早期系统性给予IL-10对成年大鼠胫神经损伤后神经病理性疼痛的抑制作用  

Early Systemic Administration of IL-10 Inhibits Neuropathic Pain in Adult Rats with Tibial Nerve Injury

作　　者：冯亚平[1,2] 丁有权 任弘毅[1] 李轩漾[1] 覃扬[2] 齐建国[1] 

机构地区：[1]四川大学华西基础医学与法医学院组织胚胎学与神经生物学教研室,成都610041 [2]四川大学华西基础医学与法医学院生物化学与分子生物学教研室,成都610041

出　　处：《四川大学学报（医学版）》2016年第5期636-641,664,共7页Journal of Sichuan University(Medical Sciences)

基　　金：四川省科技厅科技支撑计划项目(No.2013SZ0069)资助

摘　　要：目的 探究早期系统性给予白介素-10（IL-10）对成年大鼠胫神经损伤后周围性神经病理性疼痛的影响。方法 成年雄性SD大鼠随机分为假手术组、胫神经永久性横断伤（即改良型备用性神经损伤,modified spared nerve injury,mSNI）组、IL-10给药的mSNI组和磷酸缓冲盐溶液（PBS）给药的mSNI组,每组各6只。根据各组的设定进行右侧胫神经永久横断或相应假手术,并在术后立即一次性腹腔注射50μg IL-10（0.1mg/mL）或等体积PBS。每组动物分别于术前（0d）及术后4/5d、7/8d、14/15d在后肢足底隐神经和腓肠神经支配皮肤区域进行足底实验、丙酮测试、von Frey hairs测试、针刺实验以检测其疼痛反应。此外,随机选取6只SD大鼠建立坐骨神经分支选择损伤（spared nerve injury,SNI）模型（胫神经和腓总神经联合横断）,并在术后8d观察其后肢足跖外翻状态与mSNI组的异同。结果 mSNI组大鼠损伤同侧后肢足跖外翻状态较SNI组明显减轻。在足底实验、丙酮测试、von Frey hairs测试、针刺实验4种测试中,mSNI组大鼠损伤同侧足底的隐神经和腓肠神经支配皮肤区域在术后4/5d均出现明显的病理性疼痛反应,并持续到术后14/15d。而其损伤对侧及假手术动物损伤同侧及对侧均无明显的病理性疼痛反应。IL-10给药的mSNI组大鼠在损伤同侧足底的隐神经和腓肠神经支配皮肤区域的各种病理性疼痛行为反应在术后4~7d均得到明显的缓解,并持续到术后15d,而PBS给药的mSNI组损伤同侧仍持续保持明显的神经病理性疼痛反应。结论 成年大鼠胫神经永久性横断是一种有效的周围性神经病理性疼痛模型,早期系统性注射的给药方式可有效发挥IL-10对周围性神经病理性疼痛的抑制作用。Objective To determine the effect of early systemic administration of IL-10 on peripheral neuropathic pain induced by tibial nerve permanent transection [modified spared nerve injury （mSNI）] in adult rats. Methods Male adult Sprague-Dawley （SD） rats （ten-week old, 250-300 g） with mSNI were randomly divided into mSNI, sham-operated, IL-10 intervention （intraperitoneal injection）, PBS intervention （intraperitoneal injection） groups, each containing six rats. Intraperitoneally injections （IL-10 or PBS） were given immediately after surgeries for a single regime with a dosage of 500μL （0. 1 mg/mL）. Plantar test, yon Frey hairs test, pinprick test and acetone test were performed before and after tibial nerve injuries （0 d, 4/5 d, 7/8 d, 14/15 d） to evaluate region- specific pain responses of the rats on the plantar sural and saphenous skin territories of ipsilateral and contralateral hindpaws. The hindpaw position （on 8 d） of six additional rats with standard SNI was compared with those with mSNI. Results The rats with standard SNI showed an eversion posture of hindpaws, more prominent than those with mSNI. Region-specific pathological pain evoked by mechanical and thermal stimuli on the sural and saphenous skin territories of the plantar surfaces of rat hindpaws was demonstrated on the ipsilateral rather than contralateral hindpaws. This effect was shown in the rats with mSNI but not in those with sham operations. Compared with PBS, early intraperitoneal injection of IL-10 significantly and persistently attenuated either allodynia or hyperalgesia in the rats with mSNI. Conclusion Tib but useful rodent model of peripheral pathogenesis of neuropathic pain induced ial nerve permanent transection models of adult rats can be used as a simple neuropathic pain. Early systemic administration of IL-IO impairs the by tibial nerve injuries.

关 键 词：胫神经永久性横断 神经病理性疼痛 白介素-10 

分 类 号：R741[医药卫生—神经病学与精神病学]