Zou Wang-yuan, Guo Qu-lian, Yang Yong, Wang E, He Zheng-hua
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhonghua Yi Xue Za Zhi. 2008 Jul 29;88(29):2064-8.
To investigate the antinociceptive effect of intrathecal (IT) injection of Herpes simplex virus type I (HSV-1) amplicon vector-mediated HPPE on chronic neuropathic pain.
45 Sprague-Dawley rats underwent chronic constriction. Injury (CCI) of unilateral sciatic nerve and then were randomly divided into 3 equal groups: CCI + normal saline group, undergoing insertion of microspinal catheter into the subarachnoid space at the lumber region and intrathecal delivery of NS, CCI + pHSVIRES-LacZ (SHPZ) group undergoing intrathecal delivery of and recombinant HSV-I amplicon vector pHSVIRES-HPPE-LacZ containing human pre-proenkephalin (HPPE) gene, and CCI + blank vector (SHZ) group receiving pHSV-HPPE-LacZ. Another 15 rats underwent sham operation to be used as control group. One week after IT administration 9 rats from each group were killed with their lumber segments of spinal cord removed to detect the expression of LacZ by X-gal staining, HPPE mRNA expression by RT-PCR, and L-enkephalin (L-EK) content by radioimmunoassay. Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal latency (PWTL) were measured before CCI (baseline) and 3 days after CCI and then once a week for 5 weeks after IT administration.
After IT administration of SHPZ expression of HPPE mRNA was detected in the spinal cord. One week after the IT injection the L-EK level of the SHPZ group was (748 +/- 185 ng/L), significantly higher than those of the Sham operation, NS, and SHZ groups [(452 +/- 89), (453 +/- 92), and (451 +/- 99) ng/L respectively, all P < 0.05]. The PWMT and PWTL levels of the SHPZ group were significantly increased since 1 week after the IT administration in comparison with the baseline values and those of the other 3 groups (all P < 0.05), and these effects peaked in the third week and then lasted to the fifth week. However, the threshold to mechanical and thermal stimuli was not affected by intrathecal delivery of vehicle or SHZ compared with the threshold before intrathecal delivery.
Intrathecal administration SHPZ can produce significant analgesic effects on chronic neuropathic pain in rats.
研究鞘内注射I型单纯疱疹病毒（HSV-1）扩增载体介导的人前脑啡肽原（HPPE）对慢性神经病理性疼痛的抗伤害感受作用。
45只Sprague-Dawley大鼠接受单侧坐骨神经慢性缩窄损伤（CCI），然后随机分为3组，每组15只：CCI+生理盐水组，将微脊髓导管插入腰段蛛网膜下腔并鞘内注射生理盐水；CCI+pHSVIRES-LacZ（SHPZ）组，鞘内注射含人前脑啡肽原（HPPE）基因的重组HSV-I扩增载体pHSVIRES-HPPE-LacZ；CCI+空白载体（SHZ）组，接受pHSV-HPPE-LacZ。另取15只大鼠行假手术作为对照组。鞘内给药1周后，每组处死9只大鼠，取出腰段脊髓，通过X-gal染色检测LacZ的表达，通过RT-PCR检测HPPE mRNA的表达，通过放射免疫测定法检测亮氨酸脑啡肽（L-EK）含量。在CCI前（基线）、CCI后3天以及鞘内给药后5周每周测量一次爪部机械缩足阈值（PMWT）和爪部热缩足潜伏期（PWTL）。
鞘内注射SHPZ后，在脊髓中检测到HPPE mRNA的表达。鞘内注射1周后，SHPZ组的L-EK水平为（748±185 ng/L），显著高于假手术组、生理盐水组和SHZ组[分别为（452±89）、（453±92）和（451±99）ng/L，P均<0.05]。与基线值及其他3组相比，SHPZ组的PWMT和PWTL水平自鞘内给药1周后显著升高（P均<0.05），这些效应在第3周达到峰值，然后持续到第5周。然而，与鞘内给药前的阈值相比，鞘内注射载体或SHZ对机械和热刺激的阈值没有影响。
鞘内注射SHPZ可对大鼠慢性神经病理性疼痛产生显著的镇痛作用。
