Pain and gain-an evaluation of the role of cytokines in rotator cuff healing

There is evidence that patients who experience more pain and restricted motion prior to and/or after arthroscopic rotator cuff repair are more likely to heal their repairs. The mechanisms underlying this "pain and gain" phenomenon are undetermined. The aim of this study was to determine if the signaling molecules interleukin (IL)-6, IL-1&#x3b2;, and IL-8, which are involved in tendon healing, were associated with this "pain and gain" process postrotator cuff repair. Tendon samples from 19 consecutive patients were collected intraoperatively from the torn edge of the supraspinatus tendon closest to the biceps tendon during arthroscopic rotator cuff repair. IL-6, IL-1&#x3b2;, and IL-8 cytokine staining in the tendon samples were evaluated using immunohistochemistry and quantified with QuPath software. Patient outcomes were assessed preoperatively and at 6-week, 12-week, and 24-week follow-ups. Tendon repair integrity was assessed with ultrasound. The stiffness (kPa) of the healing supraspinatus tendon preoperatively and at 6-week, 12-week, and 24-week follow-ups was quantified with shear wave elastography using an ACUSON S3000 ultrasound system (Siemens, California, USA) with a Linear 9L4 transducer. The torn tendon edges of patients with restricted preoperative range of motion (<120&#xb0; forward flexion or <30&#xb0; external rotation) had 1.4-fold increased expression of IL-1&#x3b2; (P = .03) and IL-6 (P = .01) positive cells compared to patients without range of motion restriction. Patients with increased IL-6, IL-1&#x3b2;, and IL-8 expression measured in the intraoperative tendon were also more likely to have increased patient-rated pain scores both preoperatively and at 6-, 12-, and 24-week follow-up. Patients who had torn tendons with increased IL-1&#x3b2; (r = 0.58, P = .02) and IL-8 (r = 0.69, P = .01) expression had higher tendon elastography values at 6 weeks postrotator cuff repair. This data support the hypothesis that increased expression of IL-6, IL-1&#x3b2;, and IL-8 at the edge of the torn supraspinatus tendon is associated with a stronger healing response and stiffer, more robust tendons postrepair. Elevated cytokine levels in the intraoperative torn tendon were associated with increased pain and restricted passive range of motion and with improved tendon mechanical strength as indicated by higher elastography values in the healing tendon. In other words, IL-6, IL-1&#x3b2;, and IL-8 are key players in the "pain and gain" phenomenon following rotator cuff repair.