“Things are transformed one into another according to necessity, and render justice to one another according to the order of time.” – Anaximander
Prolotherapy is a controlled injury to the enthesis.
The enthesis is defined as the area where tendon, ligament, or joint capsule inserts into the bone and acts to transmit the tensile load from soft tissues to bone. Entheses are critical as they allow for the proper transmission of contractile forces from the muscle belly to the tendon, from tendon to capsule of the joints, ligaments, and periosteum of the respective skeletal attachment places. Forces generated by muscles, tendons, and ligaments cross joint’s lines and resulting vector of these forces minimize direct contact between bones which make a joint.
Result of this interaction-system of suspensions, tensegrity.
Elastic energy does not simply dissipate. Curves, angulations, and torsions of the bones are evolutionary necessities for the successful transfer of the elastic energy to the bones utilizing contractions of the muscles, tendons, ligaments and gravitational forces constantly acting upon the bones.
These forces generate deformational effect and as the result-elastic energy, which accumulates and stores in bones. Curved, angulated, twisted structures (bones) are able to accept, accumulate, transform, store and release energy for various functions. Tensile forces of ligaments, tendons, and muscles generate deformational stress within the bones, which transform into elastic energy and then spread throughout the bone’s structures.
Elastic energy is utilized for metabolic needs of the bone and bone marrow and external tasks -transmit energy back to entheses to maintain tensegrity of the locomotion system.
Biochemical composition and contribution of various constituents of the locomotion system are changing ontogenetically.
The various constituency of locomotion system provides different functional contributions to the function of the whole system and changes occurs throughout life.
Factors affected these functions are
-Injuries and overuse
-Infections and autoimmunity
Aging=result of the above factors
There are two types of entheses:
Fibrous entheses attach directly to bone or periosteum primarily via fibrous tissue, which is similar in structure to the tendon mid-substance.
Fibrocartilaginous entheses attach to bone through a layer of fibrocartilage which acts as a transition from the fibrous tendon tissue. There are four zones of Fibrocartilaginous entheses:
1) Pure dense fibrous connective tissue
Pure dense fibrous connective tissue is composed of pure tendon and is heavily populated by fibroblasts1. The mechanical properties of this zone are similar to those of mid-substance tendon, with its composition consisting mainly of linearly arranged type I collagen as well as some type III collagen, elastin, and proteoglycans within the ground substance surrounding the cells.
2) Uncalcified fibrocartilage
Uncalcified fibrocartilage is an avascular zone of uncalcified, or unmineralized, fibrocartilage populated by fibrochondrocytes and consisting of the proteoglycan aggrecan and types I, II, and III collagen. In most long bones, fibrocartilaginous insertions are found on the epiphyses and apophyses in contrast to the fibrous insertions routinely found on metaphyses and diaphyses.
The differences in the relative positions of these insertions have an important impact on the mechanical function of the uncalcified
3) Calcified fibrocartilage
Calcified fibrocartilage is an avascular zone of calcified, or mineralized, fibrocartilage populated by fibrochondrocytes and consisting of predominantly type II collagen as well as aggrecan and types I and X collagen. This zone represents the true junction of the tendon to the bone and creates a boundary with the subchondral bone
Bone consists of osteoclasts, osteocytes, and osteoblasts residing in a matrix of type I collagen and carbonated apatite mineral.
Various factors will modify the structure and function of the enthesis: autoimmune, infections, toxins, metabolic, genetic, mechanical etc.
Again, PROLOTHERAPY IS A CONTROLLED INJURY.
Injections of the enthesis activate signaling pathways to the CNS which initiate the neurohumoral response
Extravasation of the blood initiate oncotic gradient.
The hypertonic solution of dextrose injection leads to osmotic effects.
These factors activate:
1. adult stem cells that are found in adult tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body.
2.multiple physiological systems. These processes take place in the tissues, working simultaneously to control and regulate complex physiological reactions. One such response to to the controlled injury (Prolotherapy) is an inflammatory stage of the connective tissue healing directed by cytokines, or growth factors, including PDGF and TGF-β. These growth factors are essential for cell chemotaxis, proliferation, differentiation, and extracellular matrix synthesis during the healing process
Stanley Miller and colleagues wrote:
“Organs are composed of collections of differentiated cells that perform discrete functions. An underlying homeostatic system exists to replace senescent differentiated cells and tissue loss following injury. This hierarchical system typically involves several stages of cells that have decreasing reproductive capacity and simultaneous increasing commitment to differentiation. The most primordial cell in the hierarchy, the stem cell, has the ability to reproduce for the life of the organ. It is typically undifferentiated, divided infrequently, and often resides in specialized physical locale termed a “niche.” Following division, a stem cell will give rise to, on average, one daughter stem cell that will remain in the stem cell niche and another, variously termed a transit-amplifying cell in most epithelial studies…These rapidly proliferating cells undergo further reproductive divisions…and progressively commit irreversibly to differentiation along one or several lineages”
These processes lead to the proliferation of fibroblasts and their subsequent transformation into myofibroblasts. These are the key components to mechanical forces. Fibroblasts are the main fascial cells that respond to different types of strain by secreting of proinflammatory cytokines, growth factors and extracellular matrix proteins that enhance proliferation, migration, and angiogenesis. These results in stimulating wound healing- cartilages, ligaments, capsules, tendons, muscles, nerves, vessels.
