Acoustic Motor Cortex Stimulation Enhances the Descending Analgesic Pathway to Alleviate Chronic Pain in Mice
Weiliang Fu, Guanghua Yang, Jin Ke, Tianwen Huang, Jinpeng Li, Xiaoyan Chen, Junjie Zou, Zhengrong Lin, Lili Niu, Yongjie Li
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2025 · 10.1109/tnsre.2025.3564033
Abstract
Chronic pain poses considerable health risks, necessitating the development of effective treatments. Physical modulation of the motor cortex has demonstrated promise for pain relief; however, existing methods require invasive electrode implantation or have limited spatial resolution. Therefore, we developed a non-invasive, high-precision acoustic motor cortex stimulation (aMCS) system to alleviate chronic pain and explore its mechanisms. We developed a wearable aMCS system and employed the spared nerve injury (SNI) method to establish a mouse model of chronic pain. The model mice underwent aMCS with different acoustic parameters, and their pain behaviors were systematically evaluated. Subsequently, we established a long-term spinal cord two-photon system to monitor the effects of aMCS on spinal cord dorsal horn (SCDH) neuronal activity. Next, TRAP2-tdTomato mice were used to examine the effects of aMCS on the motor cortex and other regions of the descending analgesic pathway. Finally, we conducted magnetic resonance imaging, histology, and temperature monitoring to evaluate the safety of aMCS. aMCS with specific parameters significantly ameliorated pain behaviors in a mouse model of chronic pain. Two-photon calcium imaging indicated that aMCS reduced the intensity of neuronal activity in SCDH. Activity mapping in TRAP2-tdTomato mice revealed that aMCS enhanced neuronal activity in the primary motor cortex and zona incerta while diminishing it in the lateral periaqueductal gray and SCDH. Safety assessments confirmed the absence of deleterious effects on the stimulated region. aMCS provides a novel, non-invasive and effective approach to alleviating chronic pain by potentially enhancing the descending analgesic pathway.
Abstract via pubmed.
Exposures
Exposure 1: acoustic motor cortex stimulation (aMCS), Groups 1-4 parameter sweep
Target: primary motor cortex — “M1 (primary motor cortex)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 4,170 | ✓✓✓ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | 100, 100, 5, 50swept | ✓✓✓⚑ |
| Duty cycle (%) | 10 | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 1,100, 225, 1,100, 1,100swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 870, 179, 870, 870swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Four parameter groups (paired PRF/pressure combinations, in order Group1-4) shared sonication duration (SD)=1 s, inter-stimulus interval (ISI)=10 s, and duty cycle (DC)=10%. Mice received one week of daily 15-minute aMCS sessions starting on the 8th day post-SNI surgery; sham/control animals had the transducer mounted identically but received no ultrasound energy. Separate cohorts received Group 1 parameters for two-photon spinal calcium imaging (1 week of aMCS), TRAP2 activity mapping (2 consecutive days of 15 min aMCS), and safety assessment.
Flags from extraction
n_subjects— Paper never states one overall total of aMCS-exposed mice (95 total mice includes sham/control/excluded animals); listed the per-cohort group sizes that received real aMCS (behaviour Groups 1-4: n=8,7,6,7; SCDH calcium-imaging cohort: n=3; TRAP2 cohort: n=4; safety cohort: n=3) rather than summing them.exposures[0].timing.pulse_duration_ms— Only PRF (100/5/50 Hz) and duty cycle (10%) are stated; pulse duration is not independently reported and was not computed from duty_cycle/PRF per the rule against deriving this value.exposures[0].timing.pulse_repetition_frequency_hz— PRF and acoustic pressure vary together across four named groups (paired combinations, not a full factorial); recorded as parallel lists in Group1-4 order rather than independent sweeps.n_sessions_per_subject— Session count differs by sub-experiment: ~7 daily sessions (1 week) for the main behaviour and SCDH-imaging cohorts, 2 sessions for the TRAP2 cohort, and an unspecified number for the safety cohort; no single figure applies to the whole study.exposures[0].device— Transducer described only as custom-built (12 mm radius of curvature, 4.17 MHz); no manufacturer or model name given for the transducer itself (only for the function generator and amplifier).