Abstract
A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli. Ablation of NMBR neurons partially attenuated peripherally induced itch without compromising nociceptive processing. Importantly, electrophysiological studies suggested that GRPR neurons receive glutamatergic input from NMBR neurons. Thus, we propose that NMB and GRP may transmit discrete itch information and NMBR neurons are an integral part of neural circuits for itch in the spinal cord.
Highlights
The spinal cord dorsal horn is comprised of multiple micro neural circuits, which may function through cascades, in parallel, or in an overlapping manner
This could be attributed to disruption of cis-regulatory elements in the Nmb gene required for appropriate expression of eGFP
It is worth noting that irrespective of the concentration of Neuromedin B (NMB) application, we found that a significant percentage of eGFP+ neurons did not respond to NMB, consistent with the observation that some eGFP+ neurons remained after NMB-sap treatment
Summary
The spinal cord dorsal horn is comprised of multiple micro neural circuits, which may function through cascades, in parallel, or in an overlapping manner. Spinal neuronal ablation and behavioral studies suggested that spinal GRPR neurons constitute a central itch-specific circuit[7,13,14,15,16]. Behavioral studies suggested that NMB acts exclusively through NMBR to relay itch information, whereas GRP can cross-activate NMBR as well in the spinal cord[12]. We studied the role of NMBR neurons in itch and pain and their relation with GRPR neurons using behavioral and electrophysiological approaches. Our studies suggest that spinal NMB-NMBR and GRP-GRPR pathways encode discrete itch information. Our data suggest that NMBR neurons may function upstream of GRPR neurons via glutamatergic transmission
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