# Focused Ultrasound in the Rehabilitation Setting:
## 4 Discussion and Future Directions
### Musculoskeletal Disabilities  
FUS has also been applied in the treatment of MSK conditions, such as refractory knee pain and facet joint pain, conditions that often lead to functional disability and impair QOL. While several treatment options exist for knee osteoarthritis [49; 50; 51] and facet joint pain [52; 53], surgery remains the only option in certain cases. However, surgery is often not feasible due to patient unwillingness or poor health conditions. Furthermore, surgical interventions carry a higher risk of severe complications compared to conservative treatments, with chronic postsurgical pain reported in 10-34% of cases [54]. This underscores the need for advanced, minimally invasive, nonsurgical interventions to manage MSK conditions effectively. MRgFUS has garnered attention for its precision, noninvasive real-time monitoring capabilities, and potential to reduce pain sensitization. [PERSON] et al. demonstrated that MRgFUS not only effectively managed refractory pain but also improved physical function without adverse events in elderly patients with medial knee osteoarthritis. Similarly, [PERSON] et al. reported positive outcomes using MRgFUS for lumbar facet joint ablation, highlighting its promise as a therapy for facet joint-mediated low back pain. The mechanism of MRgFUS in MSK conditions appears to involve localized degeneration of nociceptors and nerve fibers through thermal denaturation of peri-articular tissues in the medial femortibial joint. Heating these tissues beyond the protein denaturation threshold (55 \({}^{\circ}\)C) results in localized denervation [55]. MRgFUS offers several advantages for treating MSK conditions, including noninvasive thermal ablation without the need for ionizing radiation or needles, the ability to treat multiple joints in a single session, and the option to repeat treatments if symptoms recur. MRI guidance provides direct visualization of treatment targets and real-time monitoring with MRI thermometry, ensuring precise targeting. However, challenges include the complex etiology of MSK conditions, which requires careful patient selection, and contraindications to MRI. Clinicians must accurately identify treatment targets and ensure the safety of the beam path to avoid unintended tissue damage. Considering their ability to reduce pain, FUS has shown potential in addressing pain associated with limb amputation and neuropathic conditions. Despite advancements like targeted muscle reinnervation, which connects transected nerves to neuromuscular junctions to reduce neurom-related pain, many patients still suffer from pain due to peripheral and central mechanisms [56; 57]. FUS could be applied to stimulate peripheral nerves at or near the distal tips of transected nerves, potentially activating dormant thalamus-cortex circuits to restore motor and sensory functions, as hypothesized by [PERSON] et al. Preclinical studies, such as those by [PERSON] et al., support this concept by demonstrating FUS's ability to activate dormant neural pathways, including transcranial ultrasound stimulation of the thalamus [58]. If validated, this approach could revolutionize rehabilitation by reducing pain and improving functionality in individuals with nerve injuries or amputations. FUS also offers promise for cancer-related neuropathic pain, which affects up to 40% of cancer survivors [59]. This pain arises from direct neural damage caused by tumors or treatments like chemotherapy. Current options often involve significant side effects, emphasizing the need for safer alternatives [60]. FUS provides a noninvasive technique that avoids surgery and invasive procedures, reducing infection risks and recovery times. It precisely targets specific nerves or tissues without harming surrounding areas, directly stimulating peripheral and central nervous systems to promote functional activity in damaged tissues.