Novel brain circuits that mediate interactions between pain and stress

Chronic pain and mental are inextricably linked; study sheds light on the interactions between pain and stress at the level of neural circuits in the brain and spinal cord in mice (Illustration: Asmita Sarkar, Srishti Manipal Institute of Art, Design, and Technology)

Pain and stress are tightly linked. Patients suffering from chronic pain often suffer from stress and anxiety, while persistent anxiety can make pain worse. However, how exactly these two clinically challenging conditions interact in the brain is poorly understood.

In a new study published in eLife, researchers at the Centre for Neuroscience, led by Arnab Barik, used cutting-edge mouse genetic and optogenetic techniques to map out a neural network that stretches from a small structure in the front of the brain called the lateral septum to the spinal cord. The network includes structures in the hypothalamus and hindbrain nuclei.

They show that when mice are exposed to stress, a cascade of neural activity in the lateral septum ensues. The lateral septum, in turn, shuts down neurons in the hypothalamus, which consequently affects the downstream activity in the brainstem and spinal cord affecting pain sensation.

 This work can have long-term implications for how interactions between pain and stress are understood. It can also help in the development of novel therapeutics that can restrict stress-induced exacerbation of chronic pain.

Using intersectional viral strategies to label functional synapses, the study shows that the lateral septum, lateral hypothalamus, and ventromedial medulla are interconnected. These regions are known to mediate effects of pain and stress (Image courtesy: Arnab Barik)



 Shah DP, Sharma PR, Agarwal R, Barik A, The lateral septum plays a transforming role in acute stress-induced analgesia, eLife (2024).

Reddy P, Chaterji S, Varughese A, Chaudhary Y, Sathyamurthy A, Barik A, Converging inputs compete at the lateral parabrachial nuclei to dictate the affective-motivational responses to cold pain, bioRxiv (2024).

Reddy P, Vasudeva J, Shah D, Prajapati JN, Harikumar N, Barik A, A deep-learning driven investigation of the circuit basis for reflexive hypersensitivity to thermal pain, Neuroscience (2023).

Funded by SERB-CRG, India Alliance Intermediate Fellowship and IISc.