Low-Intensity Pulsed Ultrasound Ameliorates Neuropathic Pain Induced by Partial Sciatic Nerve Ligation Via Regulating Macrophage Polarization

Inflammatory (M1-polarized) macrophages cause neuropathic pain (NP) after nerve injury through non-resolving neuroinflammation. However, increasing evidence suggests that converting M1 to anti-inflammatory M2 macrophages may rescue NP. In the present study, the therapeutic potential of low-intensity pulsed ultrasound (LIPUS) was investigated in a partial sciatic nerve ligation (PSL)-induced NP model. Materials and Methods: Abnormal pain sensation, such as tactile allodynia, was caused by PSL. Immediately after PSL induction, the mice were subjected to LIPUS treatment for 20 min/day for 7 days. LIPUS was used at an average intensity of 60 mW/cm2 and a frequency of 1.5 MHz. Results: In the behavioral test, the LIPUS group showed a significant improvement in the PSL-induced hypersensitivity compared to the PSL group not exposed to LIPUS. We found an increasing number of M2 macrophages in the injured sciatic nerves after LIPUS exposure. LIPUS treatment decreased expression of pro-inflammatory microglial markers in spinal cord. Conclusions: Our data suggest that LIPUS has an anti-nociceptive effect by increasing anti-inflammatory M2 macrophage and may be a suitable therapeutic candidate for NP.