USING THE CONNECTIVE TISSUE HEALING SYSTEM

If we are going to employ the healing system to fix unhealed connective tissue damage, we need to understand how this system works (and what can go wrong with it).

‘GROWTH FACTORS’ TRIGGER HEALING

We are trying to get your body to make more collagen. You cannot simply ‘take’ collagen and have it show up where it needs to go.  It is ‘digested’ by the GI tract.  Nor can you ‘inject’ it and have it insert itself into the correct structures.  Your body has to identify a structure as ‘in need of healing’, and cells called ‘Fibroblasts’ (the only cells capable of making collagen molecules) must make these molecules in a way that they are ‘woven into’ the correct structure.  Fibroblasts are everywhere in your body.  I could not take a biopsy any place in your body and not find several.   But they do nothing unless they are ‘told’ to make collagen.  The ‘telling’ consists of a group of chemicals, collectively called ‘growth factors’, which trigger the healing cycle.  These are 40 plus chemicals which ‘run together’ and ‘act in concert’ to trigger healing.

These ‘growth factors’ live in essentially only two places in your body:  your platelets and your white blood cells.  If you have bleeding as a part of the injury, like a sprained ankle or an operation, the platelets are part of the clot, or thrombus, or scab that coats the surface of injured structures.  These then deliver growth factors directly into the injured structures.  If you do not have bleeding, the the white blood cells control and modulate the degree of collagen replacement by measuring out these ‘growth factors’ whenever they sense that tissue damage has occurred.  Prolotherapy, using dextrose or one of the 40 plus chemicals which has been shown through the years to ‘trigger healing’, uses the ‘WBC response/growth factor release’ mechanism.  Platelet Rich Plasma utilizes both the WBC and the platelets as sources of these growth factors to trigger healing.

ANTI-INFLAMMATORY MEDICATIONS HINDER HEALING

And guess what impairs the output of these ‘growth factors’ by the WBC’s?   You may have already guessed:  Non-Steroidal Anti-Inflammatory Drugs (NSAID’s) (Advil, Aleve, Mobic, Celebrex, etc.), and Corticosteroids (cortisone shots, epidural steroid treatment, Medrol dose packs, etc.).  These chemicals make you ‘feel better’ after an injury, but they make you heal MUCH WORSE, and should not be used in the context of ANY connective tissue injury, including surgery, in almost all circumstances in my opinion.   There are numerous laboratory and clinical research findings which attest to the harmful effect of these ‘standard’ recommendations for treating injuries, joint pain, back pain, and neck pain.  This is also true of ‘icing’ an area.  Ice should NEVER be used on an injury involving connective tissue.  The only indication for icing an injury is when a muscle may be actually torn.  In terms of connective tissue injuries, the pain of the injury is numbed, swelling is reduced, but healing is impaired.  If unhealed damage is the cause of pain, you might be very interested in actually healing your injuries.  Pain relief that stops healing may not be a good trade-off.

THE HEALING CYCLE:  SIX WEEKS OF COLLAGEN PRODUCTION

Prolotherapy triggers the ‘healing cycle’.  What is the ‘healing cycle’?  I am a surgeon by trade.  My day used to consist of making a hole in your belly, and rooting around and making a few more holes on the way to doing whatever operation I was doing.  At the end of the procedure, I would sew those holes up, but if we took out the sutures that same day, you would still have a bunch of holes.  But a month later everything would be sealed up and healed up enough for you to resume running, lifting, swimming, or whatever other strenuous activity you desire.  In the meantime, your body has made a vast number of collagen molecules to ‘knit together’ the holes.  Most people are generally familiar with the ‘six week sequence’ of healing following major surgery, or a major injury.  This is precisely the same process that we trigger chemically with Prolotherapy.  Most people think that most of the ‘healing’ happens during the first two weeks of this cycle, but it does not.  By the end of two weeks, you have made about 15% of the collagen you are going to make, and by the end of the fourth week, about 95%.  So you make about 80% of the collagen during the third and fourth weeks following a Prolotherapy treatment.  This is why you are generally seen at monthly intervals, because at this point you have had virtually the entire response that your body is going to provide.

DOES PROLOTHERAPY PRODUCE ‘SCAR TISSUE’?

A ‘scar’ is a random array of collagen.  But, if the structure in need of healing is a ligament or tendon, these same molecules are simply arranged in the proper parallel arrangement to match the ‘rest’ of whatever structure is being ‘healed’.   In 1999 a study was done with an electron microscope pre and post treatment to see what kind of collagen architecture was produced by Prolotherapy treatment.  How much was ‘ligament’, and how much was ‘scarring’.  The answer was a bit of a surprise.  What was seen was not only ‘pure ligament’, but the newly made collagen structure had the appearance of the ‘best, strongest’ possible ligament architecture…like marathon-runners tissue instead of ‘average’ ligament structure.  So, we apparently make a very good version of what we are ‘trying’ to make, and nothing that we are ‘not’ trying to make with this treatment.

CAN CARTILAGE HEAL?

I was taught during medical school, in the 1970’s, that cartilage does not ‘heal’.  This is because a cartilage defect in a large joint would simply sit there, unchanged, for as long as you wanted to observe it.  It was later discovered that cartilage CAN heal, but this requires that the cartilage cells, called ‘chondrocytes’, morph into a more immature cell form called a ‘chondroblast’.  This more immature cell form will then begin to produce new cartilage.  Prolotherapy with Dextrose, or with PRP, is capable of producing this effect.  Dr. Dean Reeves in 2013 published a study showing that Prolotherapy with dextrose stimulated new cartilage growth in 12 out of 20 patients treated with three dextrose treatments inside the knee capsule.  Platelet rich plasma has also been shown to stimulate cartilage growth, as it not only triggers the WBC portion of the healing system, but utilizes also the platelet portion, which would be expected to add more to the effect.  In addition, in the PRP collection and processing system that I use (Harvest Technologies), there are also about 120,000 stem cells in the injected material.  Stem cells are very well known for their ability to grow cartilage by  differentiating into cartilage cells.

STEM CELLS TREATMENT VERSUS PROLOTHERAPY AND PRP

This raises an interesting and important question:  which is better to address ‘arthritic’ knees—stem cells treatments or Prolotherapy treatments.  The answer to this depends on ‘what you think is wrong’.  I see the current move toward stem cell treatments as ‘the’ treatment for ‘osteoarthritis’ of the knee and other joints to suffer from the same problem as joint replacement.  I think that the wrong structures are the primary target of treatment.  I personally think that better results are obtained by addressing the ligament structures, and in addition perhaps growing a bit of new cartilage, as opposed to making a nice, shiny (and expensive) new layer of cartilage because…what happened to the last layer of cartilage that was there?  Oh…it rubbed off because the ligaments were not holding the joint surfaced in proper alignment.  If you do not effectively address the underlying ligament ‘cause’ of joint destruction, what do you think is probably going to happen to the ‘new layer’ of cartilage in a few years?

And, you need to consider precisely what a ‘stem cell’ treatment accomplishes, and what triggering the connective tissue healing system accomplishes at the cellular and structural level.  Stem cells are cells that can ‘differentiate’ into a variety of kinds of ‘mature’ cells, like muscle cells, gland cells, and cartilage cells (chodrocytes).  Therefore, if you want to grow cartilage, you might reasonable put stem cells into the area, and they might reasonably grow a new cartilage.   But, when you are trying to repair DAMAGED LIGAMENTS AND TENDONS, you need something other than ‘progenitor cells’.  There are no ‘ligament cells’ that ‘make’ ligament, nor are there ‘tendon cells’ that make tendon.  Tendons and ligaments are made almost entirely from collagen molecules, and are simply like a cable or a rope.  Collagen molecules are made by only one cell in your body:  a ‘fibroblast’.  Fibroblasts are everywhere.  I could not do a biopsy of tissue anywhere in your body and not find fibroblasts.  And, they are mobile.  When the ‘healing system trigger’ growth factor chemicals are released, fibroblasts migrate to the site of injury in large numbers.  YOU DO NOT NEED MORE FIBROBLASTS.  You have plenty.  What you do need is for the healing system to be triggered by the outpouring of these ‘growth factors’, which is what Prolotherapy accomplishes from the WBC’s, and what Platelet Rich Plasma accomplishes from both the WBC’s and the Platelets.  When there is an outpouring of these growth factors in a structure or structures, the ‘in situ’ fibroblasts begin making collagen to repair the structure.  Other fibroblasts migrate to the structure(s) in large numbers, and also begin to make collagen.  So, if the problem is a lack of collagen/tensile strength in a connective tissue structure, then what is required to repair this deficit is to trigger the connective tissue healing system, or Prolotherapy.

A stem cell treatment, for all intents and purposes, does not rebuild ligament and tendon tissue, nor is it intended to do so.  And, even if it did, if it is several times the cost of a Prolotherapy treatment, would it not make sense to try a less expensive, yet potentially very effective, remedy first?  We are back to the question of ‘what is wrong’ to determine which treatment makes most sense, in addition to the financial considerations.  If you are an Orthopedic Surgeon, or you are relying on the thought processes spawned by the Orthopedic Surgeons in the 1950’s and 1960’s, and think that the sum of the problem is ‘bone on bone, due to lack of cartilage, caused by an inflammation (osteo-arthritis), leading to pain, then the ‘fix’ is to attack the cartilage lack head-on with stem cells.  This would probably lead to results not unlike the ‘Orthopedic Model’ PRP results (see these results compared to Prolotherapy, and Dr. Johnson’s, results).  However, if you realize that the MAIN problem is lack of tensile strength in the ligament structure, leading to pain, and to destruction of the cartilage layer and other joint surface structures (like the meniscus), and to the bony changes that are associated with what is termed ‘osteo-arthritis’, you will direct your therapy to producing an outpouring of ‘growth factors’ in the specific ligament and tendon structures which are causing the majority of the symptoms, in addition to inducing this same process to refurbish, albeit to a lesser extent, the cartilage surfaces.  PRP has the added advantage of having about 120,000 stem cells in the injected material (perhaps 1/10 of a full stem cell treatment…not the same, but helpful, and generally adequate, for what needs to happen to restore the joint to full function and pain-free status.  It is a matter of choosing the right tool for the job.

Most people who offer stem cell treatments in large joints do not address this ligament issue, and most physicians who offer PRP treatment do not, either.  And, since much of the symptoms are coming from the ligament structures to begin with, a significant percentage of knees and other joints will probably continue to be symptomatic.  And that is precisely what I have seen in our clinic.  I do stem cell treatments, but I need to do them very rarely, and can generally get results that are as good as, and usually better than, the results I have seen in patients who have had stem cell treatments by other physicians—-with MUCH less expense.  I support the right of every American to spend more than they need to spend if that is what they want to do, but why would you want to do that?

I see the root of this situation as physicians who, while trying to trigger healing (to their credit), are still mired in a ‘traditional medical mindset’ that focuses on ‘what is seen on imaging studies’, and tries to make that sum of ‘the problem’.   Let me reiterate:  in examining over 1000 knees, around 40% of which had cartilage loss sufficient to have joint replacement recommended, not ONE of these knees with severe, or even moderate, cartilage damage did NOT have demonstrable laxity of the anterior cruciate ligament.  Not one.  Yet, I have never seen this association made in the Orthopedic literature.  And in knees with this degree of damage on films, there are always many other symptom-generating connective tissue structures.  Unless you effectively treat ALL of them, you knee will still hurt.  I have been asked multiple times through the years if I have x-ray documentation of cartilage growth following Prolotherapy treatment…and my answer is always that I have documentation of dramatic, and long-term, symptom relief in an extremely high percentage of my treated knees (and, yes there is in fact such imaging evidence available in a research study, but that is not the point). If the knees in my patients are virtually, or completely, symptom-free, do I, or the patient, care what the x-ray looks like?  Again, this question assumes a direct correlation between ‘what is seen on films’ and pain—which simply is not the case.  All of this is simple common sense….which is unfortunately, it seems, rather uncommon…

(see Dr. Johnson’s knee results compared with Orthopedic and other Prolotherapists’ research results)

STEM CELL TREATMENT AT PROLOTHERAPY NASHVILLE

In the rare situations where we cannot trigger healing and get the desired results in joint treatments with Prolotherapy/PRP, and cannot find a healing system problem which can be rectified, a stem cell treatment will be recommended as an option.  We are certainly willing to perform this procedure at any point if the patient desires, and if they have a problem that this treatment might reasonably address.  If we render this treatment, particularly as the ‘first option’, we will make every effort to treat the underlying joint instability as well, to attempt to ensure the best pain relief, functional recovery, and long-term results.  Even in our most affluent patients, though, we will not RECOMMEND this treatment except in the VERY RARE situation where other options, which hold promise of complete relief of symptoms and are MUCH more economical, have been exhausted.

HOW DO STRUCTURES END UP WITH ‘UNHEALED CONNECTIVE TISSUE DAMAGE’?

There are basically two ways that connective tissue structures loose tensile strength:   over-injury and under-healing.  Any time there is a significant injury, like a sprained ankle, the body will generally heal about 70% of the tensile strength back during the initial six weeks ‘healing cycle’.  You body also has a ‘maintenance healing’ process, with a more modest pace of collagen production, that works on an ongoing basis to replace the ‘daily attrition’ of collagen molecules.  You break and replace every collagen molecule in a given structure about every seven years, so this maintenance replacement system is actually hard at work every day.  And this is the system that gradually takes the 70% job  to 100% over the ensuing few months…if this system is working and we do not ‘get in the way’ with NSAID’s and ice.   And, since you have a lot of ‘extra’ strength in most of these structures, even if you loose some strength, you often do not ‘feel anything’, at least after the first injury in a structure.

But, if the injury is more ‘severe’, or if your tissues are already ‘abnormally weak’, or if you dramatically impair your healing system after an injury on the advice of a trainer, a family doctor, an Orthopedic Surgeon, or other well-meaning but mis-informed person who thinks that ‘inflammation is the enemy of healing’ (which is a marketing sound-bite with no scientific evidence behind it), by icing your injury and taking a handful of anti-inflammatory medication, or if your healing system is not working well for other medical reasons, like a low Testosterone level, then you might be left with a ‘non-loadbearing tendon or ligament.  If your maintenance healing system is working well and you are not too far ‘over the line’, you may find that your symptoms go away in a month or two, never to return…if you are fortunate.

If you have the misfortune to be left with non-loadbearing structures after an injury, if your maintenance healing system does not finish the repair work, you will have a whole array of possible consequences—possible muscle malfunction, joint instability, cartilage damage, etc.—in addition to pain that is intermittent, or constant.  If your healing system is not doing its ‘maintenance repair work’  what else would you expect to see?   If the daily damage is not being replaced, every connective tissue structure in the body gets progressively weaker.  One by one, thees structures ‘cross’ the line to stretch abnormally under load, and begin causing symptoms.   I refer to this as ‘multi-site connective tissue pain without a trauma history’.  Since there is often no imaging abnormality associated with this condition, and no ‘laboratory test’ that will confirm its presence, the rest of the medical community may refer to this situation as ‘fibromyalgia’ if the tenderness and symptoms are body-wide.  If the symptoms are more scattered, doctors may respond with a look of puzzlement, boredom, a raised eyebrow and the insinuation that the symptoms are somehow not ‘real’, or there may be an extensive attempt to ‘find’ the source of the problem by test after test.  At this point, one of two things happens:  either something is ‘found’ and ‘diagnosed’ as the cause of the pain (arthritis of the spine, for example, or ‘degenerative disc disease’), or ‘nothing’ is found and we are back to the various ‘looks’ that doctors give patients when the doctor has no clue.

THE CONNECTIVE TISSUE HEALING SYSTEM IS NOT PERFECT…AND THIS IS A BIG PROBLEM FOR A LOT OF PEOPLE…MOST OF WHOM DO NOT EVEN REALIZE WHAT IS HAPPENING…THAT IS, FOR MILLIONS OF PEOPLE…

The bottom line is, connective tissue healing is not perfect in many situations.  This may present no problem, or might produce enormous pain, deterioration and damage of various other structures, along with mild to severe activity limitation.  Joint pain is the second most common reason for consulting a physician in patients over the age of 40.  Chronic pain, which is defined as pain of over 3 months duration, much of which, based on my patient population, represents undiagnosed connective tissue damage, costs 635 billion dollars per year in treatment and lost productivity.  Back and neck pain, much of which represents unhealed, and undiagnosed, and potentially healable, connective tissue damage, costs 86 billion dollars per year in treatment costs and lost productivity.  And joint replacement, which as we have seen can often be avoided with proper diagnosis and treatment of unhealed connective tissue damage, costs 17 billion dollars per year.  These are not minor issues.   And, when you add the costs of imaging studies upon which diagnosis and treatment may not ‘best’ be based, to say the least, the cost of mis-understanding the role that connective tissue damage plays in body pain and further structure damage soars further.

