Differential contribution of the two phases of the formalin test to the pattern of c-fos expression in the rat spinal cord: Studies with remifentanil and lidocaine
Differential contribution of the two phases of the formalin test to the pattern of c-fos expression in the rat spinal cord: Studies with remifentanil and lidocaine
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DOI：
10.1016/s0304-3959(96)03285-x
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发表时间：
1997-01-01
期刊：
影响因子：
7.4
通讯作者：
Basbaum, AI
中科院分区：
文献类型：
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作者：
Abbadie, C;Taylor, BK;Basbaum, AI
在大鼠后爪注射福尔马林产生两个阶段的伤害性行为。尽管人们普遍认为第一阶段是由伤害性初级传入纤维的直接化学激活引起的，但导致第二阶段的因素尚未确定。在本研究中，我们监测的c-fos蛋白的表达，以评估是否背角神经元的活动模式不同的结果，在两个阶段正在进行的传入活动。为了选择性地阻断第一或第二相，我们分别使用了一种有效的短效阿片激动剂瑞芬太尼和一种不穿过血脑屏障的利多卡因的季铵衍生物QX-314。我们还评估了使用瑞芬太尼和利多卡因或局部麻醉药布比卡因和季铵利多卡因的组合在两个阶段消除伤害性行为的效果。在所有组中，将福尔马林（5%，50 μ l）皮下注射到后爪的足底表面。为了评估福尔马林产生的伤害性行为，我们监测了退缩的次数。在第一时相注射瑞芬太尼可完全阻断福尔马林诱发的第一时相伤害性行为，对第二时相无影响。在间期注射利多卡因完全阻断第二相伤害性行为。正如预期的那样，当瑞芬太尼在第一阶段和利多卡因在第二阶段，所有福尔马林诱发的伤害性行为被阻断。在第1和第2阶段分别接受布比卡因和利多卡因注射的大鼠也是如此。在L4-L5节段的I-II层中，瑞芬太尼（26.5%）和利多卡因（27.3%）的Fos表达下降幅度相当;瑞芬太尼和利多卡因联合给药时下降幅度更大（50.5%），布比卡因和利多卡因联合给药时下降幅度更大（74.2%）。在V-VI层，瑞芬太尼本身使c-fos表达降低39.4%;单独使用利多卡因，降低58.4%。当同时注射瑞芬太尼和利多卡因或布比卡因和利多卡因时，我们没有观察到进一步的显著降低（分别为69.7%和74.6%）。我们的研究结果不仅提供了强有力的证据表明，在第二阶段的活动是必要的，以保持最大的表达c-fos在脊髓中，但也揭示了显着的区域差异，在两个阶段期间产生的活动的中央模式。这些结果也证实了我们以前的报告，c-Sos的表达并没有消除时，伤害性刺激的行为表现被完全封锁。
Injection of formalin in the rat hindpaw produces two phases of nociceptive behavior. Although it is generally agreed that the first phase results from direct chemical activation of nociceptive primary afferent fibers, the factors that contribute to the second phase are not established. In the present study, we monitored the expression of the c-fos protein to evaluate whether the pattern of activity of dorsal horn neurons differs as a result of ongoing afferent activity during the two phases. To selectively block the first or second phase, we respectively used remifentanil, a potent and short acting opiate agonist, and QX-314, a quaternary derivative of lidocaine, which does not cross the blood brain barrier. We also evaluated the effect of eliminating nociceptive behavior in both phases using both remifentanil and lidocaine or a combination of local anesthetics, bupivicaine and quaternary lidocaine. In all groups, formalin (5%, 50 mu l) was injected subcutaneously into the plantar surface of the hindpaw. To assess the nociceptive behavior produced by formalin, we monitored the number of flinches. Injection of remifentanil during the first phase completely blocked the first phase formalin-evoked nociceptive behavior, and had no effect on the second phase. Injection of lidocaine during the interphase completely blocked second phase nociceptive behavior. As expected, when remifentanil was administered during the first phase and lidocaine during the second phase, all formalin-evoked nociceptive behavior was blocked. The same was true for rats that received injections of bupivicaine and lidocaine during phases 1 and 2, respectively. In laminae I-II of the L4-L5 segment, the magnitude of the decrease in Fos expression was comparable for remifentanil (26.5%) and lidocaine (27.3%); the decrease was greater when both remifentanil and lidocaine were administered (50.5%), and even greater when bupivicaine and lidocaine were used (74.2%). In laminae V-VI, remifentanil, by itself, decreased c-fos expression by 39.4%; for lidocaine alone, the decrease was 58.4%. We did not observe further significant decreases when both remifentanil and lidocaine, or bupivacaine and lidocaine were injected (69.7% and 74.6%, respectively). Our results not only provide strong evidence that activity during the second phase is necessary for maintaining the maximal expression of c-fos in the spinal cord, but also reveal significant regional differences in the central patterns of activity generated during the two phases. These results also confirm our previous reports that c-Sos expression is not eliminated when the behavioral manifestation of the noxious stimulus is completely blocked.