Integrated Low Intensity Ultrasound–Magnetic Neuromodulation Produces Sustained Analgesia in a Rodent Neuropathy Model

Background: Chronic neuropathic pain is difficult to manage, as many treatments are invasive, opioid-dependent, or provide limited relief. Noninvasive neuromodulation approaches such as low-intensity focused ultrasound (LIFU) and trans-spinal magnetic stimulation (TSMS) show promise but are individually constrained in their ability to effectively target spinal pain circuits.Objective: This study evaluates a novel multimodal neuromodulation platform that delivers simultaneous LIFU and TSMS (LIFU/TSMS) and assesses its safety and analgesic efficacy in a rat model of peripheral neuropathic pain.Methods: Adult male and female Sprague Dawley rats underwent common peroneal nerve injury. Seven days post-injury, animals received either a single 45-minute LIFU/TSMS targeting the T13/L1 or sham stimulation. Mechanical and thermal allodynia were assessed using von Frey and hot plate tests, respectively, along with evaluations of locomotor activity and depression-like behavior. Postmortem spinal histology evaluated tissue integrity and neuronal degeneration.Results: LIFU/TSMS significantly reduced mechanical allodynia within 1 hour in both females (p = 0.02) and males (p = 0.004) compared with sham. Mechanical analgesia persisted for up to 7 days in females (p = 0.003 at day 7) and up to 5 days in males (p = 0.04). Thermal hypersensitivity was reduced at 24 hours in both sexes (females p = 0.012; males p < 0.001), with a larger effect in males. No spinal tissue injury or neuronal degeneration was observed.Conclusion: LIFU/TSMS produces rapid and durable analgesia in a rodent model of neuropathic pain without detectable tissue damage, supporting multimodal spinal neuromodulation as a promising therapeutic strategy.