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

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.

SUBMITTER: Agostinelli LJ 

PROVIDER: S-EPMC8009815 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature