Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms.

Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms.
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DOI:
10.1038/srep34493
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发表时间:
2016-09-30
期刊:
影响因子:
4.6
通讯作者:
Gupta K
Gupta K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Y;Lei J;Gupta M;Peng F;Lam S;Jha R;Raduenz E;Beitz AJ;Gupta K

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没有药物作用的电针等综合方法在治疗疼痛方面越来越受到重视。了解电针诱导镇痛的机制将有益于镰状细胞病(SCD)等慢性疼痛疾病,患者可能终生需要阿片类镇痛药。小鼠模型对于发展对疼痛的机制理解具有指导意义,但实施电针所需的麻醉/约束可能会改变潜在的机制。为了克服这些限制,我们开发了一种对有意识、自由活动、不受约束的小鼠进行电针治疗的方法。使用这项技术,我们在 SCD 和癌症转基因小鼠模型以及完全弗氏佐剂引起的疼痛中证明了显着的镇痛效果。我们证明了对男女机械痛觉过敏、冷痛觉过敏和深部组织痛觉过敏的全面抗伤害作用。有趣的是,个别小鼠对电针的反应不同,分为高反应、中反应和无反应。从机制上讲,电针显着改善了镰状小鼠外周和中枢的炎症和伤害性介质,与抗伤害性反应相关。在电针治疗的中度反应者中使用次优剂量的吗啡产生了与高反应者相同的镇痛作用。对有意识的自由活动的小鼠进行电针治疗提供了一种有效的方法来发展基于机制的镇痛理解,而不受麻醉剂或约束的影响。
Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints.
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