Post-Traumatic Neuropathic Pain: The Role Of The Skin

In the past decades, a body of evidence has shown that the uppermost layer of the skin, the epidermis, not only serves as a protective layer but also plays a pivotal role in the transmission of painful and non-painful stimuli to the central nervous system. The epidermis consists of five layers (Fig. 1): stratum basale, stratum spinosum, stratum granulosum, stratum lucidum (only in palmar and plantar skin) and stratum corneum, from the inner-most to the outer-most layer, respectively. The epidermis contains keratinocytes, which undergo gradual differentiation as they progress from the basal layer to the stratum corneum, with a turnover time of about 27 days. Keratinocytes relay sensory information as they are activated by mechanical, thermal and noxious stimuli and they transmit their information indirectly to the spinal cord by activating nearby located peripheral nerve fibers . For example, upon activation, keratinocytes secrete adenosine triphosphate (ATP), which binds to and activates P2X purinoceptor 3 (P2X3), receptors expressed on adjacent epidermal nerve fibers. In addition to keratinocytes, the epidermis contains Merkel cells, melanocytes and Langerhans cells, all of which serve different sensory purposes (Fig. 1). Merkel cells are believed to play a prominent role in the transduction of light touch . Melanocytes are UV sensitive cells that produce melanin, a pigment that has photo protectant properties. Langerhans cells are antigen-presenting cells, but are also sensitive to thermal stimulation, such as the increasing skin temperature occurring during local inflammation.

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