A call to the mouse in distress can cause pain in other mice

According to new research from Tokyo University of Science, the high-sharp screams from mice during pain can cause real physical discomfort in other mice.

The study shows that exposure to ultrasound alone, even without any direct physical damage, can trigger inflammation in the brain and enhance pain sensitivity.

The study, published on PLOS One, demonstrates for the first time that emotional pain transmission can occur through sound exposure alone, eliminating other sensory inputs such as vision, odor, or direct contact. These findings can reshape understanding of how environmental stress affects pain and recovery in a medical environment.

Ultrasound death can cause real physical pain

The researchers recorded ultrasonic parts from mice sewn on their tails and then played the sounds in the soundproofing room. The exposed mice developed measurable hyperalgesia (sensitivity to touch) for several days.

The scientists used von Frey filaments to test the pain threshold and found that mice exposed to a 4-hour distress call at 80 decibels were significantly reduced in pain tolerance on the first and third days after exposure. The effect disappeared on day seven, indicating a temporary but significant impact.

“In this study, we demonstrate for the first time that ultrasound sounding in mice in response to pain stimulation can cause emotional transmission and hyperalgesia in other mice,” he said. Assistant Professor Satoka Kasai, who led the study, explained. “The mice showed high sensitivity without injury or direct pain stimulation, but were caused by exposure to sound pressure.”

Pain caused by brain inflammation drives sound

Analyzing brain tissue from DNA microarrays reveals the biological mechanism behind this phenomenon. Exposed sound pressure triggers significant changes in gene expression in the thalamus, a brain region where pain signals are performed before reaching conscious consciousness.

This analysis identified 444 upregulated genes and 231 downregulated genes, many of which were associated with inflammatory responses. Two genes showed particularly significant increases: prostaglandin-Nethinase synthase 2 (17.3-fold increase) and CXC motif chemokine ligand 1 (14.1-fold increase).

Key research results:

• Sound pressure alone lowers pain threshold for three days
• The cerebral inflammation gene increases dramatically after ultrasound exposure
• Anti-inflammatory drugs reverse sound-induced pain sensitivity
• Mice with existing inflammatory pain have recovered from distress calls for a long time
• Effects occur without visual, olfactory or touch contact

The therapeutic significance of chronic pain

Researchers tested whether anti-inflammatory drugs could counteract sound-induced hyperalgesia. Both Loxoprofen (COX-2 inhibitor) and SB225002 (chemokine receptor antagonist) significantly reduced pain response when administered after sound stress exposure.

Perhaps more worrying is that the recovery period is significantly prolonged when mice with inflammatory pain are exposed to distress calls. Although normal inflammatory pain is usually resolved within 14 days, the sensitivity of the sound pressure mice is prolonged for 21 days.

The effectiveness of pain relief medications is also impaired in animals with sound stress, suggesting that environmental noise may interfere with treatment outcomes in clinical settings.

Environmental stress and medical recovery

The implications of this study go beyond the real-world medical environment observed by the laboratory. Hospital sounds, including alarms, machinery and patient distress, may inadvertently worsen the pain and delay recovery through similar neuroinflammatory pathways.

“In addition to causing brain inflammation to cause hyperalgesia, sound stress can also aggravate inflammatory pain and may interfere with the treatment of pain,” said Dr. Kasai pointed out. “Our research can help improve understanding of stress-related pain and guide the development of scientifically-based pain management treatment strategies.”

The study involved carefully controlled conditions that allowed mice to hear only ultrasound frequencies above 20 kHholz – not clearly audible to humans, but within the hearing range of mice, frequencies up to 100 kHholz could be detected.

Although the study focuses on mice, the results suggest that auditory stress may affect pain in various species. The study highlights how social and environmental factors create real physiological changes that complicate pain management and recovery processes.

Future studies will examine whether specific sound frequencies or emotional contents of vocalization drive these effects, which may lead to acoustic interventions that may minimize harmful sound stress and may even promote healing in a medical setting.

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