Nerve growth factor continuously elevates in a rat rotator cuff tear model

• Published in: Journal of shoulder and elbow surgery 2019-01, Vol.28 (1), p.143-148
• Main Authors: Nagura, Naoshige, Kenmoku, Tomonori, Uchida, Kentaro, Nakawaki, Mitsufumi, Inoue, Gen, Takaso, Masashi
• Format: Article
• Language: English
• Subjects: Animals; COX-2; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; interleukin (IL)-1β; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Models, Animal; nerve growth factor; Nerve Growth Factor - genetics; Nerve Growth Factor - metabolism; pain; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Rotator Cuff - metabolism; Rotator Cuff Injuries - metabolism; Rotator cuff tear; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor-α
• ISSN: 1058-2746; 1532-6500
• DOI: 10.1016/j.jse.2018.06.030

Nerve growth factor (NGF) plays a key role in osteoarthritic pain and low back pain. Rotator cuff tear (RCT) is often associated with severe shoulder pain. However, the role of NGF in RCT remains to be fully understood. Rats were divided into sham and RCT groups. The rotator cuff was harvested from the sham and RCT groups on various days for reverse transcription-polymerase chain reaction analysis of Tnfa, Ngf, Il1b, and Cox2 expression. Rotator cuffs from the sham and RCT groups were also harvested at 1 and 14 days for enzyme-linked immunosorbent assay and immunohistochemistry to assess NGF protein levels and localization. Rotator cuff–derived cells were stimulated with rat recombinant tumor necrosis factor (TNF)-α to investigate the involvement of TNF-α in the regulation of NGF expression. Tnfa and Ngf messenger RNA levels increased within 1 day in the RCT group. Notably, Tnfa and Ngf upregulation persisted for up to 56 days after the RCT surgery, while Il1b and Cox2 expression was significantly reduced. NGF levels in the RCT group were significantly higher than those in the sham operation group on days 1 and 14. Certain inflammatory cells and synovial-like cells lining the surface of the laminated tears were NGF-positive on days 1 and 14, respectively. Ngf messenger RNA levels increased significantly in rotator cuff–derived cells after TNF-α stimulation. NGF levels are continuously elevated in RCT, which is mainly regulated by TNF-α. NGF may thus represent a potential target for therapies that modulate RCT pain.