Mouse Distress Calls Can Trigger Pain in Other Mice

The high-pitched squeaks that mice emit when in pain can cause genuine physical discomfort in other mice who simply hear these distress calls, according to new research from Tokyo University of Science.

The study reveals that exposure to ultrasonic vocalizations alone triggers inflammation in the brain and heightens pain sensitivity, even without any direct physical injury.

Published in PLOS One, the research demonstrates for the first time that emotional pain transmission can occur through sound exposure alone, eliminating other sensory inputs like sight, smell, or direct contact. The findings could reshape understanding of how environmental stress affects pain perception and recovery in medical settings.

Ultrasonic Distress Creates Real Physical Pain

Researchers recorded the ultrasonic portions of distress calls from mice experiencing tail pinching, then played these sounds to naive mice in soundproof chambers. The exposed mice developed measurable hyperalgesia—heightened sensitivity to touch—that persisted for several days.

Using von Frey filaments of varying stiffness to test pain thresholds, scientists found that mice exposed to 4 hours of distress calls at 80 decibels showed significantly decreased pain tolerance on days one and three after exposure. The effect disappeared by day seven, suggesting temporary but substantial impact.

“In this study, we demonstrate for the first time that ultrasonic vocalizations emitted by mice in response to pain stimuli induce emotional transmission and hyperalgesia in other mice,” explained Assistant Professor Satoka Kasai, who led the research. “These mice exhibit hypersensitivity that arises without injury or direct painful stimulation but is instead triggered by exposure to sound stress.”

Brain Inflammation Drives Sound-Induced Pain

DNA microarray analysis of brain tissue revealed the biological mechanism behind this phenomenon. Sound stress exposure triggered significant changes in gene expression within the thalamus, the brain region where pain signals are processed before reaching conscious awareness.

The analysis identified 444 upregulated genes and 231 downregulated genes, with many linked to inflammatory responses. Two genes showed particularly dramatic increases: prostaglandin-endoperoxidase synthase 2 (increased 17.3-fold) and C-X-C motif chemokine ligand 1 (increased 14.1-fold).

Key Research Findings:

• Sound stress alone decreased pain thresholds for up to three days
• Brain inflammation genes increased dramatically after ultrasonic exposure
• Anti-inflammatory drugs reversed sound-induced pain sensitivity
• Distress calls prolonged recovery in mice with existing inflammatory pain
• Effects occurred without visual, olfactory, or tactile contact between mice

Treatment Implications for Chronic Pain

The researchers tested whether anti-inflammatory medications could counteract sound-induced hyperalgesia. Both loxoprofen (a COX-2 inhibitor) and SB225002 (a chemokine receptor antagonist) significantly reduced pain responses when administered after sound stress exposure.

Perhaps more concerning, when mice with pre-existing inflammatory pain were exposed to distress calls, their recovery period extended significantly. While normal inflammatory pain typically resolved within 14 days, sound-stressed mice showed prolonged sensitivity lasting 21 days.

The effectiveness of pain-relieving medications was also compromised in sound-stressed animals, suggesting that environmental noise could interfere with treatment outcomes in clinical settings.

Environmental Stress and Medical Recovery

The study’s implications extend beyond laboratory observations to real-world medical environments. Hospital sounds, including alarms, machinery, and patient distress, might inadvertently worsen pain and delay recovery through similar neuroinflammatory pathways.

“In addition to inducing inflammation in the brain that leads to hyperalgesia, sound stress also exacerbates inflammatory pain and may interfere with pain-relieving treatments,” Kasai noted. “Our research can help improve the understanding of stress-related pain and guide the development of new, scientifically based pain management treatment strategies.”

The research involved carefully controlled conditions where mice heard only ultrasonic frequencies above 20 kilohertz—sounds inaudible to humans but well within the hearing range of mice, which can detect frequencies up to 100 kilohertz.

While the study focused on mice, the findings suggest that auditory stress might influence pain perception across species. The research highlights how social and environmental factors can create genuine physiological changes that complicate pain management and recovery processes.

Future research will examine whether specific sound frequencies or the emotional content of vocalizations drives these effects, potentially leading to acoustic interventions that could either minimize harmful sound stress or even promote healing in medical environments.