鞘内注射瞬时受体电位香草酸受体通道1阻滞剂对宫颈扩张性内脏痛反应的影响

Effects of intrathecal transient receptor potential vanilloid 1 blocker on cervical distension induced visceral pain response

目的运用急性宫颈扩张(UCD)性内脏痛模型,观察鞘内注射瞬时受体电位香草酸受体通道1(TRPV1)阻滞剂(SB-366791)对宫颈扩张引起的内脏痛反应的影响,探索宫颈扩张性内脏痛的分子机制。方法选取30只成年雌性未孕SD大鼠,异氟醚吸入麻醉下建立UCD模型,即经下腹部正中切口暴露宫颈,以两枚金属钩分别穿过宫颈两侧,一侧固定,一侧悬挂不同质量砝码(0、25、50及75 g)实施宫颈扩张,持续1 h;另外选取12只成年雌性未孕SD大鼠,麻醉下留置鞘内导管,并于7 d后建立UCD模型,大鼠随机分为两组(n=6),1组鞘内注射TRPV1阻滞剂(SB-366791),另1组鞘内注射等容量生理盐水,然后实施75 g张力宫颈扩张持续1 h,持续记录宫颈扩张期间腹直肌肌电(EMG)、心率及呼吸频率的变化。UCD术毕30 min取脊髓T12~L2节段检测c-FOS阳性神经元和TRPV1表达变化。结果UCD引起扩张强度依赖性的EMG活动增强(P<0.05)和T12~L2脊髓节段深背角和中央管区域的c-FOS阳性神经元数量增加(P<0.05),并且T12~L2脊髓节段TRPV1表达也随UCD张力增加而增加(P<0.05);与鞘内注射生理盐水组相比,鞘内注射TRPV1阻滞剂(SB-366791)组在UCD后EMG活动减弱(P<0.05),脊髓背角c-FOS表达降低(P<0.05)。结论大鼠宫颈扩张引起腹直肌肌电活动增强、脊髓c-FOS及TRPV1表达增加;鞘内注射TRPV1阻滞剂(SB-366791)能有效抑制UCD导致的内脏性疼痛反应。

Objective With the aid of an acute visceral pain model of uterine cervical distension (UCD), the present study aimed to observe the effects of intrathecal administration of transient receptor potential vanilloid 1 (TRPV1) antagonist SB-366791 on UCD induced-visceral nociception as well as its involved molecular mechanisms. Methods A total of 30 Sprague-Dawley-derived adult virgin female rats were used. UCD model was established under isoflurane inhalation anesthesia. Briefly, a lower abdominal incision at midline was made to expose the uteral cervix, two metal rods were inserted through both sides of the cervix separately, one rod was fixed and the other one was connected to a pulley system with application of manual weighted traction (0, 25, 50, 75 or 100 g) for simulating 1 h of cervical distension. In addition, 12 Sprague-Dawley-derived adult virgin female rats were subjected to intrathecal catheter implantation, and UCD was established 7 days later. The rats were divided randomly into two groups;one group was administrated with intrathecal SB-366791 while the other was administrated with the same volume of saline as control. The 75 g distension force was then applied for an hour and the electromyographic (EMG) of musculus rectus abdominis, heart rate as well as respiratory frequency were measured continuously during the surgery. The spinal cord (T12-L2) was collected 30 minutes after UCD for the detection of changes of c-FOS and TRPV1 expression. Results UCD increased EMG activity (P<0.05) and c-FOS expression (P<0.05) in the deep dorsal horn region and central canal of the spinal cord (T12-L2) in a stimuli-dependent manner, the expression of TRPV1 in the T12-L2 spinal cord also increased in response to UCD stimulation (P<0.05). Compared with the saline group, intrathecal SB-366791 significantly decreased EMG activity (P<0.05) as well as spinal c-FOS (P<0.05) expression induced by UCD. Conclusions UCD in rats increases EMG activity of musculus rectus abdominis as well as spinal c-FOS and TRPV1 expression. Intrathecal administration of TRPV1 antagonist SB-366791 significantly decreases the visceral nociception induced by UCD.