Melatonin Plays a Role as a Mediator of Nocturnal Pain in Patients with Shoulder Disorders
- Author(s)
- Eunyoung Ha; Yun-Mee Lho; Hyuk-Jun Seo; Chul-Hyun Cho
- Keimyung Author(s)
- Ha, Eun Young; Cho, Chul Hyun
- Department
- Dept. of Biochemistry (생화학)
Dept. of Orthopedic Surgery (정형외과학)
- Journal Title
- Journal of bone and joint surgery. American Volume.
- Issued Date
- 2014
- Volume
- 96
- Issue
- 13
- 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-1b (IL-1b) and tumor
necrosis factor-a (TNF-a) significantly stimulated the expression of MTNR1A and MTNR1B in primary cultured fibroblastlike
synoviocytes treated with proinflammatory cytokines. Melatonin treatment at a physiological concentration (10 nM)
induced ASIC3 expression and IL-6 production. Treatment with luzindole, amelatonin-receptor antagonist, reversedmelatoninstimulated
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.
Clinical Relevance: Melatonin may be a therapeutic target of chronotherapy.
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