A newly described cell type that forms a network in the skin plays a central role in sensing mechanical input and in initiating the sensation of pain.
Pain is an experience manifested in the brain when noxious stimuli received from peripheral sites in the body are interpreted as potentially dangerous. Peripheral nerves responsible for initiating these signals are aptly termed nociceptive nerves or nociceptors. The nociceptors in the skin are described to have free nerve endings because they are bare, and not protected by the myelin-sheaths of glial Schwann cells that surround most other nerves. Instead, they have been found to associate with Remak Schwann cells that don’t myelinate but do metabolically support the nerve cell.1 A paper recently published in Science magazine sheds new light on these pain-associated fibers and the supportive cells they choose to associate with.2
Using engineered mouse lines expressing reporters in both the nociceptors and glial Schwann cells, the researchers uncovered a web-like network made up of a newly defined type of supportive cells, dubbed “nociceptive Schwann cells”. To determine whether this network apart from being locally associated with the nociceptors, also contributes to their signaling, behavioral tests were carried out in mice. Stimulation of the nociceptive Schwann cells was sufficient to elicit apparent pain responses in the test animals, proving that the glial cells have independent signaling properties. To elucidate their innate signaling role, subthreshold activation of the nociceptive Schwann cells was combined with noxious stimuli such as cold, heat or mechanical input. In this way, the mice could be sensitized towards all three modal inputs tested, but only responses to mechanical input was influenced when the Schwann cells were inhibited. Specialized recordings of electrical signals confirmed that the nociceptive Schwann cells are sensitive to changes in mechanical force but much less to sustained mechanical input.
This study thus identified a “glio-neural” complex of nociceptive nerves and Schwann cells in the form of a mesh-like cellular structure underneath the skin that has a central role in pain sensation. The nociceptive Schwann cells, which are a specialized type of Remak Schwann cells, were shown to have their own signaling properties and to be particularly sensitive to mechanical stimulation. This fundamentally novel concept will potentially contribute to current and future research into pain and its treatment.
- Harty BL, Monk KR. Curr Opin Neurobiol. 2017 Dec;47:131-137.
- Abdo H, Calvo-Enrique L, Lopez JM, Song J, Zhang MD, Usoskin D, El Manira A, Adameyko I, Hjerling-Leffler J, Ernfors P. Science. 2019 Aug 16;365(6454):695-699.