WHAT EXACTLY IS PROLOTHEAPY, AND HOW DOES IT WORK?

The word “prolotherapy” derives from the Latin “proli” meaning to regenerate or rebuild. Simply put, it’s the injection of a substance or substances into a damaged area with intent to cause an inflammatory response, which ultimately leads to repair of tissue and improved joint stability, i.e., healing and pain reduction. I’ll explain.

Inflammation is important for successful healing, but unfortunately, our support structures such as ligaments and tendons have a relatively poor blood supply to aid in that process. Prolotherapy, simply put, mimics an injury by the injection of substances that are safe but cause irritation to the injection area. The most common substance used today is dextrose, a 10-chain sugar (10 glucose molecules strung together) made from corn that’s diluted down to around 17% or so for extra-articular structures (i.e., those that are outside a joint) and around 25% for those that are intra-articular (within the joint). Another substance often used as a supplement to dextrose is Sarapin, a natural proliferant (like dextrose) that’s made from the pitcher plant. Sarapin is listed as one of the most hypo-allergenic substances known, and dextrose is typically only a concern with patients who have a known allergy to corn (I’ve never had a patient in my experience have a bad reaction to either one).

In my clinic, a typical syringe of extra-articular Prolotherapy solution consists of 3cc’s of 50% dextrose, 1cc of Sarapin, 1cc of 0.5% Ropivacaine (an anesthetic similar to Lidocaine), and 5cc’s of saline to buffer the solution and dilute the Dextrose down to around 17%. This solution will cause what is known as a hyperosmotic pressure (aka hypertonic) than the area of the body it’s being injected into. In other words, there’s more substance (solutes) in the Prolotherapy solution.

You may remember that in nature if you put a solution with more “stuff” (for lack of a better word) in it with a solution with less stuff, a flow of fluid will occur from the solution with less stuff to the one with more, as nature tries to achieve equilibrium, or balance. If I’m bringing up bad flashbacks of high school chemistry right now, I’m sorry—the lecture is almost over. You might recall a diagram of a porous box with a divider that allows regular water on one side and water containing sugar or salt added on the other. Water would move over to the sugar/salt water side from the water-only side in an effort to balance out the osmotic difference, because nature strives for equilibrium (sorry, just did the lecture thing again. Class dismissed).

When you inject a hypertonic substance such as Prolotherapy solution, therefore, you’re causing local dehydration by having the local fluids drawn into it. The body finds this very irritating, and thus induces our friend, Mr. Inflammation, to start up. In essence, the injections mimic an injury to the damaged area. What happens next are the three stages of healing as described below.

ONE: THE INFLAMMATORY PHASE

Stage one of the healing process begins with inflammation, which typically lasts a few days, possibly longer depending on the patient. This is the five-alarm fire that signals the body that there’s a problem. The Prolotherapy solution causes dehydration and lysis (disruption) of the local cells, whose contents leak out. This inflammatory response is the signal that attracts white blood cells (aka leukocytes) to prevent infection. One of the many chemicals released includes prostaglandins, which amplify the pain response in this early phase. Again, this is both normal and expected and necessary for healing. Like I was always told, “You go through a little hell to get to heaven!”

TWO: THE PROLIFERATIVE PHASE

In this phase (roughly from Day 4 post-injection to approximately two to three weeks), specialized white blood cells, called macrophages, begin to eat up and digest the cellular debris, including the damaged soft tissue at the fibro-osseous junctions. They also release hormones that attract more cells to the area, and growth factors to stimulate new blood vessels and the formation of the intracellular matrix, the biological “ground floor” or foundation of the healing area.

Importantly, they also stimulate specialized cells known as fibroblasts, which repair damaged ligaments and tendons by creation of new collagen fibers. Collagen is the basic element, or “bricks” that form the structural integrity of this strong connective tissue. At this point there is often still stiffness and soreness in the area, although most of the pain of the early days is usually gone.

It’s important to continue to limit activity, even with the decrease in pain— better does not equal healed. The collagen matrix being formed still isn’t organized and hasn’t matured, and thus isn’t strong enough to withstand the stresses of hard activity. An analogy I often make is ripping your stitches after surgery if you don’t take the time for the skin to heal.

