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Novel inhibitory brainstem neurons with selective projections to spinal lamina I reduce both pain and itch
Author(s) -
Agostinelli Lindsay J.,
Bassuk Alexander G.
Publication year - 2021
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.25076
Subject(s) - brainstem , neuroscience , inhibitory postsynaptic potential , spinal cord , sensory system , biology , gabaergic , nociception , population , medicine , receptor , environmental health , biochemistry
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.