Journal
PAIN
Volume 160, Issue 5, Pages 1166-1174Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000001499
Keywords
Itch spinal circuit; SOM interneurons; Npra
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Funding
- Department of Molecular, Cellular, and Developmental Biology, University of Michigan
- Neuroscience Scholar Program, University of Michigan
- M-Cubed Program, University of Michigan
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Recent studies have made significant progress in identifying distinct populations of peripheral neurons involved in itch transmission, whereas the cellular identity of spinal interneurons that contribute to itch processing is still a debate. Combining genetic and pharmacological ablation of spinal excitatory neuronal subtypes and behavioral assays, we demonstrate that spinal somatostatinpositive (SOM+) excitatory interneurons transmit pruritic sensation. We found that the ablation of spinal SOM+/Lbx1(+) (SOMLbx1) neurons caused significant attenuation of scratching responses evoked by various chemical pruritogens (chemical itch). In an attempt to identify substrates of spinal itch neural circuit, we observed that spinal SOM+ neurons partially overlapped with neurons expressing natriuretic peptide receptor A (Npra), the receptor of peripheral itch transmitter B-type natriuretic peptide. Spinal SOM+ neurons, however, did not show any overlap with itch transmission neurons expressing gastrin-releasing peptide receptor in the dorsal spinal cord, and the gastrin-releasing peptide-triggered scratching responses were intact after ablating spinal SOM+ neurons. Dual ablation of SOMLbx1 and Npra(+) neurons in the spinal cord reduced chemical itch responses to a greater extent than ablation of SOMLbx1 or Npra(+) neurons alone, suggesting the existence of parallel spinal pathways transmitting chemical itch. Furthermore, we showed that SOM peptide modulated itch processing through disinhibition of somatostatin receptor 2A-positive inhibitory interneuron. Together, our findings reveal a novel spinal mechanism for sensory encoding of itch perception.
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