Oral colchicine, a cheap and decades-old gout drug, has shown for the first time that it can loosen the stiffened shoulders of rats with experimentally induced frozen shoulder while simultaneously dampening both the inflammation and the fibrosis that drive the condition. In a carefully controlled animal study, treated rats regained significantly more shoulder motion than untreated controls, and microscopic examination of their joint capsules revealed less scar-like tissue deposition and fewer signs of inflammation. The findings, published in Experimental Biology and Medicine, point to a treatment strategy that goes beyond the anti-inflammatory drugs currently used in humans, which leave the fibrotic component of the disease untouched.
Frozen shoulder, known medically as adhesive capsulitis, is a painful condition in which the shoulder becomes progressively stiffer, with both active and passive movement restricted. It typically arises spontaneously, without an obvious trigger, and follows a long course through overlapping inflammatory, fibrotic, and resolution phases. Inside the joint, synovial inflammation gives way to proliferation of fibroblasts and myofibroblasts, new vessel formation, and dense collagen deposition that thickens and contracts the glenohumeral capsule. Current conservative treatments, including nonsteroidal anti-inflammatory drugs and short courses of oral corticosteroids, target the inflammatory component but do not act directly on the capsular fibrosis that underlies lasting loss of motion. An agent that could suppress both processes at once would address a genuine unmet need.
Colchicine is a plant-derived alkaloid that has been used for more than fifty years against gout, familial Mediterranean fever, Behçet disease, and several fibrotic conditions. It binds to tubulin and inhibits microtubule polymerization, which suppresses neutrophil chemotaxis and inflammasome-driven cytokine release while also interfering with fibroblast proliferation and collagen secretion. These actions map directly onto the two processes thought to sustain frozen shoulder. Colchicine also reduces adhesion formation in several experimental models, including pelvic adhesions in rabbits and peritoneal adhesions in rats. Despite this rationale, its effect on the inflammatory and fibrotic changes of frozen shoulder had not previously been studied.
To test the hypothesis, researchers at Bursa UludaÄŸ University in Türkiye induced frozen shoulder in sixty female Wistar albino rats aged eight months by immobilizing the left forelimb in a plaster cast with the shoulder held in full adduction and internal rotation. The animals were randomly assigned to five groups of twelve: a healthy sham group, an untreated three-week control, a three-week treatment group, an untreated six-week control, and a six-week treatment group. Rats in the treatment arms received 0.6 milligrams of colchicine daily by gavage, a dose corresponding to roughly 2.2 milligrams per kilogram of body weight. In the early-treatment group, dosing began on the third day after casting, when inflammation was expected to dominate; in the late-treatment group, it began at three weeks, when mature fibrosis had already developed. The researchers deliberately timed the two arms to probe the drug’s anti-inflammatory and antifibrotic properties separately.
Shoulder motion was assessed ex vivo on harvested specimens rather than in living animals. Using a standardized jig and a fixed ten-gram torque applied to the humeral shaft, blinded investigators measured abduction and external rotation angles radiographically. This approach reflects passive capsular stiffness rather than active, functional shoulder movement, but it removes the confounding effects of daily loading and provides reproducible measurements. At six weeks, the mean abduction angle was 109.6 degrees in the treated group compared with 88.1 degrees in the untreated control, a statistically significant improvement of 21.5 degrees. External rotation also improved, rising from 18.9 degrees to 26.8 degrees. In the three-week groups, abduction angles did not differ significantly between treated and untreated animals, suggesting the functional benefit emerges as fibrosis progresses rather than during the earliest inflammatory stage.
Histopathological analysis of the joint capsules told a matching story. Connective tissue formation was significantly lower in both treatment groups than in their respective controls, and inflammatory changes were reduced at both time points. Immunohistochemical staining for collagen types revealed a phase-dependent pattern: collagen III, the immature fibrillar collagen that predominates early in scar formation, was lower in the three-week treatment group than in its control, while collagen I, the mature collagen that accumulates as fibrosis matures, was lower in the six-week treatment group. In other words, colchicine lowered whichever collagen type was predominant during the period in which it was administered. Differences in synovial hyperplasia, pannus formation, and capillary vessel formation did not reach statistical significance, indicating that the anti-angiogenic and anti-proliferative effects were less consistent than the antifibrotic and anti-inflammatory ones.