THE HUMAN COST OF CONNECTIVE TISSUE DAMAGE

But the most important cost is in the lives of individual people.  I had 25 years of back pain and increasing activity limitation.  That was a bad situation, and 24 years of it was unnecessary if I had known the correct diagnosis and the correct treatment.  But we have had so many patients with far worse pain, far more life limitations, more ‘not-helpful’ medical interventions, more disability…the vast majority of whom have been able to ‘get their life back’ when this single issue—unhealed connective tissue damage—was correctly diagnosed and properly treated.  Does everyone have this diagnosis who has severe pain?  Of course not.  Does everyone who has this diagnosis get dramatic results from treatment?  Most do, but some do not.  But of all the things that have surprised me during my decade of Prolotherapy practice, this one has stunned me most:  the percentage of patients coming through our door, who have previously had all manner of ‘diagnoses’, who had not only ‘something’ we could treat and improve, but in whom ALL of their symptoms were from this one cause, and who DID get dramatic ultimate results, in contrast to ALL previous attempts at therapy.  This fact is why I am taking the time, on this beautiful Saturday summer afternoon, to try to communicate what I have learned and what I have seen about this very important issue.  This issue affects a lot of people.  It is a huge personal issue, and a huge public health issue.   I want to develop interest in patients, and in practitioners, to learn about this disorder.  There should be people who understand this problem correctly and who offer effective treatment for it, in every community.  Currently there are many states which do not have a single competent practitioner.

IF THIS IS THE PROBLEM, WHAT IS THE SOLUTION?

DETERMINE IF THE PATIENT IS A CANDIDATE FOR PROLOTHERAPY

Here is how I approach a patient who comes to our office.  The patient fills out a history form describing any injury or history related to their pain, previous diagnosis, test findings, and therapeutic attempts and results.  They also give historical details that may suggest one ‘healing system’ problem cause or another.  The patient then draws a picture of exactly where they feel symptoms.  These symptoms may be ‘locally generated’ or ‘referred’, and further evaluation can sort this out.  After understanding the nature of the problem from the history, and learning which specific motions or activities most trigger the symptoms, I assemble a mental list of potential structures to examine.  These structures are then palpated with a measured amount of pressure.  What would it reveal if one or more of the examined structures is ‘tender’, or ‘feels like I am pressing too hard’, or other description of ‘discomfort’?  It tells us that I am pressing on damaged nerve fibers within the particular structure, and that this structure is in all likelihood contributing a portion of the patient’s symptoms.  If I can find a structure, or group of structures, that ‘make sense’ in light of the patient’s symptoms, keeping in mind the potential of this kind of nerve damage to create ‘distant’ symptoms in defined distribution patterns, then this patient is a ‘good candidate’ for Prolotherapy.

THE ROLE OF IMAGING STUDIES IN DIAGNOSIS AND TREATMENT

Note:  I have not mentioned looking at an imaging study.  If imaging study results had resulted in correct diagnosis, and successful treatment, would the patient be sitting in front of me?  I do look at films and reports and do get certain kinds of information, like the general magnitude of the ‘rebuild’ job, but film results neither adequately diagnose the sources of pain, nor in any way give information about the patient’s suitability for this form of treatment.  Nor can imaging studies offer ‘guidance’ for thorough treatment.  Not that they should not be used by other practitioners, but if diagnosis and guidance is limited to imaging findings, treatments may well be less than thorough.  Again, a significant portion of symptoms are usually coming from structures which do not appear ‘abnormal’ on any imaging modality.

SYMPTOMATIC DAMAGE USUALLY INVOLVES MULTIPLE STRUCTURES, OFTEN DOZENS OF STRUCTURES.  COMPLETE RESOLUTION OF SYMPTOMS REQUIRES COMPLETE TREATMENT.

