Ishigooka Manabu, Zermann Dirk-Henrik, Doggweiler Ragi, Schmidt Richard A, Hashimoto Tohru, Nakada Teruhiro
Department of Urology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan Neurourology Unit, Division of Urology, Colorado University Health Sciences Center, Denver, CO, USA.
Pain. 2001 Jul;93(1):43-50. doi: 10.1016/S0304-3959(01)00288-3.
It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long-term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. Changes in NK1R immunoreactivity after chronic bladder irritation were investigated in order to evaluate the existence of hypersensitive states in the spinal cord after chronic bladder irritation. Experiments were performed on a total of 12 adult female Sprague-Dawley rats. In six animals, cyclophosphamide (CPA) was administered intraperitoneally for 2 weeks. Another six animals were given intraperitoneal saline injections and served as the control group. After these treatments, immunohistochemical staining for NK1Rs and substance P in rat lumbosacral spinal cord was performed. In CPA-treated animals, NK1R-positive areas and staining intensity within the dorsal spinal cord were significantly increased in the L5 to S2 spinal cord areas, especially in the L6 and S1 segments. In the L6 spinal segment, CPA-treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA-treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.
有研究表明，长期的躯体炎症后，脊髓背角神经元上的神经激肽1受体（NK1R）会有显著上调。这种上调似乎在慢性疼痛状态下的中枢敏化中起重要作用。然而，尚不清楚在慢性内脏（膀胱）炎症后是否也会观察到这种变化。为了评估慢性膀胱刺激后脊髓中过敏状态的存在，研究了慢性膀胱刺激后NK1R免疫反应性的变化。总共对12只成年雌性Sprague-Dawley大鼠进行了实验。其中6只动物腹腔注射环磷酰胺（CPA），持续2周。另外6只动物腹腔注射生理盐水作为对照组。这些处理后，对大鼠腰骶部脊髓进行NK1R和P物质的免疫组织化学染色。在CPA处理的动物中，L5至S2脊髓区域，尤其是L6和S1节段，脊髓背角内NK1R阳性区域和染色强度显著增加。在L6脊髓节段，CPA处理增强了内侧和外侧背角以及包括骶副交感核在内的外侧板层中的NK1R免疫染色，但程度较轻。在CPA处理的动物中，P物质染色强度在NK1R免疫反应性增加的相同区域增加。这一发现可能意味着慢性内脏炎症后脊髓中NK1R上调以及中枢敏化的发生。
