胫骨骨癌痛模型大鼠鞘内注射舒芬太尼后脊髓背角N-甲基-D-天冬氨酸受体及降钙素基因相关肽的表达

Effects of intrathecal Sufentanil injection on the expression of N-methyl-D-aspartate receptor and calcitonin gene-related peptide in the spinal dorsal horn of rat bone cancer pain models

背景:临床和动物实验证实舒芬太尼鞘内注射有明显的镇痛效果,但其机制尚不明确。目的:观察鞘内注射舒芬太尼对骨癌痛大鼠痛阈及脊髓背角N-甲基-D-天冬氨酸受体、降钙素基因相关肽表达的影响。方法:健康SD大鼠36只随机等分为对照组、假手术组、模型组和舒芬太尼组。后2组利用乳腺癌细胞腹水制备胫骨骨癌痛模型,假手术组注射加热灭活后的死细胞。模型组和舒芬太尼组在建模后15d内每天鞘内注射生理盐水和舒芬太尼。结果与结论:与对照组和假手术组比较,模型组大鼠在建模后第12和14天脊髓背角N-甲基-D-天冬氨酸受体和降钙素基因相关肽表达增加(P<0.01),且出现机械性异常疼痛痛阈降低,热刺激后爪退缩潜伏时间缩短(P<0.01);而与模型组比较,舒芬太尼组大鼠,在注药后第12和14天脊髓背角浅层N-甲基-D-天冬氨酸受体和降钙素基因相关肽的表达降低(P<0.01),且机械刺激痛阈提高以及热刺激后爪潜伏期延长(P<0.01)。提示鞘内注射舒芬太尼对骨癌痛大鼠具有明显的抗伤害效应,其机制与抑制大鼠脊髓背角N-甲基-D-天冬氨酸受体和降钙素基因相关肽表达有关。

BACKGROUND： There are considerable animal experiments and clinical evidence indicating obvious analgesic effects of intrathecal Sufentanil injection, but the mechanism behind this is unclear. OBJECTIVE： To investigate the effects of intrathecal Sufentanil injection on the expression of N-methyI-D-aspartate recaptors and calcitonin gene-related peptide in spinal dorsal horn of rat bone cancer pain models. METHODS： A total of 36 healthy male Sprague Dawley rats were randomly divided into four groups： control group, sham operation group, bone cancer pain model group and Sufentanil group. Bone cancer pain model in the latter two groups was constructed using ascitic fluid of breast cancer cells. Rats in sham operation group were injected with heat inactivated dead cells. Rats in model group and Sufentanil group were treated with saline and Sufentanil daily by intrathecal injection within 15 days after model construction. RESULTS AND CONCLUSION： Compared with control group and sham operation group, the expression of N-methyI-D-aspartate recaptors and calcitonin gene-related peptide in spinal dorsal horn increased in model group on the 12th and 14th days after model construction （P 〈 0.01 ）. The mechanical allodynia pain threshold and radiant heat stimulus paw withdrawal latency decreased in model group （P 〈 0.01 ）. Compared with model group, the expression of N-methyI-D-aspartate recaptors and calcitonin gene-related peptide in the superficial layer of spinal dorsal horn decreased on the 12th and 14th days after injection （P 〈 0.01 ）. The mechanical allodynia pain threshold and radiant heat stimulus paw withdrawal latency increased （P 〈 0.01 ）. It suggests that intrathecal administration of Sufentanil provide a significant antinociception effect in rat bone cancer pain models, and the mechanisms behind this is related to the inhibition of N-methyI-D-aspartate recaptors and calcitonin gene-related peptide in rat spinal dorsal horn.