A parabrachial hub for need-state control of enduring pain.
\nGoldstein N, Maes A, Allen HN, Nelson TS, Kruger KA, Kindel M, Yeung ATM,
\nSmith NK, Carty JRE, Boccia L, Blank N, Lo E, Villari RE, Cho E, Marble
\nEL, Awh M, Dumiaty Y, Chee MJ, Khanna R, Thaiss CA, Taylor BK, Kennedy A,
\nBetley JN.
\nNature. 2025 Nov;647(8090):689-697. doi: 10.1038\/s41586-025-09602-x.
\nEpub 2025 Oct 8.
\nPMID: 41062698<\/p>\n
Abstract
\nLong-term sustained pain following acute physical injury is a prominent
\nfeature of chronic pain conditions1. Populations of neurons that rapidly
\nrespond to noxious stimuli or tissue damage have been identified in the
\nspinal cord and several nuclei in the brain2-4. Understanding the
\ncentral mechanisms that signal ongoing sustained pain, including after
\ntissue healing, remains a challenge5. Here we use spatial
\ntranscriptomics, neural manipulations, activity recordings and
\ncomputational modelling to demonstrate that activity in an ensemble of
\nanatomically and molecularly diverse parabrachial neurons that express
\nthe neuropeptide Y (NPY) receptor Y1 (Y1R neurons) is increased
\nfollowing injury and predicts functional coping behaviour. Hunger,
\nthirst or predator cues suppressed sustained pain, regardless of the
\ninjury type, by inhibiting parabrachial Y1R neurons via the release of
\nNPY. Together, our results demonstrate an endogenous analgesic hub at
\npain-responsive parabrachial Y1R neurons.<\/p>\n