Prolotherapy (called regenerative injection therapy by many) is injection with the goal of repairing weakened or stretched ligaments or tendons or stabilize joint surfaces affected by arthritis. The term prolo in prolotherapy refers to the effect of injection to grow (proliferate) new cells that form ligament or tendon tissue (fibroblasts) or stabilize or repair cartilage (chondrocytes).
Prolotherapy may be performed using dextrose, platelet rich plasma or stem cells. Platelet rich plasma is stronger in stimulation of repair than dextrose and stems cells are stronger than platelet rich plasma, however, accurate diagnosis and comprehensive treatment are more important than power.
Dextrose
Dextrose is the go-to solution for Prolotherapy. Dextrose, a liquid form of simple sugar, is the human form of glucose. It is the only sugar that our brains can function on and is the primary energy source for ATP which we learned about in our schooling.
A common question we hear is "dextrose is a simple sugar; how can it be helpful." Dextrose is the right-handed polymer form of glucose, which is used by humans and animals. The mirror image is L-glucose, or left-handed polymer, can only be made or used by plants.
Prolotherapy may be performed using dextrose, platelet rich plasma or stem cells. Platelet rich plasma is stronger in stimulation of repair than dextrose and stems cells are stronger than platelet rich plasma, however, accurate diagnosis and comprehensive treatment are more important than power.
Dextrose
Dextrose is the go-to solution for Prolotherapy. Dextrose, a liquid form of simple sugar, is the human form of glucose. It is the only sugar that our brains can function on and is the primary energy source for ATP which we learned about in our schooling.
A common question we hear is "dextrose is a simple sugar; how can it be helpful." Dextrose is the right-handed polymer form of glucose, which is used by humans and animals. The mirror image is L-glucose, or left-handed polymer, can only be made or used by plants.
During injury, the ligaments that hold bones together and the tendons that hold muscles onto bone are weakened and repair incompletely (about 80% or so). Repeat injuries cause weakness to increase to the point of starting pain. Unlike in diabetes where glucose is high in the circulation but not outside of ligament and tendon cells, in prolotherapy blood sugar is not affected but dextrose is elevated about the ligament and tendon cells. An important effect of dextrose injection is to cause new growth of ligament and tendon tissue. Dextrose cannot be brought into the cell without automatically turning on repair signals by the ligament or tendon cells (called fibroblasts). Dr. Reeves has published research indicated that dextrose prolotherapy does not likely work by causing inflammation, because dextrose levels drop quickly after injection. [1]
Dextrose prolotherapy is the most commonly performed method for a number of reasons:
- It is safe, comparable to the safety of acupuncture, as long as physicians have been fully training in needle placement methods.
- It uses very low cost and readily available sterile dextrose solutions.
- Prolotherapy using dextrose is the only method of prolotherapy that can be used to treat complex cases that require treatment of many areas simultaneously for benefit.
- Dextrose has proven ability to grow normal ligament tissue. Studies in the Mayo Clinic Orthopedic Research Laboratory showed doubling of ligament thickness with dextrose injection compared to saline injection.
- Dextrose has been shown to stimulate some cartilage cell growth. Note, this does not resurface joints but the goal is to stabilize and calm the joint surface in arthritis.
- Research on dextrose prolotherapy is the least affected by drug company or device company bias because there are no profit motives to publish positive results. Research is typically done by physicians sacrificing their time and personal finances.
- Other than the information offered by clinical trials, which is considerable, a general estimate is often made that 80% of patients should respond that have failed other treatments. That is a reasonable statement, but with three qualifications. First, complete elimination of pain and complete functional restoration are to be strived for and that depends on complete diagnosis and complete treatment. Second, the use of perineural injection treatment (PIT) has substantially affected the success rate in combination with prolotherapy, and its application is spreading worldwide as well. Third, pain is from nerve inflammation and there are multiple environmental contributions to nerve inflammation and these may need to be identified in the most difficult cases. A general observation by this author is that the percentage of responders continues to improve as expertise with combination treatment grows worldwide, and with more complete identification of environmental factors.
Platelet Rich Plasma (PRP) is a stronger solution of prolotherapy designed to stimulate healing. We carefully draw tubes of blood and use special equipment to spin and separate the red and white blood cells. The most common type of PRP, currently, is one in which the red cells and white cells have been removed, leaving the clear plasma of the blood with platelets. Platelets contain growth factors that are already made and ready to begin work immediately when they are activated. If PRP is injected in an area of disrepair, you have a very powerful stimulant for healing. In the PRP are also some stem cells. The exact potency of PRP has not been compared with dextrose but PRP is likely more potent than dextrose. However, it cannot be used in large areas because it can only be made in a limited volume.
There are several things to consider when deciding whether to use PRP. One is COST. PRP is more expensive to use for two reasons.
- It takes more time to make than dextrose, so it takes more personnel time.
- Some doctors use kits to make it and specialized centrifuges, which can be costly.
When we see patients we think about the following question, "Since PRP is likely stronger but also costs more to use, where will it be more cost effective to use it?" So, if it's stronger, even though it is more expensive, it may be more cost effective to use. It may also achieve results with less treatment for someone with more limited time. This is where careful individual consideration of the unique needs of each patient is important.
One other consideration is whether there are areas of nerve compression or neuropathy, since PRP may be more helpful in treating nerves than dextrose.
Stem Cells, Ozone and other options
In addition to dextrose and PRP injection, ozone injections are likely helpful, but ozone use has minimal research evidence thus far and will not be emphasized. Stem cell use is likely the most powerful approach for benefit in the treatment of small areas or individual joints, but its cost effectiveness is uncertain at this point, and for that reason its use will not be emphasized on this website. It is Dr. Reeves experience that full diagnosis and full treatment with a combination of dextrose and PRP injection about ligaments, tendons and injections (prolotherapy) and about nerves (perineural injection therapy and hydrodissection) offers the most cost-effective approach to the most difficult pain conditions.
At this time I do not personally find sufficient evidence in the literature that stem cell use in musculoskeletal medicine and chronic pain is cost-effective, and thus I have not begun their use. However, those for whom finances are not an issue, please do not let me discourage you from the use of stem cells, because stem cells are powerful, and have little downside other than expense. However, if you become frustrated with results, the most important thing to keep in mind is that a complete diagnosis of pain sources and treating them thoroughly, including both connective tissue (ligament/tendon/cartilage [joint]) and nerve sources, is crucial and is rarely done. By way of illustration think of being attacked by 4 people at once. If you address just one of them with a powerful method but miss the others, you MAY scare the other 3 off for a while, but they will be back, and you have not truly solved the problem. These brief comments are written for the majority of people for whom comprehensive treatment, not power, is the key, and for whom the cost of stem cell use is prohibitive. In the meantime I do have several colleagues currently using them and am certainly happy to refer patients to them if I believe that would be the most effective treatment.
[1] Rapid Decrease in Dextrose Concentration After Intra-Articular Knee Injection: Implicationis for Mechanism of Action of Dextrose Prolotherapy.
