What Are The Real Frozen Shoulder Causes?

Dr. Duplay first described frozen shoulder in the late 1800s and suggested that the underlying cause of the condition was soft tissue damage due to some kind of trauma. In the years since Dr. Duplay’s observations, research has shed new light on this condition and we now know that frozen shoulder is caused by inflammation and results in the formation of scar tissue in the shoulder joint. It is this scar tissue that ultimately makes movement difficult.

Prevailing Theories & New Possibilities

The underlying causes of the inflammation and the resolution of this process in frozen shoulder are still under investigation, though we have some indications of what might be happening in the tissues and cells that surround the joint. In this article, we will cover some of the more prevalent theories of frozen shoulder and we will examine some recently proposed, new theories of frozen shoulder causes.

Inflammation: what is it and how does it get started?

Inflammation is an essential immune response that can occur in every tissue in the body. The inflammatory response is characterized by redness, swelling and pain. There are many different types of inflammation but the underlying process is similar in almost every case. The process begins when something triggers the release of pro-inflammatory mediators. The quintessential pro-inflammatory mediator often involved in many types of inflammation is tumor necrosis factor alpha (TNFα) which works like a chemical communication system. TNFα signals the nearby cells to become inflamed and when these cells are inflamed they sometimes change shape, begin producing fibrotic factors that re-enforce the intercellular matrix and then they also begin secreting other activation signals. This causes changes in the cells that line the walls of the blood vessels, eventually leading to the expression of adhesion molecules that allow specialized immune cells (or inflammatory immune cells) to stick to them and pass into the tissues.

Once through the walls of the blood vessels, inflammatory immune cells migrate to the area of inflammation in response to signals from the local tissue cells. The cells that line the wall of the blood vessels also change and become more permeable to fluids. This causes edema, or local swelling of the tissue due to fluid build-up. Inflammation occurs in response to a variety of stimuli such as infection, trauma, and even temperature changes. The process of inflammation is actually a beneficial process that the body uses to respond to tissue damage and repair local tissues. However, since inflammation is so strong and can potentially damage healthy tissue, it must be tightly controlled and eventually turned off. The body has developed systems that turn off the release of pro-inflammatory mediators and eventually resolve the localized inflammation. Problems arise when this natural negative feedback (OFF switch) mechanism does not work. When inflammation runs rampant, it can cause damage to the healthy tissue and result in significant fibrosis. Frozen shoulder syndrome is thought to occur when inflammation in the shoulder gets out of control and leads to excessive fibrosis.

Soft tissue inflammation and myofibroblasts

It is still unknown how the inflammation in the shoulder’s soft tissues occurs. Some have speculated that this occurs due to excessive movement, infection, or some sort of trauma such as a bruise. Interestingly, people with diabetes have a higher risk for developing frozen shoulder. This suggests that the underlying, chronic inflammation associated with diabetes may be responsible for either the onset, or perpetuation of frozen shoulder. In any case, the initial inflammation is followed by a fibrotic reaction in which the tissue produces an excessive amount of fibrotic factors that stiffen the soft tissues. These factors can include proteins such as collagen and fibronectin and they are mainly produced by a cell called the fibroblast.

Fibroblasts are the main structural cell in soft tissues and play an important role in tissue repair and regeneration. Some researchers have shown that fibroblasts produce these fibrotic factors using histological staining of soft tissue biopsies from patients with frozen shoulder–although the mechanics of how this occurs is still poorly understood. In any case, current models show that the initial proliferation of the fibrotic cells and their production of fibrotic factors in the capsule of the shoulder joint is then followed by the transformation of the fibroblasts into myofibroblasts. Myofibroblasts are a specialized type of fibroblast that have the capacity to contract using specialized protein structures called the actin-myosin complex. In fact, if researchers remove myofibroblasts from wound tissue, they can get them to contract in a petri dish. Myofibroblasts work together with a group of tissue enzymes called matrix metalloproteinases (MMPs) that chop up matrix proteins and release the fibrotic factors. In other words, myofibroblasts and MMPs form a balance (yin and yang) of fibrosis, with one building the fibrotic tissue and the other dismantling it. When this balance is interfered with, fibrosis goes unchecked and frozen shoulder may develop.

Myofibroblasts are important cells in wound healing and we need them in order to close wounds but in frozen shoulder, they appear to be uncontrolled and their contractility may be the very thing that causes the stiffening associated with the condition. Normally, myofibroblasts are lost after a wound closes through a complex process called “programmed cell death” or apoptosis. In frozen shoulder, however, proper myofibroblast apoptosis may not occur and therefore, these cells are left to create more fibrosis and further contract the tissue. Some of the drugs that are used to treat frozen shoulder target these processes. At the same time, some drugs that interfere with this process can cause tissue fibrosis very similar to frozen shoulder. Marimastat, a synthetic matrix metalloproteinase inhibitor, can induce conditions very similar to primary frozen shoulder syndrome.

Fibrosis causes restrictions in movement

Although the underlying immune responses associated with frozen shoulder are still being characterized, our understanding of the biomechanical features of the condition are much more comprehensive. Frozen shoulder is characterized by a profound restriction of the anterosuperior capsule of the shoulder joint. This involves two ligaments (superior glenohumeral and coracohumeral) as well as the rotator interval (see shoulder joint anatomy) This reduces the external rotation of the shoulder, restricting outward movements. In some severe forms of frozen shoulder, this can also cause restrictions in the internal rotation of the shoulder. This disorder is one of the most common muscular-skeletal problems seen by orthpaediatrists.

But what causes the inflammation and fibrosis? Where is the beginning?

How does the inflammation begin? And once it begins why doesn’t it go out of control? Despite much research into frozen shoulder, we still do not know how it begins and although there are many theories, there is still a considerable amount of controversy even among specialists. Some believe that physical trauma can cause the initial inflammation of the condition. In a recent study published by a group of doctors from the Department of Orthopedic Surgery at the William Harvey Hospital in the UK, it was suggested that using certain types of sutures during shoulder surgery can increase the risk of developing frozen shoulder (Sivaloganathan et al., JRSM Open, 2015). Similarly, others have suggested that certain types of surgical procedures in and of themselves can also lead to the greater risk of developing frozen shoulder.

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