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Neural Prolotherapy



Every good regenerative medicine specialist should have a varied arsenal of treatment plans for chronic musculoskeletal conditions, and Neurofascial Prolotherapy (for simplicity’s sake referred to as NPT hereafter) is a very useful tool in the treatment of certain kinds of musculoskeletal pain. NPT goes by several names, including Neural Prolotherapy, Lyftogt Technique and Perineural Superficial Injections, to name a few. NPT was a technique developed by Dr. John Lyftogt*, a physician from New Zealand in the early 21st century and is now in use worldwide for successful treatment of ailments, including many considered chronic and untreatable.

I had the opportunity to meet Dr. Lyftogt several years ago at a conference, and he told his story of being an athlete and lover of rugby. Like many players of that sport, he suffered from chronic calf and Achilles tendon pain, but was able to cure himself by the superficial injections of low concentrations of dextrose, a natural sugar, injected along the path of cutaneous nerves (sensory nerves that lie just under the skin).

Today, NPT is practiced in multiple clinics in the United States and around the world. It’s a great example of a very low-risk, high-reward procedure that’s easy to perform and very well tolerated.

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.


Dr. Lyftogt took an idea from the mid-19th century called Hilton’s Law to help piece together the idea that a lot of chronic pain people deal with is due to neurogenic inflammation, or irritation of the tiny nerves under our skin, called cutaneous nerves. Hilton’s Law comes from John Hilton, a British surgeon who was considered the foremost anatomist of his time, earning him the nickname “Anatomical John,” as he spent a great deal of his time dissecting cadavers and diagramming the body’s structures.

Dr. Hilton noted in a series of medical lectures in the 1860s that the nerve supplying a muscle also innervates (provides nerve fibers to) the joint as well as the skin overlying that muscle. So, if you have pain originating from, say, the superficial nerves of your elbow from chronic muscle tightness and overuse, old trauma, etc., those same inflamed nerve fibers will cause pain in the deeper muscle and even around the joint. Reducing the inflammation by NPT injections will lead to reduction of pain in the underlying muscle and joint.

Nerves that are chronically irritated, often due to of an area of constriction (like putting a noose around a segment of a wire) don’t behave normally.

They secrete neurotransmitters such as Substance P, CGRP (calcitonin gene-related peptide), and nitrous oxide (NO) that increase inflammation and ramp up the perception of pain. Low concentrations (around 5% solution) of natural sugars such as dextrose or mannitol seem to solve this problem by binding to calcium channels that inhibit the body from releasing these substances and facilitating the release of anti-inflammatory neurotransmitters such as somatostatin and galanin. Deep branches of our nerves that provide sensation to our joints send out unmyelinated (non-insulated) nerve fibers that sense pain, called C fibers. These C fibers send branches to many locations, including blood vessels, joint cartilage, ligaments, and tendons.

As we saw above by Dr. Hilton’s findings, irritation of nerve fibers anywhere along their length can result in the nerve sending pain impulses both in the direction the nerve normally sends signals, called the orthodromic direction (for sensory nerves, that means towards then central nervous system—the spinal cord, then the brain), and in the opposite (antidromic) direction.

The orthodromic pain impulse leads to a reflex action of muscle spasm, much like the muscles in your forearm and hand will contract if you touch a sharp object, only with the contraction being prolonged. The antidromic pain impulse (going from “central” to “peripheral,” as with from the shoulder to the arm) travels to the blood vessels to release substance P to cause pain and swelling. If this condition becomes chronic, the tiny nerves surrounding the nerve, called nervi nervorum, will also release substance P and CGRP, leading to worse pain and soft tissue swelling.

Nerve diagram

Chronic constriction injury (CCI) of a cutaneous nerve. The nerve is entrapped and constricted in the soft tissue under the skin called fascia, leading to swelling and production of painful nerve impulses down the length of the nerve, at times as far down as the underlying muscles and joint.

If the source of the pain is in the cutaneous nerves, NPT stands a good chance of relieving the problem. The way you determine this is my palpating along the pain area and feel for discomfort to touch over soft tissue and superficial structures. If you can’t elicit pain with palpation/ pressure, then consider an alternative treatment to NPT.

NPT injections typically take several treatments to see good results. On average, I see patients for these around once a week for four to eight weeks. The key is to look for improvement of symptoms from one treatment to the next. This can happen either by the patient telling you that the overall pain is improving, or that certain areas of pain are gone, with others persisting. One patient told me that NPT on his low back that covered most of his lumbar spine and down to his buttocks caused his areas of pain to shrink “from the size of Texas to the size of Rhode Island!”