Mechanical forces in the form of needling, osmotic, oncotic, hormonal and chemical stresses, various forms of Osteopathic manipulative treatments induce fibroblasts to strain and subsequently initiate the cascade of healing reactions. Magnitude, pattern, and duration of the mechanical forces play an important role in the induction of the healing expression of the fibroblasts and are not linear.
Myofibroblasts possess significant contractile abilities, which generate tensile forces at the site of injury (enthesis).
Mechanotransduction is the biological process where cell sense and respond to mechanical load. This process occurs when the body converts mechanical loading into cellular responses.
Long-term medical, biologic and engineering studies have to lead to the discovery of a general biologic law governing the stimulation of tissue growth and regeneration: the law of tension-stress.
In 1963 Soviet Orthopedic Surgeon G.A.Ilizarov proposed hypothesis that “tension-stretch” plays the major role in osteogenesis. These forces allow to control and direct regenerative processes. “In the fire of distraction’s forces creating osseous regenerate infection process is cured”
These increase of antimicrobial activity is observed not only locally, at the site of tensile-stretching or tension-compression forces, but remotely, multi-segmentally.
Forces of tension increase antibacterial activity inside of the infected tissue.
Tensile forces generate highly energetic processes in the tissues.
Gradual traction on living tissues creates stress that can stimulate and maintain the regeneration and growth of certain tissues. Slow, steady tension of tissue causes them to become metabolically activated, resulting in an increase in their proliferative and biosynthetic functions. These processes are dependent on two main factors:
1. The quantity and quality of blood supply to the tissue being mechanically stressed and
2. The stimulating effects of tensile forces acting along the lines of muscular contractions because collagen fibers are generally aligned parallel to the vector of tension-stress.
The clinical application of this biologic law has enabled us to manipulate the process of healing soft tissues injuries, and therefore certain diseases and disorders of the musculoskeletal system.
Multiple clinical and scientific observations clearly confirm that the stimulating effect of tension-stress on tissue shares features with the natural process of growth.
Tension-stress stimulates osteogenesis and soft tissue histogenesis. The processes of new tissue formation and growth in adult organisms have many features in common with tissue formation during embryonic and postnatal periods. For example, skeletal muscle, under the influence of myofibroblast-induced tension-stress effects, demonstrate changes in both the energy-supplying (mitochondria) and protein-synthesizing (ribosome, endoplasmic reticulum) systems. Furthermore, the smooth muscle lining of blood vessels is also stimulated by tension-stress. Increased smooth muscle biosynthetic activity and proliferation stimulates the formation of new elastic structures and capillary networks needed for successful healing of damaged ligaments and tendons.
Changes similar to those described above also take place in the connective tissue of fascia, tendons, dermis, as well as in the endomysium and perimysium of muscle, adventitia of blood vessels, and epineurium and perineurium of major nerve trunks.
During the post-injury period, the numbers of fibroblasts increase and there is marked hypertrophy of the Golgi complex as well as enlargement of the mitochondria, the cytoskeletal microfilaments, and the granular endoplasmic reticulum. Such changes identified the fibroblasts as type II collagenoblasts-cells typical of embryonic connective tissue. Tension-stress also stimulates elongation of nerve axons; eventually, these processes grow to join one another.
The described processes are not new; different healthcare practitioners use tension – stress in their practices. Major applications are Orthopedic surgery, Prolotherapy, Myofascial release, Osteopathy, Massage, Physical therapy. Combining different modalities will improve the success rate in the management of patients with various musculoskeletal problems.
*Water is an integral part of the collagen molecule, which changes conformation upon water removal. Water plays a crucial role in stabilizing the structure of the collagen molecule and is an essential and active part of the protein unit. The consequence of dehydration is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.3 MPa generated by contractile muscles. Stresses comparable to muscle contraction already occur at small osmotic pressures common in biological environments. Water-generated tensile stresses may play a role in living collagen-based materials such as tendon or bone. Osmotic dehydration leads to the following consequences:
1.Molecule and the fibril shrink by different amounts, 1.3%, and 2.5%, respectively.
2. Dehydration is accompanied by a reduction of the gap/overlap ratio of the collagen fibrils.
3. Shrinkage of the triple-helix is inhomogeneous.
(Osmotic pressure induced tensile forces in tendon collagen)