Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
J Neurosci. 2011 Oct 19;31(42):14841-9. doi: 10.1523/JNEUROSCI.3005-11.2011.
Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: (1) a selective conduction block in myelinated fibers substantially reduces itch in a subgroup of subjects with A-fiber-dominated itch, (2) the time course of itch sensation differs between subjects with A-fiber- versus C-fiber-dominated itch, (3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, (4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, (5) the time of peak itch sensation for subjects with A-fiber-dominated itch matches the time for peak response in myelinated fibers, and (6) the time for peak itch sensation for subjects with C-fiber-dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that nonhistaminergic itch is mediated through activity in both unmyelinated and myelinated afferents.
尽管瘙痒感具有重要的临床意义，但人们对其潜在的神经机制仍知之甚少。在许多疾病中，抗组胺药并不能有效治疗瘙痒，这表明存在非组胺能机制。为了研究小髓鞘传入纤维在非组胺能瘙痒中的作用，我们在人体心理物理学研究中测试了差异神经阻滞对牛痘植物刺毛（Mucuna pruriens）插入皮内引起的瘙痒的影响。在麻醉猴的电生理实验中，我们研究了不同化学刺激（牛痘刺毛、组胺、辣椒素）对皮肤、伤害性、髓鞘传入纤维的反应。我们的研究结果提供了几条证据，表明髓鞘纤维在牛痘引起的瘙痒中起着重要作用：（1）髓鞘纤维的选择性传导阻滞可显著减轻以 A 纤维为主的瘙痒的瘙痒感；（2）以 A 纤维为主的瘙痒和以 C 纤维为主的瘙痒的瘙痒感时间进程不同；（3）牛痘激活了猴的一小部分髓鞘和无髓鞘传入纤维；（4）对牛痘的反应时间在髓鞘纤维和无髓鞘纤维中不同；（5）以 A 纤维为主的瘙痒的受试者的瘙痒感峰值时间与髓鞘纤维的峰值反应时间相匹配；（6）以 C 纤维为主的瘙痒的受试者的瘙痒感峰值时间与无髓鞘纤维的峰值反应时间相匹配。这些发现表明，伤害性、髓鞘传入纤维的活动有助于牛痘引起的感觉，非组胺能瘙痒是通过无髓鞘和髓鞘传入纤维的活动介导的。
