Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain
Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain
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DOI：
10.1016/j.pain.2008.12.006
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发表时间：
2009-02-01
期刊：
影响因子：
7.4
通讯作者：
Przewlocki, Ryszard
中科院分区：
文献类型：
--
作者：
Obara, Ilona;Parkitna, Jan Rodriguez;Przewlocki, Ryszard
我们研究了局部足底内(i.pl.)注射多肽和非肽类阿片受体激动剂在大鼠炎性和神经病理性疼痛模型中的作用。局部应用激动剂可剂量依赖地减少福尔马林引起的炎症爪子退缩，并在坐骨神经结扎诱导的神经病理性疼痛中诱导抗痛敏和抗过敏效应。选择性阿片受体拮抗剂和非选择性阿片受体拮抗剂均证实，这些作用是通过位于组织/神经损伤侧的外周阿片受体介导的。在神经病和炎症中诱导镇痛所需的µ和kappa激动剂的ED50剂量范围远高于炎症的ED50；此外，在两种疼痛模型中，只有增量激动剂在相同的剂量范围内有效。此外，与非肽类阿片相比，有效的抗痛觉作用是在较低剂量的多肽中实现的。这些发现支持外周给药阿片肽，特别是增量激动剂，用于治疗慢性疼痛。此外，为了评估阿片基因表达的适应性是否可以作为神经病理性疼痛阿片类药物疗效降低的临床观察的基础，我们分析了神经病变和炎症过程中脊髓和背根节(DRG)中阿片类药物转录物的丰度。神经损伤小丑调节DRG中所有类型阿片受体的mRNA，据预测阿片受体的合成减少可能是局部应用阿片类药物治疗神经疾病效果降低的原因。所获得的结果区分了炎症性疼痛和神经病理性疼痛，并为阿片类药物在这两种类型疼痛中的外周有效性提供了新的见解。(C)2008年国际疼痛研究协会。爱思唯尔出版，版权所有。
We investigated the efficacy of local intraplantar (i.pl.) injection of peptide and non-peptide mu-, delta- and kappa-opioid receptor agonists in rat models of inflammatory and neuropathic pain. Locally applied agonists dose-dependently reduced formalin-induced flinching of the inflamed paw and induced antiallodynic and antihyperalgesic effects in sciatic nerve ligation-induced neuropathic pain. These effects were mediated by peripheral opioid receptors localized at the side of tissue/nerve injury, as was demonstrated by selective and non-selective opioid receptors antagonists. The ED50 dose range of mu- and kappa-agonists required to induce analgesia in neuropathy was much higher than the ED50 for inflammation; moreover, only delta-agonists were effective in the same dose range in both pain models. Additionally, effective antin-ociception was achieved at a lower dose of peptide, compared to non-peptide, opioids. Such findings support the use of the peripheral administration of opioid peptides, especially delta-agonists, in treating chronic pain. Furthermore, in order to assess whether adaptations in the expression of opioid genes could underlie the clinical observation of reduced opioid effectiveness in neuropathic pain, we analyzed the abundance of opioid transcripts in the spinal cord and dorsal root ganglia (DRG) during the neuropathy and inflammation. Nerve injury clown-regulated mRNA for all types of opioid receptors in the DRG, which is predicted to decrease in the synthesis of opioid receptors to possibly account for the reduced effectiveness of locally administered opioids in neuropathy. The obtained results differentiate inflammatory and neuropathic pain and provide a novel insight into the peripheral effectiveness of opioids in both types of pain. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.