Identifying S3 and S2 as Key Pain-Sensitive Targets in High-Frequency Ultrasound Therapy for Sacroiliitis

<b>Background/Objectives:</b> Sacroiliitis is a painful inflammatory disorder of the sacroiliac joint, estimated to account for up to 25% of chronic low back pain. Treatment options are often limited, and many patients continue to experience symptoms despite conservative or interventional management. High-Intensity Focused ultrasound (HIFU) has emerged as a novel noninvasive neuromodulation technique. However, the contribution of individual lumbosacral nerve branches (L5-S3) to pain generation during such interventions remains unclear. This study aimed to characterize the distribution of pain-related interruptions during HIFU procedures, with a particular focus on identifying the most pain-sensitive targets. <b>Methods:</b> Eight patients with clinically confirmed sacroiliitis underwent HIFU ablation targeting the L5-S3 branches. Procedural data, including the total number of sonications and interruptions due to pain, were prospectively recorded. Statistical analyses were performed using chi-square tests, including overall distribution testing, pairwise branch comparisons, and an aggregated comparison of S3 versus all other branches combined. Effect sizes were calculated using Cohen's w. <b>Results:</b> Across 243 sonications, 162 interruptions (66.7%) occurred due to pain. Interruptions were unevenly distributed: 81% occurred at S2 and S3, with S3 alone accounting for 42%. S3 showed significantly more interruptions than L5 (<i>p</i> = 0.0022), S1 (<i>p</i> = 0.0150), S2 (<i>p</i> = 0.0055), and all other branches combined (<i>p</i> < 0.001; w = 0.58, large effect). S2 also demonstrated greater sensitivity than L5 (<i>p</i> = 0.003) and S1 (<i>p</i> = 0.001). Subdivision analysis revealed uniformly high sensitivity across S3, whereas S1 and S2 displayed heterogeneous patterns. <b>Conclusions:</b> HIFU stimulation revealed disproportionate pain sensitivity in sacral branches, with S3-and to a lesser extent S2-emerging as dominant contributors. These findings provide new insight into sacroiliitis pathophysiology and suggest prioritization of S3 in targeted interventional management.