Injections of substances such as dextrose and mannitol that just break the skin rarely cause side effects beyond local tenderness and bruising. Medical grade dextrose is made from corn, as is mannitol, typically, although it can be extracted from most plants, some trees, and even seaweed [Lawson, P. (2007) Mannitol. Blackwell Publishing Ltd. P 219-225]. So allergic reactions are extremely rare.

As I mentioned before, I’ll typically add some lidocaine for anesthetic effect with these natural sugars, because it numbs the tender areas quickly (its onset is typically within 20 to 30 seconds), creates a larger area of numbing than the sugars alone at each injection site, and gives the patient a window of an hour or two of good pain relief so they can get on with their day.

My only words of advice to patients post- procedure (besides the obvious one of keep the injected sites clean until the skin heals the puncture sites) are to take it easy while the lidocaine is still active. “Numb” may mean “less pain” or “pain free,” but numb is a false friend that won’t register and can cause damage to your effected areas by not detecting stress and signaling you to stop activity. As we talked about before, pain is usually your friend. It’s the body’s way of telling you not to overuse a damaged area and make it worse.


Much like traditional Prolotherapy, NPT has a vast application in the treatment of musculoskeletal conditions, from neck, knee, and low back pain, to tennis elbow and chronic myofascial pain over soft tissue (soreness over skin and underlying muscle). It even has applications in the treatment of migraine headaches, post-herpetic neuralgia (pain from shingles infection), and frozen shoulder.

Is it always successful? Of course not. But as injections go, it’s truly one of the, if not the, most easily tolerated and safe procedures available. And if done correctly, it follows the dictum of the Hippocratic Oath that every physician takes upon getting his or her degree: First, do no harm.

It should be noted that NPT has its share of naysayers, and a quick Google search will find at least one or two articles blasting it as nothing more than voodoo medicine or pseudo-science. While I believe everyone is entitled to his or her opinion, the common theme I see with such detractors is a lack of willingness to reach out to NPT practitioners and their patients, and see what kinds of results they get with this procedure, particularly those “hopeless” patients who had exhausted other options and are left to popping pain pills and repeated steroid shots. While the research and articles in medical literature on NPT are not extensive (keep in mind, Dr. Lyftogt first lectured on this subject in the United States in 2006), I have yet to meet an NPT practitioner who has not had some amazing success stories with these simple injections.

In medicine, just like the real world, results matter. You can make a reasonable argument that something may not be verifiable because it has not been studied extensively in the medical literature. My answer to that is that my wife and two sons will likely appear nowhere in any medical textbook or periodical, yet I’m quite sure that I’ll find them at home waiting for me when I return from work. That’s proof I see every day.

For the athletic population, I use NPT a lot for sore knees, chronically tight or “pulled” muscles in the neck, low back, and calves. While these patients may still require some rest and even rehabilitation after treatment, NPT goes a long way to reducing pain and speeding up the process. As I’ll talk about below in my own example, it can be the game changer that makes a problem area go from good to great.



Marcy was a 29-year-old lady who came to see me for chronic migraine headaches she got three to four times a week that had bothered her since high school, but had gotten worse since the birth of her second child almost two years prior. She also noted pain in her upper back in and around her shoulder blades and neck since a motor vehicle accident five years prior. Her headaches were affecting her ability to read and fulfill her job functions at a busy law firm, made it hard to think clearly at times, and were putting a stress on her relationship with her family and friends.

Her neurological examination was normal, but she did show some tenderness to pressure over her trapezius muscles (the thick muscles neck to the neck running to the shoulders) and the lower cervical paraspinals (muscles that help to hold the head up in the neck). I suggested we try a version of NPT called a Crown of Thorns technique that involves tiny injections around the skull, and if this was not effective or partially effective after a few rounds, we could move on to Prolotherapy to the cervical spine. She tolerated the procedure well and we agreed to follow up in a few weeks.

When Marcy came back to our office a month later, she said with a smile that after two days of discomfort after her procedure she had been headache-free since, and rated her pain as ZERO out of ten. Her neck pain was not a factor and she had not had to take any medication for headaches. I have subsequently seen her for treatment many months after her initial injection, and after a correspondence shortly after this second round, she confirmed that once again her headaches were again completely gone!


