Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord:: Potential antinociceptive targets

Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord:: Potential antinociceptive targets
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DOI:
10.1016/j.pain.2006.09.039
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发表时间:
2007-05-01
期刊:
影响因子:
7.4
通讯作者:
Rice, Frank L.
Rice, Frank L.
中科院分区:
医学1区
文献类型:
--
作者:
Cannon, Keri E.;Chazot, Paul L.;Rice, Frank L.

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组胺H-3受体(H(3)Rs)的激活可减轻炎症和伤害感受,但外周神经支配中H(3)Rs的存在从未得到证实。在这里,我们使用抗体来定位H3 R在胡须垫,毛和无毛后爪皮肤,背根神经节(DRG),和大鼠,野生型小鼠和H3 R敲除(H3 KO)小鼠的脊髓。虽然H3 Rs已被假设为C和交感神经纤维,H3 R样免疫反应性(H3 R-LI)只检测到假定动脉周围A δ纤维和A β纤维,终止于迈斯纳小体和毛囊周围的披针形末梢。H3 R阳性动脉周围纤维细口径和共表达降钙素基因相关肽(CGRP),P物质,酸敏感离子通道3,和200 kDa的神经丝蛋白(NF)的免疫反应性。在表皮角质形成细胞和默克尔细胞上也检测到H3 R-LI,但在默克尔末梢、C纤维、任何其他A δ纤维或交感神经纤维上未检测到H3 R-LI。在DRG中,H3 R-LI主要分布在共表达NF-LI和CGRP-LI的中大型神经元上。在背角,CGRP-阳性纤维和不H3 R-LI广泛分歧在第二层,许多前者形成了一个丛在第五层。低水平的H3 R-LI也存在于A β纤维穿透浅表和深层的er椎板。H3 R-LI在大鼠和野生型小鼠中的分布相似,但在H3 KO小鼠中分别在A δ纤维和A β纤维中被消除或强烈减少。最近发表的行为结果,目前的研究结果表明,动脉周围,肽能,H3 R-含有A δ纤维可能是高阈值的机械伤害性感受的来源。(c)2006年国际疼痛研究协会。Elsevier B. V.出版,保留所有权利。
Activation of histamine H-3 receptors (H(3)Rs) reduces inflammation and nociception, but the existence of H(3)Rs on peripheral innervation has never been demonstrated. Here we use antibodies to locate H3Rs in whisker pads, hairy and glabrous hind paw skin, dorsal root ganglia (DRGs), and spinal cords of rats, wild type mice, and H3R knockout (H3KO) mice. Although H3Rs have been hypothesized to be on C and sympathetic fibers, H3R-like immunoreactivity (H3R-LI) was only detected on presumptive periarterial A delta fibers and on A beta fibers that terminated in Meissner's corpuscles and as lanceolate endings around hair follicles. The H3R-positive periarterial fibers were thin-caliber and coexpressed immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, acid sensing ion channel 3, and 200 kDa neurofilament protein (NF). H3R-LI was also detected on epidermal keratinocytes and Merkel cells, but not on Merkel endings, C fibers, any other A delta fibers, or sympathetic fibers. In DRGs, H3R-LI was preponderantly on medium to large neurons coexpressing NF-LI and mostly CGRP-LI. In dorsal horn, CGRP-positive fibers with and without H3R-LI ramified extensively in lamina II; many of the former formed a plexus in lamina V. Low levels of H3R-LI were also present on A beta fibers penetrating superficial and into deep er laminae. The distribution of H3R-LI was similar in rats and wild type mice, but was eliminated or strongly reduced in A delta fibers and A beta fibers, respectively, in H3KO mice. Taken with recently published behavioral results, the present findings suggest that periarterial, peptidergic, H3R-containing A delta fibers may be sources of high threshold mechanical nociception. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.