A Neural Circuit for the Suppression of Pain by a Competing Need State

Cell. 2018 Mar 22;173(1):140-152.e15. doi: 10.1016/j.cell.2018.02.057.


Hunger and pain are two competing signals that individuals must resolve to ensure survival. However, the neural processes that prioritize conflicting survival needs are poorly understood. We discovered that hunger attenuates behavioral responses and affective properties of inflammatory pain without altering acute nociceptive responses. This effect is centrally controlled, as activity in hunger-sensitive agouti-related protein (AgRP)-expressing neurons abrogates inflammatory pain. Systematic analysis of AgRP projection subpopulations revealed that the neural processing of hunger and inflammatory pain converge in the hindbrain parabrachial nucleus (PBN). Strikingly, activity in AgRP → PBN neurons blocked the behavioral response to inflammatory pain as effectively as hunger or analgesics. The anti-nociceptive effect of hunger is mediated by neuropeptide Y (NPY) signaling in the PBN. By investigating the intersection between hunger and pain, we have identified a neural circuit that mediates competing survival needs and uncovered NPY Y1 receptor signaling in the PBN as a target for pain suppression.

Keywords: AgRP neurons; analgesia; calcium imaging; hunger; inflammation; neuropeptide Y; nociception; optogenetics; pain; parabrachial nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism
  • Analgesics, Opioid / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Behavior, Animal / drug effects
  • Diet
  • Feeding Behavior / drug effects
  • Formaldehyde / toxicity
  • Glutamate Decarboxylase / metabolism
  • Locomotion / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Morphine / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pain / etiology
  • Pain / metabolism
  • Pain / pathology*
  • Parabrachial Nucleus / drug effects
  • Parabrachial Nucleus / metabolism
  • Receptors, Neuropeptide Y / metabolism
  • Signal Transduction


  • Agouti-Related Protein
  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Receptors, Neuropeptide Y
  • neuropeptide Y-Y1 receptor
  • Formaldehyde
  • Morphine
  • Glutamate Decarboxylase