Sensory root demyelination: Transforming touch into pain

The normal feeling of touch is vital for nearly every aspect of our daily life. However, touching is not always felt as touch, but also abnormally as pain under numerous diseased conditions. For either mechanistic understanding of the faithful feeling of touch or clinical management of chronic pain, there is an essential need to thoroughly dissect the neuropathological changes that lead to painful touch or tactile allodynia and their corresponding cellular and molecular underpinnings. In recent years, we have seen remarkable progress in our understanding of the neural circuits for painful touch, with an increasing emphasis on the upstream roles of non-neuronal cells. As a highly specialized form of axon ensheathment by glial cells in jawed vertebrates, myelin sheaths not only mediate their outstanding neural functions via saltatory impulse propagation of temporal and spatial precision, but also support long-term neuronal/axonal integrity via metabolic and neurotrophic coupling. Therefore, myelinopathies have been implicated in diverse neuropsychiatric diseases, which are traditionally recognized as a result of the dysfunctions of neural circuits. However, whether myelinopathies can transform touch into pain remains a long-standing question. By summarizing and reframing the fragmentary but accumulating evidence so far, the present review indicates that sensory root demyelination represents a hitherto underappreciated neuropathological change for most neuropathic conditions of painful touch and offers an insightful window into faithful tactile sensation as well as a potential therapeutic target for intractable painful touch.