How does the brain encode pain? Scientists uncover neuronal mechanisms in the cortex

A research team at the Institute of Psychology of the Chinese Academy of Sciences, has revealed that parvalbumin (PV) interneurons in the primary somatosensory cortex (S1) preferentially encode pain intensity and drive nociceptive-evoked gamma oscillations (GBOs).

Published online in Neuron on January 13, the study fills a longstanding gap in understanding the origins of nociceptive-evoked GBOs and their selective relationship with pain processing across different species.

The findings suggest the potential for using these oscillations as a promising target for therapeutic interventions.

Pain is a major source of human suffering, resulting in economic costs amounting to hundreds of billions of dollars annually. Accurate assessment and effective treatment of pain are critical yet challenging due to the inherently subjective nature of pain. As a result, researchers have engaged in intense efforts to identify selective neural biomarkers for pain perception.

Previous studies have established that nociceptive-evoked GBOs faithfully encode pain and pain-related behaviors in both humans and animals, suggesting their potential as neural biomarkers.

However, the neuronal mechanisms underlying GBOs have remained poorly understood, limiting the use of GBOs in clinical applications.

To address this problem, Prof. Hu Li and his colleagues conducted a series of cross-species experiments. The experiments featured both nociceptive and non-nociceptive sensory stimuli, a range of neural recording techniques (high-density EEG in humans; and silicon probes and calcium imaging in rodents), and optogenetic methods (both alone and simultaneous with electrophysiology in mice).

Their results confirmed that GBOs in S1 selectively encode pain intensity in humans and are closely linked to spiking activity of PV-positive interneurons in rodents. Calcium imaging indicated that PV interneurons, rather than pyramidal cells, preferentially track pain intensity. Follow-up optogenetic manipulations demonstrated that activating or inhibiting PV interneurons could alter nociceptive-evoked GBOs and related pain-related behaviors.

By linking PV interneuron activity at the microscopic level to GBOs at the mesoscopic level, this research firmly establishes PV interneurons in S1 as the neuronal basis for GBOs’ role in encoding pain intensity.

“These findings are not only significant for understanding the physiology of cortical nociceptive processing but also have far-reaching implications as GBOs are increasingly recognized as a pain biomarker in clinical practice and drug development,” says Prof. Hu.