Pain Can Be Transmitted Through Sound Alone

Pain is more than a direct response to physical injury. It is a multifaceted experience that includes emotional and sensory components. Psychological stress, including exposure to others in pain, has been shown to intensify pain responses in animals. One such example is the 'bystander effect' in mice, where individuals co-housed with mice experiencing inflammatory pain also develop heightened sensitivity to pain, or hyperalgesia. However, the mechanisms behind this social transfer of pain are not well understood.

A recent study by researchers at Tokyo University of Science explores how ultrasonic vocalizations–high-frequency sounds emitted by rodents–may contribute to this phenomenon. The findings, published in PLOS One, reveal that these vocal signals alone are sufficient to induce hyperalgesia in otherwise unaffected mice.

Ultrasonic signals linked to pain transmission

Mice produce ultrasonic vocalizations in response to a range of stimuli, including pain. These signals are typically inaudible to humans. In the new study, researchers recorded ultrasonic sounds emitted by mice exposed to pain-inducing stimuli and isolated these sounds from other environmental cues. They then played the recordings to naïve mice housed in a soundproof environment to ensure that only the ultrasonic vocalizations were perceived.

The effect was measured using von Frey filaments–tools that apply a range of mechanical pressure to the hind paw–to assess changes in pain thresholds. Mice exposed to the sound stimuli exhibited lower withdrawal thresholds, consistent with an increased sensitivity to pain.

Gene expression changes reveal potential molecular drivers

To explore the biological mechanisms that might underpin this phenomenon, the team conducted a microarray analysis of brain tissue from mice exposed to the recorded vocalizations. This approach allows researchers to observe broad patterns in gene activity.

Results showed significant changes in gene expression: 444 genes were upregulated and 231 were downregulated. Notably, genes involved in inflammatory processes were affected. These included prostaglandin-endoperoxidase synthase 2 and C-X-C motif chemokine ligand 1. Further analysis linked the differentially expressed genes to inflammatory pathways, such as responses to lipopolysaccharides and activation of tumor necrosis factor signaling.

Anti-inflammatory treatments reduce sound-induced pain responses

In a subsequent experiment, researchers evaluated whether the pain sensitivity induced by sound exposure could be reduced through pharmacological intervention. Mice were administered anti-inflammatory agents after being subjected to the sound stimuli. The treatment significantly mitigated the observed hyperalgesia.

The researchers also examined whether sound exposure could exacerbate inflammatory pain. In a model where mice had been induced with inflammation, exposure to ultrasonic vocalizations prolonged the pain response. Again, anti-inflammatory drugs attenuated the effect, reinforcing the connection between sound stress and inflammation-linked pain.

Implications for understanding social modulation of pain

This study demonstrates that pain-related vocalizations can act as social stressors capable of eliciting measurable changes in pain perception. By removing other sensory cues–such as sight, smell or touch–the research isolates auditory communication as a sufficient trigger for stress-related pain enhancement.

These findings suggest that social or environmental sound cues may influence pain perception and persistence. While this work was conducted in mice, it raises important considerations for animal housing conditions and medical environments, where ambient sound could affect well-being and recovery.

Further research is needed to determine how different sound qualities and frequencies affect brain regions involved in emotional and pain processing. Understanding these pathways may also contribute to the development of new strategies for managing stress-induced pain.

Reference: Kasai S, Ukai S, Kuroda J, et al. Pain-stimulated ultrasound vocalizations and their impact on pain response in mice. Mishra SK, ed. PLoS One. 2025;20(7):e0324730. doi: 10.1371/journal.pone.0324730

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