Melatonin Plays a Role as a Mediator of Nocturnal Pain in Patients with Shoulder Disorders.

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.

CLINICAL RELEVANCE: Melatonin may be a therapeutic target of chronotherapy.