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Spinal somatostatin-positive interneurons transmit chemical itch

Fatima, Mahara; Ren, Xiangyub; Pan, Hailia; Slade, Hannah F.E.a; Asmar, Alyssa J.a; Xiong, Cynthia M.a; Shi, Angelaa; Xiong, Ailin E.a; Wang, Lijinga; Duan, Boa,*

doi: 10.1097/j.pain.0000000000001499
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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 somatostatin-positive (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.

We report the functional synergy of parallel spinal circuits in the transmission of chemical itch and disinhibitory role of pruritic peptide SOM in mediating itch sensation.

aDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, United States

bDana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, MA, United States. Mr. Ren is now with the Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, United States

Corresponding author. Address: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 1105 N. University Ave, Ann Arbor, MI 48109, United States. Tel.: (734) 647-4359. E-mail address: bduan@umich.edu (B. Duan).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received August 31, 2018

Received in revised form December 28, 2018

Accepted January 10, 2019

© 2019 International Association for the Study of Pain
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