ABSTRACT
Afferent nerve fibers dedicated to pain and to itch have been hypothesized in the late nineteenth and early twentieth centuries. Opioid-induced itch has often been linked to peripheral release of histamine from mast cells as intradermally injected opioids can activate mast cells by a non-receptor-mediated mechanism. The pure spatial pattern of activated nociceptors might similarly underlie the itch sensation without any requirement of itch-specific primary afferent neurons. Based on the close interactions between keratinocytes and sensory nerve endings in the epidermis, the cross talk between them changes in keratinocyte differentiation, and mediator release based on changes in opioid signaling appears sufficient to cause sensitization and activation of the sensory nerves and thus underlie skin symptoms of itch and pain reported in sensitive skin. Interestingly, lysophosphatidic acid has been linked to the mechanisms of neuropathic pain. In particular, specific markers for pruriceptors and first biomarkers for pain and itch have been found.