Tammy was a 32-year-old lady who complained of severe pain and tightness in her right calf for 48 hours, worse with standing and dorsiflexing her ankle (lifting her foot up from the ankle joint). Her job involved a great deal of walking, and she stated she aggravated it with overuse. When I examined her, she showed a lot of tenderness over the area of the sural nerve, which courses along the lateral, or outside of the back of the calf and comes down to the lateral ankle.

Tammy received one treatment of NPT (mannitol with lidocaine) and reported significant pain relief and ability to walk normally the next day! In a few days’ time, her pain was completely gone. Tammy’s case was a good example of how even acute issues can respond well to NPT. For an athlete, this can mean the difference between playing or being stuck on the sidelines.


Lorraine was a 71-year-old lady with a diagnosis of trigeminal neuralgia, a painful irritation of the nerves that supply sensation to the face and jaw, which she had been suffering from for over 10 years. In Lorraine’s case the pain was centered mostly next to the right upper jaw near her nostril, causing sensations that varied in nature from burning, tingling, and even electric shock-like sensations. She also had severe hypersensitivity of the skin in this area, and something as mild as running a finger over it could cause discomfort. It even affected her ability to chew food and talk for long periods of time. She noted that it would be nice to be able to wash her face and “not worry about setting off twinges [of pain].” She had tried a bite guard and Lyrica (a medication for nerve pain) without relief, and noted that only high doses of carbamazepine (a medication used for seizure control that can be used for stubborn nerve pain) kept it at bay. Finally, she noted a painful clicking and popping of her jaw when she talked a lot or ate.

Lorraine’s exam was fairly normal except a feeling of crepitus (crunching/ clicking) at her TMJ (temporomandibular) joint, where the jaw “hinges” to the skull, and severe sensitivity to light touch over the area she described. She fit the diagnosis of trigeminal neuralgia as we discussed above, as well as TMJ disorder, caused by a laxity of the ligaments that control the jaw and sometimes the fibro-osseous junctions of the jaw muscles as well (the master and temporalis).

We discussed the option of Prolotherapy for her TMJ pain (which was likely linked to her trigeminal neuralgia), but Lorraine (understandably) wanted the most direct treatment for her neuralgia, so we agreed to try a series of NPT injections along the path of the trigeminal nerve’s second division, which is the one that covers the upper jaw, cheeks, and side of the face above the upper lip and below the eye sockets.

Lorraine noticed a positive effect on her pain reduction after her first injection. She came back a week later for her second one, and over the course of a month and a half proceeded to have a total of six rounds of NPT to this area. She stated that her pain had lessened and that the time in between flare ups was increasing, but she would get a twinge now and again that traditionally signaled the pain coming back. Overall, she was very happy with the down time the injections afforded between attacks.

Since those initial six injections, Lorraine has thankfully required only two more rounds of NPT, one that came over two months after her six- shot series, and the last one over three months since that one. At her last visit she stated that in the last few months she is able to touch the formerly sensitive area by her nostril, wash her face, put on makeup, etc., without pain, and that NPT had worked better than anything she had tried in the last decade for her condition.

I told Lorraine what I always think of when someone’s doing better: that I hope we never have to see her from a professional standpoint again, and if she stops by, it’s just to say hi and let us know that she’s well.

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.


Yep, it’s me again. I’m sure you guessed I’d be an NPT patient as well by now, right? I’ll keep my story short:

I’d already mentioned the chronic knee pain I suffered from in my early 40s, which did improve, thanks to Prolotherapy, then PRP, weight loss, and better exercise. But I still had lingering sensations of aching and tenderness over certain bony structures that got worse with too much squatting/ bending of my knees.

I discussed my history with a friend and colleague of mine, Dr. Mark Cantieri. Mark is an amazing physician and longtime regenerative medicine specialist who has taught me a lot (if you’re anywhere near Northwest Indiana, not far from Chicago, go see him), and as we had just been discussing NPT, he told me that the answer was right in front of me. When I explained where the tender areas were, Mark asked me if I knew the corresponding nerves that innervate the skin of those areas. I said I did. He then asked me if I knew how to inject those nerves with a solution of 5% mannitol. Again, I said “sure,” to which he replied, “So what are you waiting for?”

Sure enough I felt better within a few minutes of my first round of injections, and after four rounds of NPT to my knees over three weeks, I was bending my knees and getting into positions I hadn’t been able to do comfortably for a long, long time. Since then my knees have been great overall, aside from an occasional twinge when I overwork them (which can happen to anyone). NPT was the game changer that took me from “good” to “great.”

walking on the beach



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