The study’s authors are careful to distinguish between preventing fibrosis and reversing it. In the early-treatment arm, colchicine was started before mature fibrosis had developed, so the effect there is one of prevention. In the late-treatment arm, treatment began when fibrosis was already present, but immobilization was maintained until the animals were euthanized, meaning the comparison measures attenuation of continuing fibrosis under a continuing stimulus rather than resolution after the stimulus has been removed. Neither arm tested whether colchicine can reverse established capsular contracture, which is the setting in which human patients usually present. The researchers note that testing this would require a model in which immobilization is discontinued once fibrosis has developed, treatment is then started, and motion is compared with that of untreated animals allowed to remodel spontaneously.
Several further caveats temper the findings. The sample size was modest, with six animals contributing to each endpoint, and the confidence intervals around many of the effect estimates are wide, several of them compatible with no difference. The abduction gain at six weeks is the only effect estimated with reasonable precision. The study used a single species and a single sex, and the rat shoulder differs from the human shoulder in loading, arc of motion, and the distribution of movement loss, with abduction most affected in rats and external rotation most affected in humans. The model also produces contracture through external immobilization rather than through the spontaneous synovial inflammation that defines primary frozen shoulder. Colchicine is cleared faster in rats than in humans, so the weight-normalized dose used here is not equivalent to a therapeutic human dose, and serum drug concentrations were not measured. Tolerability was assessed by daily clinical inspection alone, and body weight was not monitored serially during treatment, although no diarrhea, gastrointestinal signs, or gavage-related complications were observed and all sixty animals completed the study.
The study also lacked an active comparator, so the effects cannot be weighed against those of a short course of corticosteroids, an established treatment for frozen shoulder. A head-to-head comparison of colchicine and corticosteroids in the same rat model is planned, incorporating instrumented torque-angle measurement to capture joint stiffness across the full range of motion rather than at a single end-range angle. Upstream profibrotic mediators such as TGF-β1, α-SMA, and CTGF were not measured, meaning the data demonstrate reduced collagen deposition without establishing inhibition of a specific profibrotic pathway. The collagen findings rest on two planned comparisons in six animals per group and should be regarded as preliminary.
Taken together, the results position colchicine as a hypothesis-generating candidate rather than a proven therapy. The drug is inexpensive, orally available, and has a well-characterized safety profile in humans from decades of rheumatologic use, but it also has a narrow therapeutic index and clinically important drug interactions. The authors conclude that the present data support further preclinical evaluation rather than clinical use, and that adequately powered preclinical studies and, ultimately, clinical trials are needed before colchicine could be recommended for frozen shoulder. Any such trial would address established adhesive capsulitis, a setting this study did not model. What the work does establish is that targeting capsular fibrosis directly, rather than inflammation alone, is a viable strategy in a controlled animal system, and that a single old drug can act on both fronts at once.
Subject of Research: Testing oral colchicine against inflammation and fibrosis in a rat model of frozen shoulder
Article Title: Oral colchicine improves shoulder motion and reduces capsular fibrosis in a rat frozen shoulder model
Article References: Eken, G., Kantarci, A., Atici, T., Akkoc, A., & Akesen, S. (2026). Oral colchicine improves shoulder motion and reduces capsular fibrosis in a rat frozen shoulder model. Experimental Biology and Medicine, 251, Article 11233. https://doi.org/10.3389/ebm.2026.11233
Image Credits: AI Generated
Keywords: frozen shoulder, adhesive capsulitis, colchicine, rat model, capsular fibrosis, collagen, joint stiffness, preclinical study, anti-inflammatory, antifibrotic, immobilization, shoulder motion
News Source: Ophelia Keating. (October 28, 2026). Oral colchicine eases stiff shoulders and curbs scarring in rats with frozen shoulder. Scienmag.
