Ross Sarah E, Hachisuka Junichi, Todd Andrew J
Itch is a somatosensory percept that is triggered by irritants at the skin’s surface. However, the manner in which itch is coded in the nervous system remains almost completely unknown. Recent work has uncovered a key role of spinal interneurons in the modulation of itch. Here we discuss these recent discoveries in the context of our understanding of spinal microcircuitry, highlighting the possible roles of the dorsal horn in the processing of pruritic input. While it is not known which specific subsets of primary afferents underlie itch, there is good evidence that the main receiving zone for these afferents is within laminae I and II of the spinal cord. For instance, itch sensation is only lost when the conduction of all fibers (including C-fibers) is blocked, implying that itch is mediated in large part by fine diameter fibers, which are known terminate in superficial laminae. In particular, many of these itch-mediating C-fibers are likely to be sensory afferents that express TrpV1 and/or TrpA1, and the primary afferents that express these channels have synaptic connections with lamina I and lamina II neurons (Yang et al. 1998; Nakatsuka et al. 2002; Kosugi et al. 2007; Shim et al. 2007; Imamachi et al. 2009; Uta et al. 2010; Patel et al. 2011; Wilson et al. 2011). As further evidence, neurons in the superficial dorsal horn, show fos induction upon intradermal injection of itch-evoking chemicals such as serotonin and SLIGRL as well as in a dry skin model of pruritus (Nojima et al. 2003, 2004; Akiyama et al. 2009a,b). Last, responses to various pruritogens such as histamine, serotonin, SLIGRL, and chloroquine, as well as the response to mosquito allergy have been recorded from neurons in the superficial dorsal horn (Jinks and Carstens 2000, 2002; Akiyama et al. 2009a,b; Omori et al. 2009; Akiyama et al. 2012c). Together these findings suggest that neurons in the superficial dorsal horn receive the somatosensory input that gives rise to itch sensation. Laminae I and II of the spinal cord contain numerous functional populations of neurons. However, projection neurons that convey information to the brain represent around one percent of the total number of neurons in this region (Todd 2010). Thus, the vast majority of neurons in the superficial dorsal horn are interneurons with local (and in some cases also long propriospinal) axonal projections, and these are involved in the processing of sensory information. Does the existence of a complex network of spinal interneurons imply that itch is decoded within the spinal cord? To what extent is itch modulated in the spinal cord? While we do not yet know the answers to these key questions, there are a number of important psychophysical experiments that are suggestive of the idea that itch is modulated by spinal microcircuits.
瘙痒是一种由皮肤表面的刺激物引发的躯体感觉。然而，瘙痒在神经系统中的编码方式几乎仍然完全未知。最近的研究发现脊髓中间神经元在瘙痒调节中起关键作用。在此，我们结合对脊髓微回路的理解来讨论这些最新发现，重点强调背角在瘙痒性输入处理中的可能作用。虽然尚不清楚哪些特定的初级传入神经子集是瘙痒的基础，但有充分证据表明这些传入神经的主要接收区域在脊髓的I层和II层。例如，只有当所有纤维（包括C纤维）的传导被阻断时，瘙痒感才会消失，这意味着瘙痒在很大程度上是由细直径纤维介导的，已知这些纤维终止于浅层。特别是，许多介导瘙痒的C纤维可能是表达TrpV1和/或TrpA1的感觉传入神经，并且表达这些通道的初级传入神经与I层和II层神经元有突触连接（Yang等人，1998年；Nakatsuka等人，2002年；Kosugi等人，2007年；Shim等人，2007年；Imamachi等人，2009年；Uta等人，2010年；Patel等人，2011年；Wilson等人，2011年）。作为进一步的证据，在皮内注射5-羟色胺和SLIGRL等诱发瘙痒化学物质后以及在瘙痒的干性皮肤模型中，浅层背角的神经元会出现Fos诱导（Nojima等人，2003年、2004年；Akiyama等人，2009a、b）。最后，已经记录到浅层背角神经元对各种致痒原（如组胺、5-羟色胺、SLIGRL和氯喹）的反应，以及对蚊虫过敏的反应（Jinks和Carstens，2000年、2002年；Akiyama等人，2009a、b；Omori等人，2009年；Akiyama等人，2012c）。这些发现共同表明，浅层背角的神经元接收产生瘙痒感的躯体感觉输入。脊髓的I层和II层包含众多功能不同的神经元群体。然而，将信息传递到大脑的投射神经元约占该区域神经元总数的1%（Todd，2010年）。因此，浅层背角的绝大多数神经元是具有局部（在某些情况下也有长的脊髓固有）轴突投射的中间神经元，它们参与感觉信息的处理。脊髓中间神经元的复杂网络的存在是否意味着瘙痒在脊髓内被解码？瘙痒在脊髓中受到多大程度的调节？虽然我们还不知道这些关键问题的答案，但有一些重要的心理物理学实验表明瘙痒是由脊髓微回路调节的。
