Kalmar B, Greensmith L, Malcangio M, McMahon S B, Csermely P, Burnstock G
Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London WC1N 3BG, UK.
Exp Neurol. 2003 Dec;184(2):636-47. doi: 10.1016/S0014-4886(03)00343-1.
In this study, we examined the effect BRX-220, a co-inducer of heat shock proteins, in injury-induced peripheral neuropathy. Following sciatic nerve injury in adult rats and treatment with BRX-220, the following features of the sensory system were studied: (a) expression of calcitonin gene-related peptide (CGRP); (b) binding of isolectin B4 (IB4) in dorsal root ganglia (DRG) and spinal cord; (c) stimulation-evoked release of substance P (SP) in an in vitro spinal cord preparation and (d) nociceptive responses of partially denervated rats. BRX-220 partially reverses axotomy-induced changes in the sensory system. In vehicle-treated rats there is a decrease in IB4 binding and CGRP expression in injured neurones, while in BRX-220-treated rats these markers were better preserved. Thus, 7.0 +/- 0.6% of injured DRG neurones bound IB4 in vehicle-treated rats compared to 14.4 +/- 0.9% in BRX-220-treated animals. Similarly, 4.5 +/- 0.5% of DRG neurones expressed CGRP in the vehicle-treated group, whereas 9.0 +/- 0.3% were positive in the BRX-220-treated group. BRX-220 also partially restored SP release from spinal cord sections to electrical stimulation of primary sensory neurones. Behavioural tests carried out on partially denervated animals showed that BRX-220 treatment did not prevent the emergence of mechanical or thermal hyperalgesia. However, oral treatment for 4 weeks lead to reduced pain-related behaviour suggesting either slowly developing analgesic actions or enhancement of recovery processes. Thus, the morphological improvement seen in sensory neurone markers was accompanied by restored functional activity. Therefore, treatment with BRX-220 promotes restoration of morphological and functional properties in the sensory system following peripheral nerve injury.
在本研究中，我们检测了热休克蛋白的共诱导剂BRX - 220在损伤诱导的周围神经病变中的作用。在成年大鼠坐骨神经损伤并给予BRX - 220治疗后，对感觉系统的以下特征进行了研究：（a）降钙素基因相关肽（CGRP）的表达；（b）背根神经节（DRG）和脊髓中异凝集素B4（IB4）的结合；（c）体外脊髓制备中电刺激诱发的P物质（SP）释放；以及（d）部分去神经大鼠的伤害性反应。BRX - 220部分逆转了轴突切断术引起的感觉系统变化。在给予赋形剂处理的大鼠中，损伤神经元的IB4结合和CGRP表达减少，而在给予BRX - 220处理的大鼠中，这些标志物得到了更好的保留。因此，在给予赋形剂处理的大鼠中，7.0±0.6%的损伤DRG神经元结合IB4，而在给予BRX - 220处理的动物中这一比例为14.4±0.9%。同样，在给予赋形剂处理的组中，4.5±0.5%的DRG神经元表达CGRP，而在给予BRX - 220处理的组中，9.0±0.3%为阳性。BRX - 220还部分恢复了脊髓切片对初级感觉神经元电刺激的SP释放。对部分去神经动物进行的行为测试表明，BRX - 220治疗并不能预防机械性或热性痛觉过敏的出现。然而，口服治疗4周导致疼痛相关行为减少，这表明可能存在缓慢发展的镇痛作用或恢复过程的增强。因此，感觉神经元标志物的形态学改善伴随着功能活性的恢复。所以，BRX - 220治疗促进了周围神经损伤后感觉系统形态和功能特性的恢复。
