title: Melatonin Plays a Role as a Mediator of Nocturnal Pain in Patients with Shoulder Disorders.
abstract: BACKGROUND
  Nocturnal pain is commonly observed in patients with shoulder disorders such as a rotator cuff tear or frozen shoulder. This study was conducted to explore the possibility that melatonin plays a role as a mediator of nocturnal pain in patients with a rotator cuff tear or frozen shoulder.
  
  
  METHODS
  Subacromial bursa and joint capsule samples were collected from sixty-three patients: twenty-one patients with a rotator cuff tear, twenty-two with frozen shoulder, and twenty with shoulder instability (control group). The expression of melatonin receptor 1A (MTNR1A) and 1B (MTNR1B) and of acid-sensing ion channel 3 (ASIC3) in the subacromial bursa and the joint capsule were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. The protein level of ASIC3 was measured by immunoblot analysis. To determine the effect of melatonin as a pain mediator, an in vitro study with use of primary cultured fibroblast-like synoviocytes was performed by semiquantitative RT-PCR analysis, immunoblot analysis, and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  MTNR1A, MTNR1B, and ASIC3 expression was significantly increased in both the rotator cuff tear and frozen shoulder groups compared with the control group of patients with shoulder instability. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) significantly stimulated the expression of MTNR1A and MTNR1B in primary cultured fibroblast-like synoviocytes treated with proinflammatory cytokines. Melatonin treatment at a physiological concentration (10 nM) induced ASIC3 expression and IL-6 production. Treatment with luzindole, a melatonin-receptor antagonist, reversed melatonin-stimulated ASIC3 expression and IL-6 production.
  
  
  CONCLUSIONS
  Our study suggests that melatonin may play a role as a mediator of nocturnal pain with a rotator cuff tear or frozen shoulder, and this effect may be mediated via melatonin receptors.
  
  
  CONCLUSIONS
  Melatonin may be a therapeutic target of chronotherapy.
authors.affiliation: Departments of Biochemistry (E.H. and Y.-M. L.) and Orthopedic Surgery (H.-J. S. and C.-H.C.), Dongsan Medical Center, School of Medicine, Keimyung University, 56 Dalseong-ro, Jung-gu, Daegu 700-712, Republic of Korea. E-mail address for C.-H. Cho: oscho5362@dsmc.or.kr.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ha
authors.affiliation: Departments of Biochemistry (E.H. and Y.-M. L.) and Orthopedic Surgery (H.-J. S. and C.-H.C.), Dongsan Medical Center, School of Medicine, Keimyung University, 56 Dalseong-ro, Jung-gu, Daegu 700-712, Republic of Korea. E-mail address for C.-H. Cho: oscho5362@dsmc.or.kr.
authors.forename: Yun-Mee
authors.initials: YM
authors.lastname: Lho
authors.affiliation: Departments of Biochemistry (E.H. and Y.-M. L.) and Orthopedic Surgery (H.-J. S. and C.-H.C.), Dongsan Medical Center, School of Medicine, Keimyung University, 56 Dalseong-ro, Jung-gu, Daegu 700-712, Republic of Korea. E-mail address for C.-H. Cho: oscho5362@dsmc.or.kr.
authors.forename: Hyuk-Jun
authors.initials: HJ
authors.lastname: Seo
authors.affiliation: Departments of Biochemistry (E.H. and Y.-M. L.) and Orthopedic Surgery (H.-J. S. and C.-H.C.), Dongsan Medical Center, School of Medicine, Keimyung University, 56 Dalseong-ro, Jung-gu, Daegu 700-712, Republic of Korea. E-mail address for C.-H. Cho: oscho5362@dsmc.or.kr.
authors.forename: Chul-Hyun
authors.initials: CH
authors.lastname: Cho
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002062:Bursitis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D007593:Joint Instability / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000070636:Rotator Cuff Injuries / Q000378:metabolism*; D012785:Shoulder Joint / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D015415:Biomarkers; C000610981:MTNR1A protein, human; C573871:MTNR1B protein, human; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin