How Hunger Signals May Override Chronic Pain

Research Highlight by Kurtis Chien

In terms of survival mechanisms, both hunger and pain are incredibly important. Hunger is necessary so that an animal knows when it must eat to refill its energy stores. Pain notifies it of immediate danger and teaches it to avoid similar threats in the future. Sometimes, the two signals can come at odds, and the way that they interact can have great implications in the field of medicine.

Researchers at the University of Pennsylvania were able to demonstrate a hierarchy of signals when both hunger and chronic pain are involved. (1) Food-deprived and well-fed mice were exposed to either acute or chronic pain stimuli. (1) “Chronic” pain was simulated using an injection of Formalin to the paw, which caused inflammation. (1) Data was taken of each mouse’s behavioral responses to pain, since pain is subjective and the researchers could not just ask the mice how much pain they felt. Overall, mice deprived of food prior to exposure to inflammatory pain spent the least amount of time licking and tending to their injured paws.1 A follow-up experiment in which mice were conditioned to associate one side of a testing chamber with inflammatory pain saw well-fed mice avoiding the pain-associated side, while food-deprived mice demonstrated little preference. (1,2)

To discern the pathway responsible for this phenomenon, the researchers stimulated agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus in the brain. (1) These neurons were chosen for study since they are involved in hunger signaling. (3) Selective stimulation revealed that a group of approximately 300 AgRP neurons projecting to the parabrachial nucleus could suppress inflammatory pain responses. (1)

Research on chronic pain is significant because chronic conditions represent one of the greatest burdens on the modern healthcare system. (4) Current treatment methods have some serious flaws, not the least of which include how opiates are prescribed and administered. To exploit this neural circuit could mean a novel form of treatment that may even be able to replace opiates. (2) The fact that the pathway is specific to chronic pain and does not rob an individual of their acute pain response is particularly of interest. (2)

But before any serious talk of treatment methods begins, more research must be conducted on the pathway between the arcuate nucleus and the parabrachial nucleus. The circuit may be promising, but only if further research shows that activation has the same effects on hunger and pain in humans.



  1. Amber L. Alhadeff, Zhenwei Su, Elen Hernandez, Michelle L. Klima, Sophie Z. Phillips, Ruby A. Holland, Caiying Guo, Adam W. Hantman, Bart C. De Jonghe, J. Nicholas Betley. A Neural Circuit for the Suppression of Pain by a Competing Need State. Cell, 2018; 173 (1): 140 DOI: 10.1016/j.cell.2018.02.057
  2. University of Pennsylvania. (2018, March 22). Being hungry shuts off perception of chronic pain. ScienceDaily. Retrieved March 26, 2018 from
  3. Carlson, N. R., & Birkett, M. A. (2017). Physiology of Behavior (12th ed.). Harlow: Pearson.
  4. Loeser, J. D. (2011). Relieving pain in America: A blueprint for transforming prevention, care, education, and research. Washington, D.C: National Academies Press. doi:10.1097/AJP.0b013e318230f6c1