Role of tear size and tendon degeneration for development of pain in rat models of rotator cuff tear

Toru Morimoto; Masashi Izumi; Koji Aso; Masahiko Ikeuchi

doi:10.1016/j.jse.2023.12.013

Role of tear size and tendon degeneration for development of pain in rat models of rotator cuff tear

J Shoulder Elbow Surg. 2024 Feb 3:S1058-2746(24)00079-X. doi: 10.1016/j.jse.2023.12.013. Online ahead of print.

Authors

Toru Morimoto¹, Masashi Izumi², Koji Aso¹, Masahiko Ikeuchi³

Affiliations

¹ Department of Orthopaedic Surgery, Kochi Medical School, Kochi University, Nankoku, Japan.
² Department of Orthopaedic Surgery, Kochi Medical School, Kochi University, Nankoku, Japan; Department of Rehabilitation, Kochi Medical School Hospital, Kochi University, Nankoku, Japan. Electronic address: izumim@kochi-u.ac.jp.
³ Department of Orthopaedic Surgery, Kochi Medical School, Kochi University, Nankoku, Japan; Department of Rehabilitation, Kochi Medical School Hospital, Kochi University, Nankoku, Japan.

PMID: 38311102
DOI: 10.1016/j.jse.2023.12.013

Abstract

Background: Rotator cuff tear (RCT) is a frequent etiology of shoulder pain and disability; however, the triggers for the onset and aggravation of pain remain obscure. In this study, we established novel rat RCT models to examine the impact of tear size and tendon degeneration on pain.

Methods: Fifty-five adult male Sprague-Dawley rats were allocated into 4 study groups: large tear (L group, n = 10), small tear (S group, n = 15), small tear with scratching (S+ group n = 15), and sham surgery (Sham group, n = 15). Pain-related behaviors were evaluated by weight distribution of forelimbs during a 5-minute free gait using a dynamic weight-bearing apparatus at 2, 4, 6, and 8 weeks. Calcitonin gene-related peptide (CGRP) expressions in ipsilateral dorsal root ganglion (DRG) neurons of C4, C5, and C6 were evaluated at 4 and 8 weeks. The area of scar tissues around the torn tendon, infiltration of inflammatory cells, and severity of tendon degeneration (modified Bonar score) were histologically assessed at 4 and 8 weeks. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to evaluate the levels of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) expression in torn tendons and surrounding tissues at 4 weeks.

Results: The weight distribution ratio (ipsilateral and contralateral side) was significantly decreased in the L and S+ group compared with its baseline and Sham group (P < .05), but the S group showed no significant difference compared with the Sham. The ratio of CGRP-immunoreactive neurons in the DRGs was significantly higher in the L and S+ groups than in the S and Sham groups. The histologic assessment indicated that scar tissue formation was more extensive in the L group than in the S and S+ groups. Still, there was no significant difference between the S and S+ groups. The modified Bonar score was considerably higher in the S+ group than in the S group. Furthermore, ELISA analysis demonstrated no significant disparity in COX-2 levels between the groups; however, NGF levels were substantially higher in the S+ group than in the S and Sham groups.

Conclusion: The present study provides compelling evidence that large RCT is strongly associated with heightened pain severity in a rat model. Nevertheless, even a small tear can significantly aggravate pain when the torn tendon is degenerated. CGRP upregulation driven by peripheral NGF possibly played a pivotal role in the genesis and exacerbation of pain in small RCT.

Keywords: Rotator cuff tear (RCT); calcitonin gene-related peptide (CGRP); nerve growth factor (NGF); pain; tendon degeneration.