How A2M Offers a New Frontier for Musculoskeletal Pain

Home → Unlocking Relief: How A2M Offers a New Frontier for Musculoskeletal Pain

Musculoskeletal pain, whether from osteoarthritis, tendonitis, or soft tissue injury affects millions, limiting daily activity and diminishing quality of life. Traditional treatments like NSAIDs, corticosteroid injections, and surgery have their place but often come with side effects or inconsistent outcomes. In recent years, regenerative medicine has introduced a promising alternative: Autologous Protein Concentrate (APC), including alpha-2-macroglobulin (A2M), a naturally occurring protein with powerful therapeutic potential.

What is Autologous Protein Concentrate?

Autologous Protein Concentrate (APC) refers to a plasma-based biologic therapy derived from the patient’s own blood. The process involves drawing blood, isolating plasma proteins through a centrifugation and filtration technique, and concentrating anti-inflammatory and protective proteins, most notably alpha-2-macroglobulin.

The Mechanism: A2M in Action

Alpha-2-macroglobulin is a large plasma protein produced by the liver. Its primary role is to inhibit a wide array of proteases—enzymes that break down proteins and contribute to inflammation and tissue damage in joint and soft tissue diseases. When tissues are injured or inflamed, enzymes like matrix metalloproteinases (MMPs) are released. These enzymes degrade cartilage and perpetuate the inflammatory cycle.

A2M acts as a molecular “trap” for these destructive enzymes. Once bound, the enzyme-A2M complex is cleared from the body, effectively neutralizing the source of ongoing tissue breakdown. This targeted inhibition of proteases sets A2M apart from traditional anti-inflammatory drugs, which often provide symptom relief without addressing the biochemical causes of degeneration.^1,2

Clinical Benefits and Evidence

Emerging research and clinical experience have highlighted several key benefits of APC and A2M injections:

Cartilage Protection: Studies suggest that A2M can slow or halt cartilage degeneration, especially in early-stage osteoarthritis.
Reduced Inflammation: A2M dampens inflammation without suppressing the immune system, making it safer for long-term use.
Pain Relief: Patients often report significant reductions in joint or tendon pain following A2M treatment.
Minimally Invasive: Because the therapy uses the patient’s own proteins, the risk of allergic reaction or rejection is minimal.
Delay or Avoid Surgery: In some cases, APC treatments have postponed the need for joint replacement or surgical intervention.

While more large-scale trials are needed, preliminary evidence is encouraging. Multiple studies have demonstrated that intra-articular A2M injections significantly improved knee pain and function over six months in patients with moderate osteoarthritis.^3,4

Applications Across Musculoskeletal Conditions

Autologous Protein Concentrate, particularly formulations rich in A2M, is being used in a variety of clinical settings:

Osteoarthritis: Especially effective in early to moderate cases, A2M injections can help preserve joint health and reduce stiffness.
Tendon Injuries: A2M may reduce tendon degradation in chronic tendonitis or tendinopathy.
Discogenic Back Pain: Emerging protocols explore A2M injections into degenerated intervertebral discs, aiming to reduce inflammation and restore disc integrity.
Post-Injury Recovery: APC can be part of a broader regenerative strategy after ligament or cartilage injury, alongside PRP or stem cell therapy.

The Future of Regenerative Pain Management

Autologous Protein Concentrate represents a paradigm shift—from masking symptoms to modifying the disease process. As research advances, the refinement of APC preparation methods and targeted delivery may further improve outcomes. For patients seeking non-surgical, biologically driven solutions to musculoskeletal pain, APC—particularly alpha-2-macroglobulin—offers a safe, personalized option grounded in the body’s own healing potential.

Dr. Manning is recognized internationally for his expertise in diagnostic and interventional musculoskeletal ultrasound and serves as a subject matter expert in the field. Dr. Manning is president and a founding member of the Naturopathic Orthopedic Medicine Academy, board member of the Oregon Association of Naturopathic Medicine, member of the Interventional Orthobiologics Foundation, and serves on the Oregon Pain Management Commission. From professional athletes to weekend warriors or those with persistent pain, Dr. Manning delivers individualized care and exceptional outcomes. He practices at Oregon Regenerative Medicine, teaches at the National University of Natural Medicine, and trains and consults other providers at Regenerative MSK Consultants. In 2024, Dr. Manning was awarded the inaugural Rising Star Award from the Oregon Association of Naturopathic Medicine, highlighting his excellence and leadership within naturopathic medicine in the state of Oregon.

