The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons
The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons
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DOI：
10.1523/jneurosci.2862-07.2007
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发表时间：
2007-09-12
影响因子：
5.3
通讯作者：
Giesler, Glenn J., Jr.
中科院分区：
文献类型：
--
作者：
Davidson, Steve;Zhang, Xijing;Giesler, Glenn J., Jr.
瘙痒是一种日常感觉，但当与疾病或感染有关时，它可能是慢性的，使人虚弱。一些形式的瘙痒可以用抗组胺药阻断，但其他不能，这构成了一个重要的临床问题。关于非组胺能机制产生的瘙痒机制的信息很少。我们研究了脊髓丘脑束神经元对组胺能和非组胺能形式的瘙痒刺激的反应。采用反激激活技术鉴定了57个灵长类动物的脊髓丘脑束（STT）神经元，并检测了它们对组胺和奶牛的反应，奶牛是覆盖在豆科植物Mucuna pruriens豆荚上的非组胺性瘙痒针状体。每个被检查的神经元在后肢多毛的皮肤上都有一个接受野，并对有害的机械刺激做出反应。我们对STT神经元随机使用两种止痒剂进行了测试，发现12种对组胺有反应，7种对奶牛有反应。每个瘙痒素反应的STT神经元都被化学热原辣椒素激活，三分之二的STT神经元对有害的热刺激有反应，这表明这些神经元也传递化学、热和机械伤害性信息。组胺或奶牛反应性STT神经元在边缘区和深背角均有发现，属于高阈值和宽动态范围。出乎意料的是，组胺和奶牛从来没有激活过同一个细胞。我们的结果表明，脊髓丘脑束包含对组胺或非组胺性瘙痒产生剂奶牛有反应的相互排斥的神经元群。
Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage.