Circuit dissection of the role of somatostatin in itch and pain (original) (raw)

Huang, J. et al. (2018) Circuit dissection of the role of somatostatin in itch and pain.Nature Neuroscience, 21(5), pp. 707-716. (doi: 10.1038/s41593-018-0119-z) (PMID:29556030) (PMCID:PMC5923877)

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Abstract

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide.

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Funder and Project Information

1

Spinal inhibitory interneurons that suppress itch

Andrew Todd

MR/L003430/1

INP - CENTRE FOR NEUROSCIENCE

1

The role of NPY-containing inhibitory interneurons in spinal pain pathways

Andrew Todd

BB/N006119/1

INP - CENTRE FOR NEUROSCIENCE

1

Defining pain circuitry in health and disease

Andrew Todd

102645/Z/13/Z

INP - CENTRE FOR NEUROSCIENCE

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