Fig. 9: Schematics showing the spinal neural circuitry for touch-to-itch conversion.
From: A spinal neural circuitry for converting touch to itch sensation
a Under naive condition, Tac2/Ucn3tdTom neurons in lamina IIIo receive innocuous light touch information via LTMR Aβ/TLR5 fibers directly and in turn relay the touch information to GRPR neurons in laminae I–IIo, which convert it to itch. By contrast, Tac2/Ucn3tdTom neurons in lamina IIi which receive direct inputs from C/Aδ fibers and indirect Aβ inputs may remain silent or inactive resulting from feedforward inhibition of GABAergic/glycinergic neurons. b Under dry skin itch condition, GRP primary afferents convey chemical itch information via GRP to GRPR neurons directly. In addition, enhanced chemical itch relayed by C/Aδ fibers recruit IIi Tac2/Ucn3tdTom neurons to relay chemical itch information to GRPR neurons. Light touch information conveyed by Tac2/Ucn3tdTom neurons, along with newly recruited IIi Tac2/Ucn3tdTom neurons, and chemical itch converge on GRPR neurons. Augmented activity of GRPR function can also be resultant from reduced or a loss of feedforward inhibition mediated by GABAergic/glycinergic neurons, giving rise to exacerbated chronic itch and alloknesis.
