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

Background/Objectives: 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. Methods: 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. Results: 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 (p = 0.0022), S1 (p = 0.0150), S2 (p = 0.0055), and all other branches combined (p < 0.001; w = 0.58, large effect). S2 also demonstrated greater sensitivity than L5 (p = 0.003) and S1 (p = 0.001). Subdivision analysis revealed uniformly high sensitivity across S3, whereas S1 and S2 displayed heterogeneous patterns. Conclusions: 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.