Influences of aberrant ionic channel expression in primary afferent Aβ fibers on neuropathic pain

Kvl.1和Kv1.2是电压门控性钾(K+)通道中密切相关的成孔亚基，在外周神经系统中大量表达。为了阐明这些亚基在初级感觉传入中的生物学作用，我们使用特定的多克隆抗体进行了免疫组织化学分析。在免疫组织化学染色中，背根和三叉神经节显示Kvl.1和Kv1.2在初级感觉神经元的中、大胞体中有较强的免疫反应。双重免疫荧光实验显示，强免疫反应神经元以RT97(神经细丝)阳性最多，但外周蛋白或IB4阳性较少。在棘突背角，抗Kvl.1和抗Kv1.2抗体均对较深的板层III-IV染色较深。这些结果提示，由Kv1.1和/或Kv1.2亚基组成的电压门控通道可能在…的机械感觉和本体感觉传导中起重要作用更多的皮肤和肌肉。我们还观察到，当结扎坐骨神经时，DRG神经元的Kv1.2-IR减少。我们现在假设，周围神经损伤后，特定亚型K+通道的活性降低，导致初级感觉神经元的异常兴奋性，(手稿，正在准备中)在Parrell中，我们试图识别周围神经扰动后未调控的蛋白质。我们发现，坐骨神经延长可诱导背根神经节神经元产生白介素6，雪旺细胞产生肿瘤坏死因子-α(Tumor NectorFor-α，α)。这种诱导不仅在急性延长的20 mm/d组中可见，而且在逐渐延长的1 mm/d和2 mm/d组中也可检测到，在这些组中未检测到变性改变。这些数据表明，IL-6和肿瘤坏死因子-α的表达水平在周围神经系统中受到微妙的调节。(Osamura等人，Exp.神经。191：61-70,2005；Hagiwara等人，J.Orthop。未来，我们将研究IL-6和肿瘤坏死因子-α在神经病理性疼痛模型中是否改变Kvl.1和Kv1.2蛋白的表达水平。较少

Kvl.1 and Kv1.2 are closely related pore-forming subunits of voltage-gated potassium (K+) channels, and are abundantly expressed in the peripheral nervous system. To clarify biological roles of these subunits in primary sensory afferentiation, we performed immunohistochemical analysis using specific polyclonal antidodies. In immunopeoxidase staining, dorsal root and trigeminal ganglia revealed that intense immunoreactivity (IR) for Kvl.1 and Kv1.2 was prediominant in medium to large cell bodies of primary sensory neurons. Double-immunofluorescence experiments revealed that the strongly immunoreactive neurons were most frequently RT97 (neurofilament)-positive; but rarely peripherin-or IB4-positive. In the spinad dorsal horn, both the anti-Kvl.1 and anti-Kv1.2 antibodies heavily stained the deeper laminae III-IV. These results suggest that voltage-gated channels composed of Kvl.1 and/or Kv1.2 subunits may play important roles in conducting mechanoceptive and proprioceptive sensation from … More skin and muscles. We also observed that, when sciatic nerve was ligated, Kv1.2-IR was reduced in DRG neurons. We now hypothesize that activities of particular subtypes of K+ channels are reduced after peripheral nerve injury, resulting in abnormal excitability of primary sensory neurons, (manuscript, in preparation) In pararell, we attempted to identify proteins unregulated after peripheral nerve perturbation. We demonstrated that sciatic nerve elongation induces production of interleukin-6 (IL-6) in DRG neurons and tumor necrosis factor-alpha (TNF-α) in Schwann cells. The induction was detected not only in the acutely elongated 20-mm/d group, in which nuclear eccentricity in the cell body and degenerated axons were observed, but also in the gradually elongated 1-and 2-mm/d groups, in which no degenerative change was detectable. These data indicate that the expression levels of IL-6 and TNF-α are regulated delicately in the peripheral nervous system. (Osamura, et al., Exp. Neurol. 191: 61-70, 2005; Hagiwara et al., J. Orthop. Sci.10: 614-621, 2005) In the future, we will examine whether or not IL-6 and TNF-α alter expression levels of Kvl.1 and Kv1.2 proteins in neuropathic pain models. Less