References:

Vandooren J, Itoh Y. Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front Immunol. 2021 Dec 14;12:803244. doi: 10.3389/fimmu.2021.803244. PMID: 34970276; PMCID: PMC8712716.
Cuéllar JM, Cuéllar VG, Scuderi GJ. α2-Macroglobulin: Autologous Protease Inhibition Technology. Phys Med Rehabil Clin N Am. 2016 Nov;27(4):909-918. doi: 10.1016/j.pmr.2016.06.008. PMID: 27788907.
Woodell-May J, Steckbeck K, King W. Potential Mechanism of Action of Current Point-of-Care Autologous Therapy Treatments for Osteoarthritis of the Knee-A Narrative Review. Int J Mol Sci. 2021 Mar 8;22(5):2726. doi: 10.3390/ijms22052726. PMID: 33800401; PMCID: PMC7962845.
Thompson K, Shankar DS, Huang S, Kirsch T, Campbell KA, Gonzalez-Lomas G, Alaia MJ, Strauss EJ, Jazrawi LM. The Effectiveness of Alpha-2-Macroglobulin Injections for Osteoarthritis of the Knee. Bull Hosp Jt Dis (2013). 2024 Dec;82(4):245-256. PMID: 39259950.

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Chronic Pain Increased with NSAID & Steroid Use

This is truly a life changing therapy!

PRP is truly a miracle and Dr. Peterson is amazing, a true expert that really listens. Not to mention the entire staff at Oregon Regenerative Medicine are all wonderful.

I tried so many other things for my neck issues (following 7 year old whiplash injury)- chiropractic, acupuncture, physical therapy, osteopathic manipulation, massage, etc. Nothing helped past temporary relief, and PT made it worse.

After 3 rounds of PRP, I’m happy to say that my neck pain is about 90% better, dizzy spells and vision disturbances down 75%, and range of motion vastly improved.

Planning to do more sessions this year. This is truly life changing therapy! Thank you so much Dr. Peterson.

L. Stashek – December 2023

It is nothing short of a miracle

I suppose I needed a couple of days to put my head on straight and grasp the fact that I have a now healed labrum in my right hip.

While this occurrence might be something you get to experience often with patients, I admit that to me it is nothing short of a miracle. Nine years of a labral tear corrected in 3 months.

I was reminded today that just over a year ago I was looking into scheduling a surgery for it.

All of this to say, I just want to extend a huge “Thank You” to you all. I am so very appreciative….and now to fix this ankle.

B. Brutscher – October 2020

Best thing I’ve done for myself in a long time

Caring staff with my needs in mind. Treatment plan was described and benefits were optimal. Best thing I’ve done for myself in a long time. –

5 Star Review – L Virosteck, 2/23/22

“I received both Stem Cell and PRP injections. Within 8 weeks of my second injection I was hiking. Do your research, talk to Dr. Peterson … this is life changing.”

“I had almost given up on my athletic career at only 29 before I was treated at Oregon Regenerative Medicine. I have had 3 PRP injections and am getting better every day.”

“Great experience. I got prolotherapy on my jaw and ankle ligaments 4 years ago and have not had issues with the areas since.”

Both of my shoulders and my lower back were treated using prolo and PRP. I am currently pain free in those areas. Life is much sweeter when you’re not in pain all the time, thanks to Dr Peterson.

Prolotherapy helped me out so much with my sciatica and I have been pain free now for 1-1/2 months.

I had tried everything steroids injections, adjustments, PT, acupuncture and nothing worked until these treatments!

Neuroprolo

One of the irritating events in my body took two Oregon Regenerative Medicine doctors and one flash of insight to address, and the teamwork proved most efficacious!

