Itch and pain differences and commonalities.

Pain and itch are generally regarded antagonistic as painful stimuli such as scratching suppresses itch. Moreover, inhibition of pain processing by opioids generates itch further supporting their opposing role. Separate specific pathways for itch and pain processing have been uncovered, and several molecular markers have been established in mice that identify neurons involved in the processing of histaminergic and non-histaminergic itch on primary afferent and spinal level. These results are in agreement with the specificity theory for itch and might suggest that pain and itch should be investigated separately on the level of neurons, mediators, and mechanisms. However, in addition to broadly overlapping mediators of itch and pain, there is also evidence for overlapping functions in primary afferents: nociceptive primary afferents can provoke itch when activated very locally in the epidermis, and sensitization of both nociceptors and pruriceptors has been found following local nerve growth factor application in volunteers. Thus, also mechanisms that underlie the development of chronic itch and pain including spontaneous activity and sensitization of primary afferents as well as spinal cord sensitization may well overlap to a great extent. Rather than separating itch and pain, research concepts should therefore address the common mechanisms. Such an approach appears most appropriate for clinical conditions of neuropathic itch and pain and also chronic inflammatory conditions. While itch researchers can benefit from the large body of information of the pain field, pain researchers will find behavioral readouts of spontaneous itch much simpler than those for spontaneous pain in animals and the skin as source of the pruritic activity much more accessible even in patients.