Neuropeptide Y in itch regulation

A spinal neural circuitry for converting touch to itch sensation

“…Most importantly, our finding is consistent with the observation that Grpr neurons express Npy1r ( Supplementary Fig. 4g, h), as well as recent pharmacological studies showing that exogenous NPY or NPY1R agonist inhibit chemical itch 28,29 . The present finding is further consistent with the observation of augmented alloknesis in a mouse model of dry skin itch 21,26,27,31,42 .…”

“…In view of the present findings that Npy1r is expressed in GRPR neurons ( Supplementary Fig. 4g, h), it is conceivable that exogenous administration of NPY or NPY1R agonists in the spinal cord can activate NPY1R to inhibit the function of GRPR neurons and thus inhibit both chemical and mechanical itch 28,29 . Since not all GRPR neurons express NPY1R, the inhibitory effect of NPY or NPY1R agonists on chemical itch could depend on the type of pruritogens or subtypes of GRPR neurons expressing NPY1R.…”

“…While mechanical itch and chemical itch have been considered to function through distinct neuronal pathways in the spinal cord 26 , 27 , 46 , recent studies showed that NPY–NPY1R signaling can inhibit both mechanical and chemical itch, indicating that they may share the same pathway 28 , 29 . The finding that ablation of GRPR neurons significantly reduced the scratching behavior evoked by optoactivation of Tac2 ChR2 neurons prompted us to examine whether mechanical itch transmission is dependent on GRPR neurons.…”

“…Therefore, a key prerequisite for evaluating whether mechanical itch depends on GRPR neurons is to ablate GRPR neurons completely, manifesting in the absence of CQ-evoked scratching behavior 6 . Recent studies have shown that pharmacological activation of spinal NPY1R can inhibit both mechanical 27 and chemical itch 28,29 . This promoted us to examine to what extent Npy1r and Grpr or Tac2 are co-expressed in the spinal cord using RNAscope.…”

“…The spinal neurons expressing neuropeptide Y (NPY) and its receptor NPY receptor 1 (NPY1R) have been shown to be important for gating mechanical itch 21,27 . On the other hand, recent studies have also implicated the NPY-NPY1R signaling in inhibition of chemical itch 28,29 , raising the possibility that mechanical itch is converged on GRPR neurons. Piezo-2, a mechanotransduction ion channel in Merkel cell complex 30 , acts as an inhibitory channel for gating touch-to-itch conversion, as well as aging-associated alloknesis 31 .…”