Therapeutic Effects and Mechanistic Insights of Low-Intensity Focused Ultrasound in Peripheral Neuropathic Pain.

OBJECTIVE: To investigate the therapeutic effects and underlying mechanisms of low-intensity focused ultrasound (LIFU) in peripheral neuropathic pain (NP). METHODS: Eight-week-old Sprague-Dawley rats were randomly assigned to four groups: Normal (no treatment), Sham (sciatic nerve exposure only), chronic constriction injury (CCI), and CCI + LIFU (LIFU applied after injury). Behavioral tests were conducted 7-9 days post-intervention. Rats were then anesthetized and sacrificed for dorsal root ganglion (DRG) collection. RNA sequencing (RNA-seq) was performed to identify differentially expressed genes. Enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to assess inflammatory cytokines. Electrophysiological changes were evaluated using electromyography and patch-clamp techniques at both nerve fiber and cellular levels. RESULTS: Compared with the CCI group, rats in the CCI + LIFU group showed significantly increased mechanical and thermal pain thresholds (n = 7, P < 0.05), with no difference between Sham and Normal groups. Electrophysiological analysis indicated reduced nerve fiber excitability and suppressed inward sodium currents following LIFU treatment (n = 5, P < 0.05). RNA-seq demonstrated downregulation of inflammation-related genes in the CCI + LIFU group. Consistently, ELISA and immunofluorescence revealed significantly decreased expression of tumor necrosis factor-α, interleukin-1β, and calcitonin gene-related peptide compared with the CCI group. CONCLUSION: LIFU can alleviate peripheral NP by inhibiting the transmission of pain signals from peripheral injury sites to the DRG, thereby achieving sustained blockade of nociceptive signaling and effectively reducing peripheral sensitization.