Amygdala: a piece in the puzzle of pain

The almond-shaped brain region amygdala is a key regulator of fear and reward – with a wealth of associated emotions. An international team of scientists around IMP Group Leader Wulf Haubensak now showed that the amygdala also modulates how pain is represented in the brain.

Experiencing pain on the level of the brain is a complex phenomenon and requires the activation and modulation of many different networks of neurons. In a study now published online in the journal Communications Biology, IMP scientists and collaborators identified a central structure and mechanism that turns pain into an experience.

Scientists have long had a detailed understanding of how a small, almond-shaped brain region called amygdala centrally controls behaviours associated with fear and reward. The amygdala plays this central role by controlling connections between local and global networks of neurons. Wulf Haubensak and his collaborators stepped aside of the established “fear-reward” mechanisms and turned their attention to other, related brain states, such as intuitive “gut feelings”, or – pain.

To see how the amygdala acts on local networks to modulate large brain states, the scientists combined two sophisticated methods: functional magnetic resonance imaging (fMRI) allows to image the interaction of brain regions throughout the whole brain network; and optogenetics, through which light-sensitive proteins are formed in specific circuits in a brain region that can then be activated with light impulses.

The scientists applied these methods on a subset of neurons in the amygdala of mice. The local interactions of these subsets adapt to “pain signals” by adjusting brain-wide networks: while one subset modulates whether the brain allows or even enhances the signal in the lower-order “local” network, the other subset “dampens” the pain-signal in the higher-order more global brain regions later in the activity cascade.

The findings are the outcome of basic research and there is no immediate clinical relevance, but the importance of understanding how pain is processed in people‘s brains is obvious – painkillers and other therapies could benefit from it. “We know for example that there is a link between traumatic experiences and increased sensitivity to pain”, says Wulf Haubensak. “Principles such as the amygdala mechanisms that we described could help find the underlying cause for the conditions of such patients.” Andreas Hess, a collaborator from Friedrich-Alexander-University of Erlangen-Nürnberg who also works with humans, adds: “Since we have carved out our findings using fMRI, they have a high translational potential - as we have already seen in previous  studies.”

Image caption: Central amygdala circuits modulates aversive pain states across global brain networks. Heat colormap indicates intensity of aversive signals.  

Further Reading
Wulf Haubesak's lab at the IMP
Andreas Hess' lab at Friedrich-Alexander-University of Erlangen-Nürnberg

***

Original Publication
“Central amygdala circuitry modulates nociceptive processing through differential hierarchical interaction with affective network dynamics.” 
Isabel Wank, Pinelopi Pliota, Sylvia Badurek, Klaus Kraitsy, Joanna Kaczanowska, Johannes Griessner, Silke Kreitz, Andreas Hess, Wulf Haubensak. Communications Biology, published online. DOI: 10.1038/s42003-021-02262-3