JNK抑制剂对福尔马林内脏炎症痛大鼠痛觉敏感化的影响

摘要

目的:考察JNK抑制剂SP600125对大鼠内脏炎症痛疼痛评分和脊髓背角神经元电活动的影响,探索JNK抑制剂对内脏炎症痛痛觉敏感化的作用.方法:清洁级雄性SD大鼠,重200～250 g,随机分为4组:福尔马林直肠致炎组(F组);福尔马林直肠致炎和脊髓蛛网膜下腔内插管组(IT组);福尔马林直肠致炎、脊髓蛛网膜下腔内插管并注射生理盐水组(NaCl组);福尔马林直肠致炎、脊髓蛛网膜下腔内插管并注射SP600125组(SP600125组);每组大鼠12只,共48只.4组大鼠,每组8只,每15 min作为一个时间段,共8个时间段,分别记录内脏炎症痛疼痛评分和脊髓背角神经元放电.结果:四组大鼠都在注射福尔马林后30 min均达到疼痛评分的最大值,并且在福尔马林注射后45 min至120 min之间,其疼痛评分逐渐降低至正常.SP600125组在前90 min内疼痛分数显著低于F组(P<0.05或P<0.01),而IT组和NaCl组与F组相比未见显著性差异.注射福尔马林后,F组神经元放电频率均立即明显增加,致炎后0～15 min、15～30 min和30～45 min内的放电频率分别为致炎前基线水平的252.36±28.76％、288.74±40.64％和186.47±32.16％,与致炎前相比均有显著性增加(P<0.05或P<0.01).SP600125组在致炎后0～15 min、15～30 min和30～45 min两时间段的脊髓背角神经元放电频率分别为基线水平的146.86％±25.79％、175.49％±28.74％和126.48％±21.68％,分别与F组致炎后0～15 min、15～30 min和30～45 min内的放电频率(252.36±28.76％、288.74±40.64％和186.47±32.16％)相比均有显著性的降低(P<0.05或P<0.01);F和IT、NaCl组相比没有显著性差异.结论:JNK抑制剂SP600125通过降低内脏炎症痛疼痛评分和抑制脊髓背角神经元放电,起到抑制内脏炎症痛痛觉敏感化作用,JNK可能为内脏炎症痛镇痛靶点之一.%Objective:To investigate the effect of JNK inhibitor (SP600125) on pain sensitization of visceral inflammatory pain in rats.Methods: Fourty-eight male SD rats (clean grade, weighing 200-250 g) were ran-domly divided into four groups (12 rats each group): formalin-induced rectal inflammation group (group F), formalin-induced rectal inflammation and spinal subarachnoid intubation group (group IT), formalin-induced rectal inflammation and spinal subarachnoid intubation with the injection of normal saline (group NaC1), for-malin-induced rectal inflammation and spinal subarachnoid intubation with the injection of SP 600125 (groupSP600125). The score of visceral inflammatory pain (SVIP) and discharge of spinal cord dorsal horn neurons were recorded eight times every 15 min.Results:In all of the four groups, the SVIP reached their peak at 30 min after the formalin injection and the SVIP decreased gradually to normal levels from 45 min to 120 min after the injection. In group SP600123, the SVIP was significantly lower than that of group F in 0-90 min (P< 0.05 orP< 0.01). There was no significant difference among groups F, IT and NaC1. In Group F, the discharge frequency of neurons increased immediately after the injection of formalin and they were 252.36±28.76％, 288.74±40.64％ and 186.47±32.16％ of the baseline level during the periods of 0-15 min, 15-30 min and 30-45 min, respectively. In the same periods, the discharge frequencies of the spinal dorsal horn neurons in group SP600125 were 146.86％±25.79％, 175.49％±28.74％ and 126.48％±21.68％ of the baseline level. Compared with group F, the discharge frequency decreased significantly in SP600125 group at these periods (P< 0.05 orP< 0.01). There was no significant difference among groups F, IT and NaCl (P> 0.05). Conclusion:The JNK inhibitor SP600125 reduces the SVIP and the spinal dorsal horn neuron discharges, suggesting that SP600125 can inhibit the pain sensitization of visceral inflammatory pain. JNK may be a potential target for the treatment of visceral inflammatory pain.