Plasma Membrane Mechanisms in a Preclinical Rat Model of Chronic Pain
Plasma Membrane Mechanisms in a Preclinical Rat Model of Chronic Pain
复制标题
DOI：
10.1016/j.jpain.2014.10.007
复制
发表时间：
2015-01-01
期刊：
影响因子：
4
通讯作者：
Levine, Jon D.
中科院分区：
文献类型：
--
作者：
Ferrari, Luiz F.;Levine, Jon D.
我们最近的研究表明，慢性疼痛的临床前模型中前列腺素E-2痛觉过敏的延长是由隔离素b4阳性伤害感受器释放环磷酸腺苷及其通过外核苷酶代谢产生腺苷介导的。反过来，腺苷在A1腺苷受体的自分泌机制中起作用，该受体在伤害感受器中的下游信号机制被改变以产生伤害感受器致敏。我们之前的研究表明，对细胞外基质分子versican的反义作用消除了前列腺素E-2痛觉过敏的延长，versican定义了痛觉引发的伤害感受器群体。为了进一步评估细胞外基质和痛觉感受器质膜之间的界面参与痛觉过敏延长的机制，我们用反义寡脱氧核苷酸打断了参与细胞质信号传导的质膜分子整合素β 1。整合素A1反义消除了由腺苷A1受体激动剂环戊腺苷引起的机械痛觉过敏。我们还用甲基- β -环糊精破坏了一个包含整合素β 1、脂筏的信号分子复合物，它在不影响前列腺素E-2痛觉过敏的急性期的情况下减少了延长，而对环戊腺苷痛觉过敏没有影响。我们的发现有助于确定慢性疼痛临床前模型中涉及的质膜机制。观点：目前的研究有助于进一步了解参与从急性到慢性疼痛转变的质膜信使组织的机制。(C) 2015年由美国疼痛协会发布
We have recently shown that the prolongation of prostaglandin E-2 hyperalgesia in a preclinical model of chronic pain-hyperalgesic priming-is mediated by release of cyclic adenosine monophosphate from isolectin B4-positive nociceptors and its metabolism by ectonucleotidases to produce adenosine. The adenosine, in turn, acts in an autocrine mechanism at an A1 adenosine receptor whose downstream signaling mechanisms in the nociceptor are altered to produce nociceptor sensitization. We previously showed that antisense against an extracellular matrix molecule, versican, which defines the population of nociceptors involved in hyperalgesic priming, eliminated the prolongation of prostaglandin E-2 hyperalgesia. To further evaluate the mechanisms at the interface between the extracellular matrix and the nociceptor's plasma membrane involved in hyperalgesia prolongation, we interrupted a plasma membrane molecule involved in versican signaling, integrin beta 1, with an antisense oligodeoxynucleotide. lntegrin A1 antisense eliminated mechanical hyperalgesia induced by an adenosine A1 receptor agonist, cyclopentyladenosine, in the primed rat. We also disrupted a molecular complex of signaling molecules that contains integrin beta 1, lipid rafts, with methyl-beta-cyclodextrin, which attenuated the prolongation without affecting the acute phase of prostaglandin E-2 hyperalgesia, while having no effect on cyclopentyladenosine hyperalgesia. Our findings help to define the plasma membrane mechanisms involved in a preclinical model of chronic pain. Perspective: The present study contributes to a further understanding of mechanisms involved in the organization of messengers at the plasma membrane that participate in the transition from acute to chronic pain. (C) 2015 by the American Pain Society