Increased Nerve Fiber Expression of Sensory Sodium Channels Nav1.7, Nav1.8, and Nav1.9 in Rhinitis

Increased Nerve Fiber Expression of Sensory Sodium Channels Nav1.7, Nav1.8, and Nav1.9 in Rhinitis
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DOI:
10.1097/mlg.0b013e3181625d5a
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发表时间:
2008-04-01
期刊:
影响因子:
2.6
通讯作者:
Anand, Praveen
Anand, Praveen
中科院分区:
医学2区
文献类型:
--
作者:
Keh, Siew M.;Facer, Paul;Anand, Praveen

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简介:电压门控钠通道Nav1.7、Nav1.8和Nav1.9参与神经动作电位,并被认为是神经元超敏反应的基础。因此,我们研究了它们在过敏性和非过敏性鼻炎中的水平。材料和方法:下鼻甲活检50例(n = 18对照,n = 20过敏性鼻炎,n = 12非过敏性鼻炎)进行了免疫组织学研究,使用抗体Nav1.7,Nav1.8,Nav1.9,结构神经标记(蛋白基因产物[PGP]9.5)、神经生长因子(NGF)、肥大细胞(c-kit)、巨噬细胞(CD 68)和T细胞(CD 3)。结果:过敏性鼻炎大鼠小脑下角肌钠通道阳性神经纤维数均明显增多,与正常对照组相比,过敏性鼻炎大鼠小脑下角肌钠通道阳性神经纤维数明显增多,与正常对照组相比,过敏性鼻炎大鼠小脑下角肌钠通道阳性神经纤维数明显增多,与正常对照组相比,过敏性鼻炎大鼠小脑下角肌钠通道阳性神经纤维数明显增多(Nav1.7,P =.0004; Nav1.8,P =.028; Nav1.9,P =.02)和非过敏性(Nav1.7,P =.006; Nav1.8,P =.019; Nav1.9,P =.0037)鼻炎。非变应性鼻炎的上皮下神经支配(PGP9.5,P = 0.01)和上皮神经生长因子免疫反应性(P = 0.03)显著增加,与我们以前在变应性鼻炎中的报道相当。炎性细胞标志物显着增加过敏性(肥大细胞,P = 0.06;巨噬细胞,P = 0.044; T细胞,P = 0.007),但不nonallergic rhinitis.Conclusion:感觉钠通道在过敏性鼻炎和nonallergic鼻炎的水平增加可能有助于过敏状态,无论活动性炎症的程度。这些钠通道的选择性阻断剂,局部给药,可能对鼻炎有治疗潜力。
Introduction: Voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 are involved in nerve action potentials and have been proposed to underlie neuronal hypersensitivity. We have therefore studied their levels in allergic and nonallergic rhinitis.Materials and Methods: Inferior turbinate biopsies from 50 patients (n = 18 controls, n = 20 allergic, and n = 12 nonallergic rhinitis) were studied by immunohistology using antibodies to Nav1.7, Nav1.8, and Nav1.9, the structural nerve marker (protein gene product [PGP]9.5), nerve growth factor (NGF), mast cells (c-kit), macrophages (CD68), and T cells (CD3). Sodium channel-positive nerve fibers were counted per millimeter length of subepithelium, and immunoreactivity for inflammatory cell markers PGP9.5 and NGF were image analyzed.Results: All three sodium channel-immunoreactive nerve fiber numbers were significantly increased in allergic (Nav1.7, P =.0004; Nav1.8, P =.028; Nav1.9, P =.02) and nonallergic (Nav1.7, P =.006; Nav1.8, P, =.019; Nav1.9, P =.0037) rhinitis. There was a significant increase of subepithelial innervation (PGP9.5, P =.01) and epithelial NGF immunoreactivity (P =.03) in nonallergic rhinitis, comparable with our previous report in allergic rhinitis. Inflammatory cell markers were significantly increased in allergic (mast cells, P =.06; macrophages, P =.044; T cells, P =.007) but not nonallergic rhinitis.Conclusion: The increased levels of sensory sodium channels in allergic and nonallergic rhinitis may contribute to the hypersensitive state, irrespective of the degree of active inflammation. Selective blockers of these sodium channels, administered topically, may have therapeutic potential in rhinitis.