Adrenergic stimulation mediates visceral hypersensitivity to colorectal distension following heterotypic chronic stress.
Adrenergic stimulation mediates visceral hypersensitivity to colorectal distension following heterotypic chronic stress.
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DOI：
10.1053/j.gastro.2009.09.054
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发表时间：
2010-01
期刊：
影响因子：
29.4
通讯作者：
Sarna SK
中科院分区：
文献类型：
--
作者：
Winston JH;Xu GY;Sarna SK
慢性应激会加重或导致肠易激综合征（IBS）患者的腹痛和痉挛等症状复发。我们研究了慢性应激是否通过增加结肠壁中神经生长因子（NGF）的表达来增加血浆去甲肾上腺素和结肠特异性背根神经节（DRG）神经元的敏感性。在雄性Wistar大鼠中诱导异型慢性应激（HeCS），并分析神经学和分子反应。分析组织的NGF表达。HeCS显着增加内脏运动反应的结直肠扩张;神经生长因子的表达增加结肠肌层和粘膜/粘膜下层。在结肠特异性胸腰段DRG神经元中，基强度降低，静息膜电位去极化，动作电位的电发生增加。在远端结肠腔施用树脂毒素，全身施用抗NGF抗体，或在胸腰段DRG中通过k252 A或反义寡核苷酸抑制NGF受体TrkA阻断慢性应激诱导的内脏对结直肠扩张的高敏感性。阻断α1/α2和β1/β2肾上腺素能受体可防止应激诱导的内脏高敏感性和增加结肠壁NGF的表达。HeCS在结肠壁中未诱导任何炎症反应。外周应激介质去甲肾上腺素通过增加结肠壁中NGF的表达诱导内脏对结肠直肠扩张的超敏反应，这在没有炎症反应的情况下使初级传入神经敏感。
Chronic stress exacerbates or causes relapse of symptoms such as abdominal pain and cramping in patients with irritable bowel syndrome (IBS). We investigated whether chronic stress increases plasma norepinephrine and sensitizes colon-specific dorsal root ganglion (DRG) neurons by increasing the expression of nerve growth factor (NGF) in the colon wall. Heterotypic chronic stress (HeCS) was induced in male Wistar rats and neurologic and molecular responses were analyzed. Tissues were analyzed for NGF expression. HeCS significantly increased the visceromoter response to colorectal distension; expression of NGF increased in colonic muscularis externa and mucosa/submucosa. Rheobase decreased, resting membrane potential was depolarized, and electrogenesis of action potentials increased in colon-specific thoracolumbar DRG neurons. Luminal administration of resiniferatoxin in distal colon, systemic administration of anti-NGF antibody, or inhibition of the NGF receptor TrkA by k252A or antisense oligonucleotides in thoracolumbar DRG blocked the chronic stress-induced visceral hypersensitivity to colorectal distension. Blockade of α1/α2- and β1/β2-adrenergic receptors prevented the stress-induced visceral hypersensitivity and increased expression of NGF in the colon wall. HeCS did not induce any inflammatory response in the colon wall. The peripheral stress mediator norepinephrine induces visceral hypersensitivity to colorectal distension in response to HeCS by increasing the expression of NGF in the colon wall, which sensitizes primary afferents in the absence of an inflammatory response.
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影响因子：
29.4
作者：
Brierley, SM;Jones, RCW;Blackshaw, LA
通讯作者：
Blackshaw, LA
影响因子：
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作者：
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LEVIMONTALCINI, R
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DOI：
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发表时间：
2005-07-01
影响因子：
4.5
作者：
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通讯作者：
Mayer, EA
DOI：
10.1152/ajpgi.90712.2008
发表时间：
2009-06-01
影响因子：
4.5
作者：
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通讯作者：
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