THREE: THE REMODELING PHASE

This final stage is where the healing comes to a close. It starts at around three weeks, and may take several months to resolve. This is where the soup of collagen fibers, created by the fibroblasts and fed by the new blood supply, starts to consolidate and form the striated pattern (think of lines of flexible steel fibers stacked on top of each other) of mature ligaments and tendons.

As I mentioned a moment ago, it may take as long as several months for the healing area to regain full strength. This is the phase where you really start to notice a difference. Pain subsides. At first, it’s typically when you’re at rest. Then with progressively harder activity, and ultimately with return to your desired sport. When people ask, “How will I know I’m better?” I tell them what I’ve learned as both a patient and a practitioner: “Trust me, you’ll know.”

With successful resolution of ligament and tendon injury, a couple of great things happen:

  1. The joint is much less tender/non-tender to touch at rest. I mentioned earlier that ligaments and tendons are some of the most sensitive structures in our skeletal system when damaged. As George Hackett famously put it, “A sore ligament is a sick ligament.” Remove the damage = remove the pain.
  2. Pain with movement starts to go The aching/painful popping and clicking with flexing and extending that knee or bending over at the low back is less noticeable and often disappears. While many factors play into the degree of healing (we’ll discuss that in a bit), this second step is an important milestone.
  3. Pain with activity improves, and the patients get back to doing the things they If things go well (and they do in the majority of cases), over the course of several weeks to a few months, the athlete with the bad back gets back to lifting weights, the former college tennis player can step onto the court again, etc.

Besides the fact that untold numbers of people have benefitted from Prolotherapy over the decades, research supports it as well. Laboratory (aka In vitro) studies on human fibroblasts and chondrocytes exposed to dextrose concentrations as low 0.5% resulted in the proliferation and production of many growth factors, several of which are known to be essential to the repair, structural/functional integrity, and the growth of ligaments, tendons, and other soft tissues.

THE DOOR HINGE MODEL: HOW TIGHTENING FIBO-OSSEOUS CONNECTIONS THROUGH REGENERATIVE MEDICINE CAN SAVE YOUR JOINTS

The Door Hinge Model is probably the easiest and most common way to explain how regenerative medicine can help alleviate pain and restore function. Look at a pair of cabinet doors in your house. If the hinges are secured tightly, the doors swing smoothly and easily with no contact between them. Now, imagine the screws on the uppermost hinge on one door have begun to loosen, causing a slight downward tilt to the door.

Common sense tells us that over time, unless the screws are tightened, that hinge will continue to pull farther away from its moorings in the wood due to gravity and the stress of repeated use. Furthermore, this loosened hinge puts an additional strain on the other, intact hinges, hastening the time table for their screws to loosen as well. Obviously, this “tilt” in the unstable door will lead to contact, and eventually damage to the intact door. Over time, the coating on the doors will wear away due to the abnormal contact, and the affected door will start to fall off of its hinges.

That’s all pretty sensible, right? Now, apply that model to your joints. Take the knee, for example. What happens when the medial collateral ligament, or MCL (the ligament on the inside of the knee connecting upper leg via the femur to the lower leg via the tibia) begins to lose its integrity? With the now-loose MCL, there is abnormal lateral motion in the knee joint with every step, causing the bones to shift beyond normal range, and putting excess stress on the joint cartilage of the knee, eventually leading to cartilage breakdown. You also get abnormal loads on the remaining ligaments, which contribute to their wear and tear and ultimate loosening as well, all to the detriment of a knee joint.

*An extreme example of this type of pain can occur after a knee replacement, also known as a total knee arthroplasty, or TKA. I’ve lost count of how many people have come to my office complaining of knee pain despite this procedure and being told by their surgeon that their prosthesis looks great on X-ray, and there’s nothing more to do but address pain management.

When a TKA is done, the surgeons make a vertical incision along the front of the knee and distract the ligaments and tendon that are in the way. The quadriceps tendon, patellar ligament, and the medial and lateral collateral ligaments all get stretched (“distracted” is the term)—hard—and, like a rubber band pulled too far, lose much of their original structural integrity. Examination always shows loose ligaments that are painful to touch. As you might guess, Prolotherapy has a fantastic success rate with treatment of this condition.

