# Melatonin administration attenuates fibrosis progression in frozen shoulder syndrome: a rat model study

## TL;DR

Melatonin may help reduce fibrosis in frozen shoulder syndrome, based on a rat model study showing improved joint pathology.

## Contribution

This study demonstrates melatonin's anti-fibrotic effects in a rat model of frozen shoulder syndrome.

## Key findings

- Melatonin significantly attenuated fibrosis progression in the shoulder joint.
- Synovial hypertrophy decreased over time in some groups, but no significant differences were observed in inflammation or hypervascularity.
- Fibrosis levels were significantly lower in the melatonin group at 8 weeks compared to the antagonist group.

## Abstract

Frozen shoulder syndrome, or adhesive capsulitis, is characterized by pain and restricted joint mobility due to fibrotic changes within the shoulder joint capsule. Despite its potential for spontaneous resolution, persistent symptoms often necessitate further treatment. Melatonin, known for its anti-inflammatory and anti-fibrotic properties, has emerged as a promising therapeutic agent for this condition. This study aimed to investigate the impact of melatonin on adhesive capsulitis in a rat model, focusing on its potential to attenuate fibrosis progression and improve joint pathology.

Thirty female Sprague-Dawley rats were utilized in this study. Frozen shoulder syndrome was surgically induced, and the rats were divided into three groups: G1 receiving a melatonin antagonist, G2 receiving daily melatonin supplementation, and G3 without intervention. Histopathological evaluations were conducted at weeks 8 and 16 post-simulation to assess fibrosis, synovial hypertrophy, inflammatory cell infiltration, and hypervascularity. Statistical analyses were performed to determine significant differences between the groups.

Histological evaluations revealed that melatonin administration significantly attenuated fibrosis progression in the shoulder joint, particularly in the G2 (p < 0.05). No significant differences were observed in synovial hypertrophy, inflammatory cell infiltration, or hypervascularity between the groups (p > 0.05). Survival rates indicated no fatalities in the group receiving daily melatonin supplementation. Statistical analysis showed significant differences in fibrosis levels at 8 weeks between groups, with G1 exhibiting higher rate of severe fibrosis (p = 0.038). However, at 16 weeks, no significant differences were observed between groups (p > 0.05). Temporal changes within groups indicated a significant decrease in fibrosis levels and synovial hypertrophy from 8 to 16 weeks in G1 and G3 (p < 0.05). A comparison between operated and non-operated sides revealed significant differences in fibrosis levels in both groups at 8 and 16 weeks (p < 0.05).

Melatonin administration demonstrated potential therapeutic benefits in attenuating fibrosis progression and reducing synovial hypertrophy in adhesive capsulitis.

NA, Animal Study

The online version contains supplementary material available at 10.1186/s12891-025-09198-3.