Researchers reveal how brain amplifies perception of pain from multiple sources

When pain strikes from multiple sources—such as a paper cut followed by contact with hot water—the experience can feel disproportionately intense. But is this agony merely additive, or does the brain integrate these signals in a way that amplifies suffering?

Researchers have long known that pain is highly subjective and is influenced not only by the intensity of harmful stimuli but also by cognitive factors, such as instructions on how to perceive pain. However, how the brain integrates different pain signals into a unified experience—especially in complex scenarios involving multimodal pain—was previously not well understood.

Now, though, a new study published in Proceedings of the Royal Society B has uncovered how the human brain's perception of pain is influenced by instructions—such as whether to perceive pain as separate sensations or as integrated multimodal pain. The study also reveals how this process works and identifies the neural mechanisms involved.

Led by Dr. KONG Yazhuo from the Institute of Psychology of the Chinese Academy of Sciences, a research team has discovered that multimodal pain integration in the brain—rather than somatosensory inputs such as touch, warm sensation—significantly enhances overall pain perception when participants are instructed on how to perceive the pain. The researchers also discovered that this integration was encoded by the precuneus—a region of the brain tucked between the two cerebral hemispheres, just behind the posterior cingulate cortex.

The researchers designed a series of experiments in which participants were exposed to heat, pressure, and electrical stimuli. These were delivered either individually (single-modal) or in combination (bimodal), with or without accompanying perceptual instructions directing participants to focus on the overall pain experience. Brain activity was recorded using functional magnetic resonance imaging (fMRI). Participants' subjective pain ratings were also collected.

Results showed that participants reported significantly higher pain levels when they were instructed to focus on overall pain during bimodal stimulation rather than when the instruction was absent. Interestingly, this enhancement in perceived pain also vanished in trials involving sub-threshold, non-painful stimuli. These findings suggest that the integrative amplification effect relies heavily on top-down cognitive influences rather than the additive nature of stimuli.

The precuneus emerged as a key hub in the multimodal pain integration process. The study observed a significant positive correlation between the magnitude of the blood-oxygen-level-dependent (BOLD) response in the precuneus and the degree of integration in pain ratings.

Furthermore, strong similarities were found between the brain activity in the precuneus and participants' pain perception, suggesting that the precuneus plays a vital role in integrating pain information into a cohesive and intensified pain experience.

The study demonstrates the key role the precuneus plays in the multimodal pain integration process as well as the significant enhancement of overall pain perception under instructions to perceive pain in an integrated way.

"These findings provide a theoretical foundation for multi-target interventions aimed at addressing complex pain syndromes," said Dr. KONG. "Recognizing how perceptual context shapes pain integration can inform clinical approaches, especially for complex or masked pain syndromes."

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