For a door or cabinet, a screwdriver or drill is all we need to correct the problem. But for the human body, this is where Prolotherapy comes in. Again, recalling that ligaments, tendons, and joint cartilage have a limited capacity to heal, regenerative medicine such as Prolotherapy is the best, easiest option to use as a physiological screwdriver to tighten up that connective tissue. For that reason, I often refer to Prolotherapy as “medical spot welding” or “the natural rivet gun.”

WHAT CONDITIONS CAN BE TREATED BY PROLOTHERAPY?

Rather than give you eyestrain by listing every condition that can benefit from Prolotherapy, I’ll simply state that if it’s a musculoskeletal structure that has pain as a result of joint dysfunction, Prolotherapy is very likely to help. Here’s an abridged list of some common, and not so common conditions that have responded well to Prolotherapy:

  • Ankle pain (e.g., arthritis, chronic instability, tarsal tunnel syndrome, )
  • Knee pain
  • Low back pain (including spondylolisthesis, radiculopathy, spinal stenosis )
  • Neck pain (e.g., Barre-Lieou Syndrome, spastic torticollis, neck arthritis, et. )
  • Cervical pain and instability
  • Connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome)
  • Degenerative disc disease
  • Elbow pain (e.g., lateral or medical epicondylosis—“tennis elbow” and “golfer’s elbow,” respectively)
  • Fibromyalgia
  • Foot pain (including bunions, Morton’s neuroma)
  • Headaches (tension, migraine, )
  • Hip pain (e.g., labral tears, femoral-acetabular impingement, iliopsoas tendinopathy, snapping hip syndrome)
  • Knee pain (e.g., patellar tendinosis or “jumper’s knee,” patellofemoral syndrome or “runner’s knee,” meniscal tears, et. )
  • Osgood-Schlatter disease
  • Pelvic and groin pain (including sacroiliac pain, osteitis pubis, pelvic floor dysfunction, et. )
  • Shoulder pain (e.g., acromio-clavicular joint pain, long head biceps tendinopathy, impingement syndrome, rotator cuff tendinopathy, labral tears, “separated shoulder,” al.)
  • Sternal/anterior chest and rib pain (e.g., steronoclavicular joint dislocation, slipped rib syndrome, et. )
  • Temporomandibular joint pain, or TMJ
  • Wrist pain (e.g., degenerative arthritis, triangular fibrocartilage complex tear, al.)

SOME EXAMPLES OF PROLOTHERAPY OUTCOMES

CASE #1 – PROLOTHERAPY FOR CHRONIC BACK PAIN

Terry was a 46-year-old gentleman with a complaint of chronic low back pain for over nine years. He also experienced weakness in his right ankle and numbness in his foot from a herniated disc in his back, which led to back surgery and a partial discectomy. The surgery took care of most of the pain radiating down his leg (although he did get occasional flare ups), but his back pain and the weakness with elevating (i.e., dorsiflexing) his ankle persisted. Terry loved playing basketball; he was a former Division I power forward in college. He had a demanding profession and said he would love to get back on the court with his friends for pick-up games as a form of stress release.

After examining him, I suspected that, as with many people, much of his pain may have been coming from his sacroiliac joints. So he underwent comprehensive Prolotherapy of the lumbar spine and pelvis. When he returned four weeks later, he noted a nearly complete resolution of his low back pain. Subsequent treatments of neural therapy (we’ll touch on that in another book) for his nerve-related pain and issues lead to similar great results. He noted at his last visit that he still had some residual numbness in his big toe, but was back to playing basketball with friends. He was back to enjoying the sport he loved, and as a result enjoying life so much more.

CASE #2 – PROLOTHERAPY FOR JOINT PAIN

Linda was a 36-year-old lady with a long history of pain in multiple joints since childhood, particularly her sternum (breastbone), thoracic spine (the segment between the neck and low back where the ribs attach), shoulders, neck, and pelvis. As a young woman, she underwent more than one shoulder surgery due to chronic, spontaneous dislocation of the joint. It was only when she was an adult that she was given a diagnosis that put a name put to her condition: Ehlers-Danlos syndrome, a group of connective tissue disorders that lead to loose, unstable joints as a result of a defect in the creation of collagen.

