
Prolotherapy
What is Prolotherapy?
Prolotherapy is a shortened term for “proliferative therapy” which is a shortened was of saying any treatment that stimulates proliferation and healing of tissues. These days the term “Prolotherapy” has become a very broad term that technically includes all of the regenerative therapies as they all stimulate healing in their own way. Technically platelet-rich plasma (PRP) injections are PRP Prolotherapy. Treatments to calm nerves constitute Neural Prolotherapy and there are a couple of different versions of neural prolotherapy. These include perineural injection treatment and Dextrose nerve hydrodissection. For the remainder of this page, I will use the term “Prolotherapy” to refer to the traditional and original version of prolotherapy that uses concentrated Dextrose to stimulate inflammation and healing in chronically injured tissues. Please note that traditional Prolotherapy can also be performed using other compounds that stimulate healing (e.g. Synasol, sodium morrhuate, phenol, hormones and even mesenchymal stem cells). However, these are very rarely used in Australia and hence I will only be referring to concentrated dextrose method from here.
In essence, Prolotherapy is a regenerative injection therapy that stimulates the healing and strengthening of connective tissue within damaged and painful ligaments, tendons and joints. It is a non-surgical approach to managing musculoskeletal pain and injuries by stimulating the body to heal itself.
How does it work?
Prolotherapy treatment involves injections of concentrated or hypertonic Dextrose (glucose). Concentrations above 10% Dextrose will be irritating and even mildly damaging to the issues and this, in turn, will stimulate the body’s own inflammatory reaction to stimulate healing in the injured area. Most commonly we use concentrations in the 15-25% range. We tailor the concentration to the individual patient. For some people even 12.5% can cause a severe flare of pain, while other patients may have no issue with 25% or above. There have been some recent studies that suggest that even the non-irritating concentrations (e.g. 5-10% Dextrose) traditionally used more for neural prolotherapy will also stimulate healing (Woo et al, 2021). But in summary there is no bad amount of Dextrose to use, they are all helpful in their own way. But I will always tailor the treatment to the patient to optimise their benefit while minimising flaring as much as possible.
The precise mechanism of how concentrated Dextrose stimulates healing is not exactly known. Some mechanisms that have been demonstrated in scientific studies include
Hypertonic dextrose solutions act by dehydrating cells at the injection site, leading to local tissue trauma, stimulates immune cells to trigger a healing response (Hauser et al, 2016)
This local inflammatory response then triggers
Release of cytokines and growth factors (Zhao et at, 2022)
Promotes the proliferation of fibroblasts (the cells in connective tissues that build and maintain collagen) and increased deposition of collagen (Klein et al 1989)
Klein et al demonstrated the progressive improvement in fibroblast cell numbers and improvements collagen fibre density and structure in tissues 3-6 months after being treated with prolotherapy. This means that even 3-6 months after your treatment the cells are still in the tissue continuing to repair, build and strengthen the injured tissue. An image of this can be seen below.
Klein et al 1989 - Post treatment on the right shows a greater density of fibroblast cells (purple dots) with collagen fibres in between being more densely packed
The same healing prinicples can be utilised for joints, such as for Osteoarthritis. Prolotherapy treatment in advanced knee osteoarthritis has been demonstrated to create some degree of cartilage regeneration in joints with osteoarthritis (Topol et al, 2016). This was demonstrated in biopsies taken before and after Prolotherapy for patients awaiting knee replacement for end stage Osteoarthritis. It did show some cartilage regeneration as well as significant improvements in pain and function after treatment.
Recent research into the potential mechanisms of Dextrose for neural prolotherapy provides some insight into the at least some of the healing effects and is discussed in more detail in the Neural Prolotherapy section of the website. It appears that at least some of the healing effect of traditional Dextrose Prolotherapy is also aided by the mechanisms of nerve calming (Woo et al, 2021).
Treatment schedule
After each treatment we expect a manageable flare of pain for 1-2 days after the treatment. This is the intended inflammatory reaction that we are trying to stimulate. Once this reaction has been triggered, the bodies normal healing response and phases of healing will be set in motion. As you can see below the full process from injury/inflammation to fully matured healing can take weeks to months.
Our usual method to treat patients’ is firstly to do a comprehensive clinical assessment of the patient to break down exactly where we think their pain is coming from. We then test our hypothesis by performing an ultrasound guided diagnostic block to the structure(s) using local anaesthetic. However, we will add some Dextrose prolotherapy to the injectate as it detracts nothing and if the local anaesthetic shows we are in the right spot, then hey presto, you’ve already had your first treatment! If the pain improves significantly during the period of numbness caused by the local anaesthetic it indicates that we are in the right spot and we will then continue our treatment regime targeting those areas.
If we decide that it is best to continue with exclusively Dextrose prolotherapy then we would plan to repeat the Prolotherapy treatment to the same area monthly for 3-4 treatments. An alternative to this would be that once we have confirmed the source of the pain would be to perform a single PRP injection. We find a single PRP injection for most patients will probably create as much healing as 2-3 prolotherapy treatments. For more information on PRP please see the Platelet-Rich Plasma section of the website.
However, in saying this all patients are different and some will respond faster or slower than others. Occasionally a single treatment with Prolotherapy will have the patient feeling much better and they might just return if they feel the need. Other times the effect of healing takes time and a patient might not notice much of a change over the first 2-3 months. However, in most cases even those that are slower responders will usually get a good healing and pain response over the next few months. We will continue to monitor progress and adapt our treatment plan as required throughout and after the treatment course.
The good news is that even 3-6 months after your prolotherapy treatments have finished, you will continue to get ongoing healing and improvement in the injured tissue(s) as the body continues to heal. In my experience once the problematic, damaged tissue is correctly identified and a patient undergoes their monthly treatments about half will notice a month-by-month improvement in their pain. For the other half the improvement is a little slower but usually after a bit more time (~ 3-6 months) the healing has improved to a point where they are feeling much improved. If there is still no improvement after this long or if the pain recurs after a period of significant improvement, it indicates that maybe there is more to the puzzle than just that area we have been treating and we may need to look more closely at what we need to target to get the healing we are after.
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Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016 Jul 7;9:139-59. doi: 10.4137/CMAMD.S39160. PMID: 27429562; PMCID: PMC4938120.
Zhao AT, Caballero CJ, Nguyen LT, Vienne HC, Lee C, Kaye AD. A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee. Orthop Rev (Pavia). 2022 May 31;14(4):33921. doi: 10.52965/001c.33921. PMID: 35769650; PMCID: PMC9235417.
Klein RG, Dorman T, Johnson C. Proliferant Injections for Low Back Pain: Histological Changes of Injected Ligaments & Objective Measurements of Lumbar Spine Mobility Before and After Treatment. J of Neurologic & Orthopaedic Med & Surg 1989;10:123-126
Woo MS, Park J, Ok SH, Park M, Sohn JT, Cho MS, Shin IW, Kim YA. The proper concentrations of dextrose and lidocaine in regenerative injection therapy: in vitro study. Korean J Pain. 2021 Jan 1;34(1):19-26. doi: 10.3344/kjp.2021.34.1.19. PMID: 33380564; PMCID: PMC7783851.
Topol GA, Podesta LA, Reeves KD, Giraldo MM, Johnson LL, Grasso R, Jamín A, Clark T, Rabago D. Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis. PM R. 2016 Nov;8(11):1072-1082. doi: 10.1016/j.pmrj.2016.03.008. Epub 2016 Apr 4. PMID: 27058744.