Many imaging results show one ‘torn’ or ‘damaged’ structure, or  few.  It is very rare to have ‘single structure’ symptomatic damage.  Your body distributes any force across a wide array of structures.  If there was enough force involved to visibly damage one or two structures, how likely is it that there was enough force to damage several structures?  I will give you a hint:  very likely.  Also, if there was enough force to break a bone, there was generally enough force to create symptomatic damage in surrounding connective tissues.  Any ‘ongoing’ symptoms more than a couple of months after trauma, or Orthopedic surgery, generally have a connective tissue origin…which will not be diagnosed unless one knows how to do the correct physical exam.  One of the primary principles of treating symptomatic connective tissue damage:  your percent of symptom relief is directly proportional to the number of symptom-generating structures that you a.) correctly identify, and b.) successfully treat.  Let me say this again, because it is SO important:  Partial, vs. thorough, identification of sources of pain IS THE DIFFERENCE between partial and complete results.

THE TREATMENT MAP:

Now I have a list, or ‘map’, of tender structures which are in all likelihood the cause of most, or all, of the patient’s symptoms.  After informed consent is obtained, all questions are answered, and the patient desires to proceed, we perform a treatment based on these ‘mapped’ structures.

HOW DO WE KNOW THAT THE STRUCTURES THAT WE TREAT ARE WHERE THE PATIENT’S SYMPTOMS ARE COMING FROM?

The healing triggering solutions (Proliferant solutions) all have numbing medication in the mixture.  This may be Lidocaine, but may also be individually tailored using other agents, like Ropivicaine and Procaine.  The point being, in addition to triggering healing, we are also numbing one structure after another.  If, at the end of the treatment, we notice the absence of ‘the patient’s pain’, even with attempts to provoke their pain or other symptoms (including referred symptoms), what would this tell us about the source of the patient’s symptoms?  Could we tell where symptoms were coming from, and where symptoms, on occasion, were NOT coming from?  Yes, we can, in a very ‘scientific’ way.

REFERRED SYMPTOMS FROM CONNECTIVE TISSUE

If a headache has a ‘connective tissue’ trigger, when we inject proliferant into that structure, the patient will often experience ‘their’ headache for  one to three minutes.  The headache will then disappear as the numbing agent takes full effect.  Or, if the patient come to the office with their headache, we can make it go away quickly once the triggering structure is injected.  We have ‘stopped’ dozens of migraines in the office within minutes of injection.  This is, as you can imagine, an very powerful diagnostic tool to localize the source of such headaches.  And if we can identify such a trigger, our success rate for reducing or eliminating these headaches is huge.  There can also be ‘non-connective tissue’ triggers for migraines which may also be operating—dietary, hormonal, etc.—so not all are completely eliminated.  But most are.

If there are referred symptoms in hips, legs, feet, shoulders, arms, or hands, and these are present at the outset of treatment, we can observe these ‘go away’ during the time that the numbing medication is active—from one to several hours.  We also have patients mention ‘feeling’ symptoms in the typical referral area when we inject the ‘source’ structure.  The reason I am so sure that there is a relationship to connective tissue, and that these symptoms do not represent the ‘nerve pinch’ or ‘sciatica’ that patients have ALWAYS been told is the ‘diagnosis’, is that we can modify them in the moment by interacting with particular connective tissue structures, and this will be consistent across multiple treatments until the symptom completely resolves, AND we see these symptoms resolving so consistently as other symptoms and tenderness resolve in the ‘source’ structures.

Muscle spasm helps us examine for damaged structures.  When a tendon is damages, the nerve fibers are firing impulses that make the muscle more tense, if not fully spasmed.  You can simply follow the ‘cords’ of muscle to the tendons on each end, and on one or the other, or both, will be tender.  And when you ‘numb’ the tendon, the muscle will promptly return to ‘normal’ tension.  And once Prolotherapy treatment has reached its endpoint, the abnormal muscle function will have also normalized.  This is also the reason that some muscles do not ‘fire’ completely, or lose strength at times.  If there is tendon damage (like in the elbow or shoulder of a pitcher) then function will be diminished (and the speed of a fastball will drop, and there is nothing the pitcher can do to overcome this situation, except heal the structure).