Effects of intrathecal ketamine on synapsis remodeling in spinal dorsal horn during development of morphine tolerance in a rat model of neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of intrathecal (IT) ketamine on the synapsis remodeling in the spinal dorsal horn during devolopment of morphine tolerance in a rat model of neuropathic pain (NP). Methods Male SD rats weighing 200-250 g were used in this study. IT catheter was placed in the subarachnoid space according to Yaksh. Forty-eight SD rats in which IT catheter was successfully placed were randomly divided into 6groups (n=8 each): group sham operation (group S); group NP; group normal saline 20 μl IT(group NS);group morphine 20 μg IT (group M); group ketamine 50 μg IT (group K) and group morphine 20 μ g + ketamine 50 μg IT (group MK). NP was induced by compression of right L4,5 dorsal root ganglions with steel wire inserted through L4,5 intervertebral foramen in NP,M,K and MK groups. Normal saline or morphine and/or ketamine were injected IT once a day for consecutive 14 days. Paw withdrawal threshold (PWT) to mechanical stimulation and paw withdrawal latency (PWL) to a thermal nociceptive stimulus were measured on 0, 1, 3, 5, 7, 9, 11, 14 days during the consecutive 14 days of administration. The animals were sacrificed after the final IT administration. The lumbar segment of the spinal cord was removed for determination of the number of synapsis in the spinal dorsal horn by immuno-histochemistry in 4 animals in each group and observation of synaptic structure remodeling using electron microscope in another 4 animals in each group. Results Compared with group S, PWT was significantly decreased and PWL was shortened in the other 5 groups, and the number of synapsis was significantly increased and the synaptic structure was thickened in NP, NS, M and K groups (P ＜ 0.05). Compared with group NP,PWT was significantly increased and PWL was prolonged in M, K and MK groups, and the number of synapsis was significantly decreased and the thickness of synaptic structure was significantly reduced in group MK ( P ＜ 0.05).Compared with group M, PWT was significantly increased, PWL was prolonged, the number of synapsis was significantly decreased and the thickness of synaptic structure was significantly reduced in group MK ( P ＜ 0.05). Conclusion IT ketamine can inhibit the synaptic remodeling in the spinal dorsal horn during development of morphine tolerance in a rat model of NP.