Background <p>Neuropathic pain is a complex condition that can be challenging to manage, despite the availability of a variety of pharmacologic and non-pharmacologic treatment approaches. This narrative review aimed to synthesize preclinical evidence on the therapeutic effects and underlying mechanisms of focused ultrasound (FUS) in neuropathic pain models.</p> Methods <p>We conducted a narrative literature search using PubMed to identify preclinical studies investigating the use of FUS in the context of neuropathic pain. Studies were retrieved from PubMed using keyword combinations “focused ultrasound” and “neuropathic pain,” with no restrictions on country of origin. Studies published in English from inception to December 2024 were considered. Eligible studies were limited to those involving animal models or in vitro cell models relevant to neuropathic pain. Clinical studies, review articles, editorials, and studies unrelated to neuropathic mechanisms were excluded.</p> Results <p>A total of 28 preclinical studies were identified, all employing either animal or cell-based models of neuropathic pain. Across various nerve injury models, both high-intensity (HIFU) and low-intensity focused ultrasound (LIFU) were associated with behavioral improvements indicative of pain reduction, partial restoration of nerve function, and modulation of inflammatory cytokine profiles. Although the precise mechanisms remain to be fully elucidated, current evidence suggests that FUS may exert its effects through thermal, mechanical, and neuromodulatory pathways, including modulation of inhibitory neurotransmission, suppression of neuroinflammation, and regulation of ionic homeostasis.</p> Conclusions <p>Preclinical studies indicate that FUS may alleviate neuropathic pain via thermal, mechanical, and neuromodulatory mechanisms. However, clinical translation remains uncertain, highlighting the need for further investigation in human models.</p>