Linda stated that she had been on Ibuprofen “forever” for her pain, and was getting chiropractic adjustments once a week on average, which gave her decent pain relief for about a day and half. After her husband and she researched Prolotherapy, she came to see me in the hope that something could be done.

Over the course of nearly six months, Linda underwent seven sessions of Prolotherapy to various areas of her body—neck, right shoulder, and scapulae (aka shoulder blades), but always had her sternum and thoracic spine and usually her sternoclavicular joints (where the collarbone attaches to the breastbone—a very painful area to get laxity in) injected.

As of her last visit, Linda is extremely happy with the results of her treatments. She stated that her sternum no longer “pops” painfully in and out of place, and she can now do activities with her husband and young children such as going water tubing, that before were impossible.

While Linda’s symptoms aren’t gone, and she would like to get injected in other areas of her body that need work (understandable, given that this disease can affect every joint), she’s told me that her quality of life is markedly better since doing Prolotherapy.

CASE #3 – PROLOTHERAPY FOR TENNIS ELBOW

When I was in my mid-20s I developed a severe case of tennis elbow (aka lateral epicondylosis) for several weeks. I was working as a laboratory assistant at the University of Chicago Hospitals, and had to move several dozen bricks used as radiation shielding (which are very dense and MUCH heavier than regular bricks). The day after I experienced severe pain over my lateral (outside) forearm that felt like an icepick stabbing me. Being young, fit, and healthy, the pain resolved over time, but flared up intermittently over the years. In my mid-40s it turned into a low-grade ache that stung me whenever I lifted heavy weights or even made a tight fist to punch a bag.

Luckily, at this point I had been practicing Prolotherapy for a while, and knew the solution was within my reach. Using a mirror, I performed Prolotherapy on my elbow twice (four weeks apart).

Within two months I was pain-free!

What my training had taught me was that the problem wasn’t just with the tendon in the forearm, like most modern medicine focuses on. It was in the ligaments underneath as well, because it’s a sure bet that the ligament instability (static stabilizers) put more strain on the tendon of the extensor muscles of the forearm (dynamic stabilizers).

Now, I don’t recommend self-injections like I did unless you have a little training under your belt. But I hope it will bring home the point for you, as it did for me, that even long-standing injuries like my bad elbow can be resolved.

Lateral epicondylosis is a wear and tear of the connective tissue of the common extensor tendon at or near its attachment at the lateral epicondyle, or the bony attachment of the tendon that allows the muscles of the forearm to extend the wrist and fingers. While not typically as dramatic appearing as this diagram shows, it can cause significant pain, swelling, and dysfunction of the elbow, wrist, and forearm. It’s important to assess and treat the structures surrounding this tendon, as damage to the ligaments around the elbow are almost always a contributing factor.

WHAT IF PROLOTHERAPY DOESN’T WORK?

This is probably the most common question people ask during consultation. Prolotherapy is not a cure-all for all kinds of pain. As with any medical procedure, you can never guarantee results. That would be dishonest, as sometimes the best procedures done on “ideal” patients by the best doctors don’t work.

One of the most common reasons why Prolotherapy does not/may not work involves the degree of pathology (damage) to a particular joint, in combination with factors related to the patient: age, overall health, other medications taken, amount of sleep, diet/nutrition status, etc.

Remember that Prolotherapy is just the catalyst that starts the healing process—it’s your own immune system that’s responsible for doing the heavy lifting. For example, a man in his mid-60s complaining of chronic knee pain for 20 years, who is 70 lb. overweight, smokes, has a poor diet, gets only four hours of sleep a night, and is on two antidepressants, an NSAID, and a three-time-a-day narcotic would not likely be a Prolotherapy candidate. A lot of things would have to be addressed first before Prolotherapy should be considered.

So, the obvious next question is: if Prolotherapy doesn’t work, what next?