Pharmacology of inflammatory pain: local alteration in receptors and mediators.
Pharmacology of inflammatory pain: local alteration in receptors and mediators.
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DOI：
10.1159/000268118
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Holzer-Petsche U
中科院分区：
文献类型：
--
作者：
Holzer P;Holzer-Petsche U
炎症通常与痛觉过敏有关。理想情况下，一旦炎症得到解决，这种变化应该会减弱，但情况并不一定如此，因为组织中的表型变化可以持续存在，就像感染后肠易激综合征的情况一样。基本上，所有供应肠道的初级传入神经元都能对促炎介质敏感，因此启动和维持超敏反应的机制具有重要的治疗意义。有许多分子伤害性感受器可以对传入神经元的超敏反应负责。这些实体包括：(I)与刺激传导有关的传入神经元外周末端的受体和感受器；(Ii)控制传入神经元兴奋性和传导特性的离子通道；以及(Iii)在脊髓和脑干的初级传入和二级神经元之间传递信息的递质和递质受体。感觉获得的持续增加可能是由于递质、受体和离子通道表达的变化，受体和离子通道的亚单位组成和生物物理性质的变化，或者传入神经元的结构、连通性和存活率的变化。特定的治疗潜力归因于由传入神经元选择性表达的靶点，其数量和功能在腹部超敏反应中发生改变。新出现的治疗靶点包括瞬时受体潜力(Trp)通道家族的不同成员(TRPV1、TRPV4、TRPA1)、酸敏感离子通道、蛋白酶激活的受体、促肾上腺皮质激素释放因子受体和感觉神经元特异性钠通道。
Inflammation is commonly associated with hyperalgesia. Ideally, this change should abate once inflammation is resolved but this is not necessarily the case because phenotypic changes in the tissue can persist, as appears to be the case in postinfectious irritable bowel syndrome. Basically, all primary afferent neurons supplying the gut can sensitize in response to proinflammatory mediators, and the mechanisms whereby hypersensitivity is initiated and maintained are thus of prime therapeutic interest. There is a multitude of molecular nocisensors that can be responsible for the hypersensitivity of afferent neurons. These entities include: (i) receptors and sensors at the peripheral terminals of afferent neurons that are relevant to stimulus transduction, (ii) ion channels that govern the excitability and conduction properties of afferent neurons, and (iii) transmitters and transmitter receptors that mediate communication between primary afferents and second-order neurons in the spinal cord and brainstem. Persistent increases in the sensory gain may result from changes in the expression of transmitters, receptors and ion channels, changes in the subunit composition and biophysical properties of receptors and ion channels or changes in the structure, connectivity and survival of afferent neurons. Particular therapeutic potential is attributed to targets that are selectively expressed by afferent neurons and whose number and function are altered in abdominal hypersensitivity. Emerging targets of therapeutic relevance include distinct members of the transient receptor potential (TRP) channel family (TRPV1, TRPV4, TRPA1), acid-sensing ion channels, protease-activated receptors, corticotropin-releasing factor receptors and sensory neuron-specific sodium channels.
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影响因子：
--
作者：
Holzer, Peter
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