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Novel inhibitory brainstem neurons with selective projections to spinal lamina I reduce both pain and itch
Journal article   Open access   Peer reviewed

Novel inhibitory brainstem neurons with selective projections to spinal lamina I reduce both pain and itch

Lindsay J Agostinelli and Alexander G Bassuk
Journal of comparative neurology (1911), Vol.529(8), pp.2125-2137
06/2021
DOI: 10.1002/cne.25076
PMCID: PMC8009815
PMID: 33247430
url
https://doi.org/10.1002/cne.25076View
Published (Version of record) Open Access

Abstract

Sensory information is transmitted from peripheral nerves, through the spinal cord, and up to the brain (“bottom up” pathway). Some of this information may be modulated by “top‐down” projections from the brain to the spinal cord. Discovering endogenous mechanisms for reducing pain and itch holds enormous potential for developing new treatments. However, neurons mediating the top‐down inhibition of pain are not well understood, nor has any such pathway been identified for itch sensation. Here, we identify a novel population of GABAergic neurons in the ventral brainstem, distinguished by prodynorphin expression, which we named LJA5. LJA5 neurons provide the only known inhibitory projection specifically to lamina I of the spinal cord, which contains sensory neurons that transmit pain and itch information up to the brain. Chemogenetically activating LJA5 neurons in male mice reduces capsaicin‐induced pain and histamine‐induced itch. Identifying this new pathway opens new treatment opportunities for chronic, refractory pain, and pruritis. We identified a novel population of inhibitory prodynorphin neurons in the brainstem which we named LJA5. LJA5 neurons selectively target lamina I of the spinal cord, and other sensory nuclei including the lateral parabrachial and periaqueductal gray. Activation of LJA5 neurons reduces pain and itch.
dynorphin histamine chemogenetic anterograde tracing prodynorphin RRID: AB_11213126 LJA5 RRID:AB_2631318 capsaicin lamina I activation RRID AB_11180610 RRID: AB_262156 stimulation

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