Dual effects of intrathecal BAM22 on nociceptive responses in acute and persistent pain-potential function of a novel receptor
Dual effects of intrathecal BAM22 on nociceptive responses in acute and persistent pain-potential function of a novel receptor
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DOI：
10.1038/sj.bjp.0705637
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发表时间：
2004-02-01
影响因子：
7.3
通讯作者：
Zeng, XA
中科院分区：
文献类型：
--
作者：
Hong, YG;Dai, PF;Zeng, XA
1牛肾上腺髓质22肽(BAM22)是脑啡肽原A的一种切割产物，它与阿片受体和新发现的受体在体外都有很高的亲和力。后者最初被命名为感觉神经元特异性受体，在此被称为具有非阿片活性的BAM多肽激活受体(BPAR)。BPAR在小直径背根节神经元中有独特的分布，其中大部分与1134类伤害性感受器传入有关。2本研究观察了鞘内注射BAM22对福尔马林诱导的大鼠伤害行为和尾部戒断潜伏期的影响。3鞘内(I.T.)在福尔马林试验的第一和第二阶段，服用BAM22降低了敌意行为得分，以退缩和举起/舔的总和来衡量。这种下降可通过全身注射纳洛酮来部分缓解。BAM22对福尔马林试验中观察到的致病行为具有剂量依赖性的抑制作用。BAM22(5nmolBAM22)在纳洛酮存在和不存在的情况下，在第二阶段的缩腿效应和举起/舔效应的比率分别为0.65和0.74。5 BAM22剂量为5nmol时，在没有和存在纳洛酮的情况下，尾部撤退潜伏期分别增加了基线的193和119%。6在福尔马林测试的第二阶段，单独全身注射纳洛酮增强了小鼠的新行为，但在第一阶段没有增加。纳洛酮治疗没有改变尾部戒断潜伏期。7这些数据证实了早些时候的体外数据，表明BAM22既有阿片类生物作用，也有非阿片类生物作用。BAM22的非阿片类作用包括在脊髓水平抑制急性和持续的伤害性行为，这可能是通过BPAR介导的。8讨论了这种新受体的名称、潜在的生理功能及其配体。
1 Bovine adrenal medulla 22 (BAM22) peptide is one of the cleavage products of proenkephalin A. It binds with high affinity to both opioid receptors and a newly discovered receptor in vitro. This latter receptor was first named sensory neuron-specific receptor and is here named BAM peptide-activated receptor with non-opioid activity (BPAR). BPAR is uniquely distributed in small-diameter DRG neurons, most of which are associated with the 1134 class of nociceptor afferent.2 The present study examined the effects of intrathecal administration of BAM22 on formalin-induced nocifensive behaviors and tail-withdrawal latency in the rat.3 Intrathecal (i.t.) administration of BAM22 decreased nocifensive behavior scores, measured as the sum of flinching and lifting/licking, in the first and second phases of the formalin test. This decrease was partially attenuated by systemic injection of naloxone.4 In the presence of naloxone, i.t. BAM22 produced a dose-dependent suppression of the nocifensive behaviors observed during the formalin test. The ratio of the efficacy of BAM22 (5 nmol) in the presence of naloxone over that in the absence of naloxone was 0.65 for flinching and 0.74 for lifting/licking in the second phase.5 BAM22 at a dose of 5 nmol increased the tail-withdrawal latency by 193 and 119% of baseline in the absence and presence of naloxone, respectively.6 Systemic administration of naloxone alone enhanced the nocifensive behaviors in the second, but not in the first phase of the formalin test. Naloxone treatment did not alter the tail-withdrawal latency.7 These data confirm earlier in vitro data showing that BAM22 has both opioid and non-opioid biological actions. The non-opioid action of BAM22 involves inhibition of acute and persistent nociceptive behaviors at the spinal level, presumably mediated via BPAR.8 The name suggested for this novel receptor, its potential physiological function and its ligand are discussed.