor dysfunction, behavioral change, or histopathological abnormalities. No neurotoxicity on the spinal cord or abnormalities in sensorimotor function or behavior was noted in rats that received epidural parecoxib.
authors.affiliation: Department of Anesthesiology, National Cancer Center, Goyangsi, Republic of Korea.
authors.forename: Yang Hyun
authors.initials: YH
authors.lastname: Kim
authors.forename: Pyung Bok
authors.initials: PB
authors.lastname: Lee
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Park
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Lim
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Wonsik
authors.initials: W
authors.lastname: Ahn
mesh_terms: D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000633:toxicity; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005684:Gait / Q000187:drug effects; D007268:Injections, Epidural; D007555:Isoxazoles / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D009460:Neurologic Examination; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D000431:Ethanol; C409945:parecoxib