TRPV1 unlike TRPV2 is restricted to a subset of mechanically insensitive cutaneous Nociceptors responding to heat

TRPV1 unlike TRPV2 is restricted to a subset of mechanically insensitive cutaneous Nociceptors responding to heat
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DOI:
10.1016/j.jpain.2007.12.001
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发表时间:
2008-04-01
期刊:
影响因子:
4
通讯作者:
Koerber, H. Richard
Koerber, H. Richard
中科院分区:
医学2区
文献类型:
--
作者:
Lawson, Jeffrey J.;Mcllwrath, Sabrina L.;Koerber, H. Richard

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在本研究中,小鼠离体体感系统制备用于确定皮肤感觉神经元染色阳性TRPV 1或TRPV 2的反应特性。TRPV 1免疫染色仅在一组对感受野加热有反应的机械不敏感的无髓鞘(C)伤害感受器中发现(11/11)。对机械刺激和热刺激都有反应的皮肤C纤维对TRPV 1无阳性染色(0/62)。TRPV 2和热传导特性之间的关系并不清楚,因为很少有对热有反应的无髓鞘或有髓鞘纤维含有TRPV 2。TRPV 2最常在机械敏感的有髓纤维中发现,包括低阈值和高阈值机械感受器(伤害感受器)。虽然TRPV 2仅在6个有髓鞘多模态伤害感受器中的1个中发现,但在大多数(10/16)有髓鞘机械伤害感受器中发现。因此,尽管TRPV 1作为皮肤感觉神经元中的热敏通道的体内作用被明确定义,但TRPV 2在皮肤神经元中的作用仍然未知。这些结果还表明,TRPV 1可能是必不可少的热transluction在一个特定的子集的机械不敏感的皮肤伤害感受器;这一子集可能构成一个离散的热输入途径炎症引起的热痛。含有TRPV 1的小鼠皮肤伤害感受器的独特子集与机械不敏感的C-具有许多共同属性人类中被认为在病理性疼痛状态中起作用的纤维。因此,这些鼠纤维提供了一个临床相关的动物模型,为进一步研究这组皮肤伤害感受器。(c)2008年,美国疼痛协会。
In the present study, a murine ex vivo somatosensory system preparation was used to determine the response characteristics of cutaneous sensory neurons staining positively for TRPV1 or TRPV2. TRPV1 immunostaining was found exclusively (11/11) in a specific set of mechanically insensitive unmyelinated (C) nociceptors that responded to heating of their receptive fields. No cutaneous C-fibers that responded to both mechanical and heat stimuli stained positively for TRPV1 (0/62). The relationship between TRPV`2 and heat transcluction characteristics was not as clear, as few unmyelinated or myelinated fibers that responded to heat contained TRPV2. TRPV2 was found most frequently in mechanically sensitive myelinated fibers, including both low threshold and high threshold mechanoreceptors (nociceptors). Although TRPV2 was found in only 1 of 6 myelinated polymodal nociceptors, it was found in a majority (10/16) of myelinated mechanical nociceptors. Thus, whereas the in vivo role of TRPV1 as a heat-sensitive channel in cutaneous sensory neurons is clearly defined, the role of TRPV2 in cutaneous neurons remains unknown. These results also suggest that TRPV1 may be essential for heat transcluction in a specific subset of mechanically insensitive cutaneous nociceptors; and that this subset may constitute a discrete heat input pathway for inflammation-induced thermal pain.Perspective: The distinct subset of murine cutaneous nociceptors containing TRPV1 has many attributes in common with mechanically insensitive C-fibers in humans that are believed to play a role in pathological pain states. Therefore, these murine fibers provide a clinically relevant animal model for further study of this group of cutaneous nociceptors. (c) 2008 by the American Pain Society.