Objective <p>To observe the effects of shoulder-three-needle therapy plus joint mobilization and extracorporeal shock wave therapy (ESWT) in improving symptoms and pain mediators in patients with scapulohumeral periarthritis.</p> Methods <p>A total of 82 patients with scapulohumeral periarthritis were randomized into a control group and an observation group by the random number table method, with 41 cases in each group. The control group was treated with ESWT. The observation group was treated with additional shoulder-three-needle therapy plus joint mobilization based on the treatment in the control group. After 4 weeks of treatment, shoulder joint function, pain mediators, inflammatory factor levels, and clinical efficacy were compared between the two groups.</p> Results <p>The total clinical effective rate and the score of shoulder joint function in the observation group were higher than those in the control group (<i>P</i>&lt;0.05). After treatment, the levels of serum pain mediators substance P (SP), 5-hydroxytryptamine (5-HT), and prostaglandin E₂ (PGE₂), as well as inflammatory factors interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) decreased significantly in both groups (<i>P</i>&lt;0.05). And, the serum pain mediators SP, 5-HT, and PGE₂ and the levels of inflammatory factors IL-6, TNF-α, and CRP in the observation group were all lower than those in the control group (<i>P</i>&lt;0.05).</p> Conclusion <p>Shoulder-three-needle therapy plus joint mobilization and ESWT has a better curative effect than ESWT alone in treating scapulohumeral periarthritis. it can effectively improve the clinical symptoms, reduce the levels of pain mediators and inflammatory factors, and increase shoulder joint function.</p>