BRAIN-DERIVED NEUROTROPHIC FACTOR, ACTING AT THE SPINAL CORD LEVEL, PARTICIPATES IN BLADDER HYPERACTIVITY AND REFERRED PAIN DURING CHRONIC BLADDER INFLAMMATION
BRAIN-DERIVED NEUROTROPHIC FACTOR, ACTING AT THE SPINAL CORD LEVEL, PARTICIPATES IN BLADDER HYPERACTIVITY AND REFERRED PAIN DURING CHRONIC BLADDER INFLAMMATION
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DOI：
10.1016/j.neuroscience.2012.12.044
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发表时间：
2013-03-27
期刊：
影响因子：
3.3
通讯作者：
Cruz, C. D.
中科院分区：
文献类型：
--
作者：
Frias, B.;Allen, S.;Cruz, C. D.
脑源性神经营养因子（BDNF）是一种参与慢性躯体疼痛的神经营养因子（NT）。最近的一项研究表明，BDNF可能在外周水平参与慢性膀胱炎。然而，这种NT的主要作用部位是中枢神经系统，最明显的是脊髓。中枢作用的BDNF对正常动物膀胱功能的影响及其在慢性膀胱炎中的中枢作用目前尚不清楚。本研究就是为了澄清这一问题。为此目的，对照非发炎动物鞘内注射BDNF，之后评估膀胱功能。这种治疗引起了短暂的膀胱过度活动，而慢性鞘内注射BDNF并没有引起这种效果。通过机械性异常性疼痛作为脑源性神经营养因子作用的内部对照来评估皮肤敏感性。为了确定BDNF在膀胱炎症中的作用，环磷酰胺诱导的膀胱炎动物接受了一般Trk受体拮抗剂或BDNF清除剂的鞘内注射。阻断Irk受体或BDNF隔离显着改善膀胱功能。此外，这些治疗还减少了通常在慢性膀胱炎大鼠中观察到的牵涉性疼痛。牵涉痛的减少伴随着脊髓细胞外信号调节激酶（ERK）磷酸化水平的降低，这是腰骶脊髓感觉障碍增加的标志物，以及脊髓BDNF表达。结果表明，BDNF，在脊髓水平上发挥作用，有助于膀胱过度活动和牵涉性疼痛，慢性膀胱炎的重要标志。此外，这些数据还支持开发BDNF调节剂作为治疗慢性膀胱炎症的假定治疗选择。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Brain-derived neurotrophic factor (BDNF) is a neurotrophin (NT) known to participate in chronic somatic pain. A recent study has indicated that BDNF may participate in chronic cystitis at the peripheral level. However, the principal site of action for this NT is the central nervous system, most notably the spinal cord. The effects of centrally-acting BDNF on bladder function in normal animals and its central role during chronic cystitis are presently unknown. The present study was undertaken to clarify this issue. For that purpose, control non-inflamed animals were intrathecally injected with BDNF, after which bladder function was evaluated. This treatment caused short-lasting bladder hyperactivity; whereas chronic intrathecal administration of BDNF did not elicit this effect. Cutaneous sensitivity was assessed by mechanical allodynia as an internal control of BDNF action. To ascertain the role of BDNF in bladder inflammation, animals with cyclophosphamide-induced cystitis received intrathecal injections of either a general Trk receptor antagonist or a BDNF scavenger. Blockade of Irk receptors or BDNF sequestration notably improved bladder function. In addition, these treatments also reduced referred pain, typically observed in rats with chronic cystitis. Reduction of referred pain was accompanied by a decrease in the spinal levels of extracellular signal-regulated kinase (ERK) phosphorylation, a marker of increased sensory barrage in the lumbosacral spinal cord, and spinal BDNF expression. Results obtained here indicate that BDNF, acting at the spinal cord level, contributes to bladder hyperactivity and referred pain, important hallmarks of chronic cystitis. In addition, these data also support the development of BDNF modulators as putative therapeutic options for the treatment of chronic bladder inflammation. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.