Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).
Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).
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DOI：
10.1371/journal.pbio.0060013
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发表时间：
2008-01
期刊：
影响因子：
9.8
通讯作者：
Lewin GR
中科院分区：
文献类型：
--
作者：
Park TJ;Lu Y;Jüttner R;Smith ES;Hu J;Brand A;Wetzel C;Milenkovic N;Erdmann B;Heppenstall PA;Laurito CE;Wilson SP;Lewin GR
在所有哺乳动物中，组织炎症导致疼痛和对热和机械刺激的行为敏感化，称为痛觉过敏。我们研究了非洲裸鼹鼠的疼痛机制，这是一种不寻常的啮齿动物物种，缺乏疼痛相关的神经肽（例如，P物质）。裸鼹鼠表现出一种独特的和显着的缺乏疼痛相关的行为，两个强有力的致痛剂，酸和辣椒素。此外，当暴露于炎症性损伤或已知的介质，裸鼹鼠不显示热痛觉过敏。相比之下，裸鼹鼠在福尔马林试验中确实表现出伤害反应行为，并且在炎症后表现出机械性痛觉过敏。利用电生理学，我们发现裸鼹鼠的初级传入伤害感受器对酸刺激不敏感，这与该动物缺乏酸诱导的行为相一致。在鸟类、两栖动物和鱼类中观察到感觉神经元的酸转导，这表明在裸鼹鼠的进化过程中，这种转导机制已被选择性地禁用。相反，伤害感受器对辣椒素反应强烈，我们还发现感觉神经元表达一种对辣椒素敏感的瞬时受体电位香草酸通道-1离子通道。然而，辣椒素敏感的感觉神经元在裸鼹鼠的激活不产生疼痛相关的行为。我们发现，辣椒素敏感的伤害感受器在裸鼹鼠，大鼠在功能上连接到表面背角神经元在小鼠。然而，同样的伤害感受器也在功能上与深背角神经元相连，这种连接在小鼠中很少见。裸鼹鼠的疼痛生物学在哺乳动物中是独特的，因此对这种不寻常物种的疼痛机制的研究可以为什么构成“正常”哺乳动物伤害感受提供重要的见解。辣椒素和辣椒酸等化学物质被认为是有毒的，因为它们在应用于皮肤时会引起刺激和疼痛。例如，酸是一种非常有害的刺激物，可以引起剧烈的疼痛。事实上，酸对所有动物都是有毒和痛苦的，包括两栖动物和鱼类。在这里，我们描述了一个成员的啮齿类动物家庭，非洲裸鼹鼠（Heterocephalus glaber），这是行为完全遗忘辣椒素和酸。组织损伤和炎症增加了对正常非疼痛刺激的敏感性，这种现象称为痛觉过敏。在这里，我们表明，裸鼹鼠不经历痛觉过敏疼痛的热刺激炎症后。据我们所知，迄今为止还没有其他哺乳动物被描述为对化学疼痛选择性不敏感或缺乏热痛觉过敏。裸鼹鼠生活在非常大的地下社会群体中，对低氧和高二氧化碳条件具有显著的耐受性。我们假设裸鼹鼠选择性疼痛不敏感，部分原因是选择压力所产生的极端正常栖息地。非洲裸鼹鼠是一种不寻常的哺乳动物，它是独一无二的，因为它不受痛苦的化学物质的影响，而这些化学物质在所有其他研究的物种中都会引起剧烈的疼痛。
In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes “normal” mammalian nociception. Chemicals such as capsaicin and acid are considered noxious because they cause irritation and pain when applied to the skin. Acid is, for example, a very noxious stimulus and can cause intense pain. Indeed, acid is both noxious and painful to all animals including amphibians and fish. Here we describe a member of the rodent family, the African naked mole-rat (Heterocephalus glaber), that is behaviorally completely oblivious to capsaicin and acid. Tissue injury and inflammation increase sensitivity to normally non painful stimuli, a phenomenon called hyperalgesia. Here we show that the naked mole-rat does not experience hyperalgesia to painful thermal stimuli after inflammation. To our knowledge, no other mammal has so far been described that is selectively insensitive to chemical pain or that lacks thermal hyperalgesia. Naked mole-rats live in very large subterranean social groups and are remarkably tolerant to low-oxygen and high–carbon dioxide conditions. We hypothesize that naked mole-rats are selectively pain insensitive partly because of selection pressure arising from the extremity of their normal habitat. Naked but far from vulnerable, the African naked mole-rat is an unusual mammal that is unique because it is impervious to painful chemicals that cause severe pain in all other species studied.
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影响因子：
2.5
作者：
Koltzenburg, M;Stucky, CL;Lewin, GR
通讯作者：
Lewin, GR
DOI：
10.1016/0742-8413(91)90279-3
发表时间：
1991-01-01
期刊：
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY
影响因子：
--
作者：
HAWKINS, NS;HEARN, J;EVANS, RH
通讯作者：
EVANS, RH
影响因子：
2.9
作者：
JENQ, CB;COGGESHALL, RE
通讯作者：
COGGESHALL, RE
影响因子：
64.8
作者：
Cao, YQ;Mantyh, PW;Basbaum, AI
通讯作者：
Basbaum, AI
影响因子：
7.4
作者：
Gilchrist, HD;Allard, BL;Simone, DA
通讯作者：
Simone, DA