Connective Tissue
In order to understand just how Prolotherapy helps relieve chronic ligamentous and tendon pain, it is necessary to know just what makes up these structures.

Collagen is the major component of most connective tissues and constitutes approximately 25 percent of the protein in mammals. For practical purposes the physical behavior of ligaments and tendons is mostly dependent on their main component, collagen, and the ground substance in which the collagen fibers find themselves-water and Proteoglycans. The cells and the connective tissue structures in which the cells find themselves (water, collagen, and proteoglycans) are the key components to understanding Prolotherapy, inflammation, and healing.

The Connective Tissue Cells
The majority of cells in connective tissues, such as muscle, fascia, ligaments, tendons, and cartilage, are fibroblasts and chondrocytes. Fibroblasts synthesize collagen and proteoglycans in the muscles, fascia, ligaments, and tendons; whereas, chondrocytes (see research paper) are involved in the formation of cartilage.

Fibroblasts and chondrocytes (see research paper) are considered stable cells in that they normally do not replicate often, but can regenerate connective tissue and cartilage at a rapid rate in response to a stimulus.

The connective tissue cells (fibroblasts, chondrocytes, and osteocytes from bone) that secrete the connective tissue matrix are quiescent (quiet) in adult mammals. However, all proliferate in response to injury, and fibroblasts, in particular, proliferate widely, constituting the connective tissue growth in response to inflammation.

This concept is vital to understanding Prolotherapy. The collagen in ligaments, for example, is thought to remain relatively inert metabolically with a half-life on the order of 300 to 500 days. This is a turnover rate even slower than bone collagen.

This means that half of the collagen contained in ligaments and tendons is produced only every one to one and a half years.

Of course, if the body sustains an injury or receives Prolotherapy this all changes. Both the original injury and Prolotherapy stimulate the inflammatory process, specifically fibroblast and chondrocyte proliferation.

If fibroblasts, for example, were not encouraged to replicate it would take them one to one and a half years to repair half of the ligament and tendon injury every time an athlete was injured.

Fortunately, fibroblasts and chondrocytes can be stimulated to replicate at a much faster rate by both the original injury and Prolotherapy.