Effects of different concentration of intrathecal doxepin on motor function and spinal cords ultramicrostructure in rats

Abstract

Objective To observe the effects of different concentration of intrathecal doxepin on motor function and spinal cords ultramicrostructure in rats, to evaluate the intrathecal (IT) doxepin spinal anesthesia and neurotoxicity in rats. Methods Thirty male Wister rats weighing 250-300 g were successfully implanted with microspinal catheters. Rats were randomly divided into two groups: normal saline group (group N, n=6) and doxepin group (group D), group D were divided into four subgroups: group D40, D20, D10 and D5 (n=6 for each group) to receive 40, 20, 10 and 5 mmol/L doxepin respectively. The motor function was evaluated before the drug administration (0 min) and 10, 20, 30 min, and then 30 min interval lasted for 6 h after administration by slope trial and modified Tarlov score, then rats were sacrificed, the lumbar segment of the spinal cord was removed for microscopic examination. Results The blockage of motor function in group D10 and D20 were significantly heavier than that before administration in 10-60 min and 10-90 min respectively (P<0.05), while 5 mmol/L doxepin produced only partial never block but group D40 could not full recovery in 6 h. The severity of neuronal damage such as vacuolization, chromatin margination in nuclear, swelled mitochondrions, vacuolization, the separation of lamellar axon myelin and nuclear pyknosis even apoptotic body in nucleus were presented. Conclusions Intrathecal doxpin can produce dose-dependent spinal anesthesia and neurotoxicity. Key words: Doxepin; Intrathecal; Injection; Neurotoxicity