My rambunctiously insomniac left calf, a disturbance identified by my chiropractor as an entrapped fibular nerve, stirringly alive in the daytime, became most troublesome at night with tremulous sensations like myriad tiny creatures humming and streaming beneath my skin, keeping me awake at night with their frenetic activity. Dr. Peterson got to work taming this insurrection with neuroprolo, a technique of light and superficial injections with effects far from superficial. I could already feel significant improvement, and enjoy deeper sleep, after the first session, and returned several times over the next few months for repeat performances till these symptoms abated completely.

In the course of this series, I realized in a sudden Aha! moment while out walking that I was keeping my left big toe from moving through its paces to avoid pain that had long before settled into it, thus throwing my entire left leg out of whack. Learning that feet were a side specialty of one of the doctors, I consulted him and was promptly educated in the importance of SPACE. Never an aficionado of pointed shoes or high heels, I was still inflicting my toes with crowding, and walked out from the clinic with a set of exercises, a set of toe separators, and a prescription for shoes with generous toe boxes. Before long, my gait returned to its rightful balance, cushioned and floating in Topo shoes that feel like Citroëns for the feet, when I wasn’t prancing around indoors in five-toe socks. With my fibular nerve pacified and my walking set straight, the entire issue was happily resolved, and has remained so ever since.

—Karine Pied-à-terre

Collagen Induction

When I learned about the snazzy new microneedling machine from Germany that Dr. Peterson had added to the clinic for enticing collagen to regenerate, I jumped at the chance and booked immediately, having heard of similar techniques several years ago. Less than two weeks later, I am already seeing — and feeling! — the effects from this first session, with much more to manifest over the coming weeks. Jennifer was very gentle and thorough as she worked on my face, neck, and décolleté, responding to both my own sense of what most needed reviving and reshaping and her own meticulous observation, along with Dr. Peterson’s, as he was present throughout.

Once I was numb, comfortably ensconced on the table, the process commenced, with PRP applied to open pores to intensify the results that microneedling alone can produce. Once all areas had been so treated, with a few afterthought touch-ups, my face was indulged for thirty minutes with a hyaluronic masque, very soothing and hydrating, and then I was good to go. A few days of gradual recovery from looking and feeling sunburned, a few more of not giving it all much thought, and then I awoke to the realization that my skin was suddenly looking very different: smoother, more even in tone, with pores refined, softer apparent to both look at and touch, dewy, hydrated, almost shimmery.

I’ve been a patient at CTM/Oregon Regenerative Medicine for thirteen years, benefitting from practically everything on offer, so I knew going into this that the highest standards would be maintained in aesthetic medicine, just as they are in naturopathic approaches to health and the longevity of my joints and good behavior of my muscles, tendons, and ligaments.

—Karen Christensen

Thank you for coming through yet again

Dear Oregon Regenerative Medicine, (Please share with everyone as your entire office is great.)

All medical people are kind of under siege right now. This is a scary time. It is comforting to me that I have a medical office that I can always rely on to be empathetic, efficient, friendly, and helpful when I need assistance. Thank you for coming through yet again. Take good care of yourselves.

I wanted to send a real card, but it would have been germy, so here is a virtual one with photos taken while social distancing in a park.

Susan

How PRP prolotherapy cured my headache

After two years I still had a constant headache after I got a concussion by falling on my head. I was plagued by constant headaches that would not go away no matter what I did. I had x-rays, an MRI, and I tried all the drugs that several of my doctors prescribed to me. Nothing helped and I did not want to just live on drugs. I tried different massage therapist, acupuncture, a couple different chiropractors, and all sorts of natural medicines and exercises. My headache was quite severe. After over a year of constant neck and headache pain, I was finally referred to Dr. Peterson.

The first PRP prolotherapy injections into my neck were painful, but in just three days I started feeling better. I had four treatments done by Dr. Peterson. Other than the painful treatment, I greatly enjoyed myself there, for all the people were so kind and tried their hardest to help. Now my headache is gone and all around the area of my neck that was treated feels amazing. I would highly recommend Dr. Peterson and PRP prolotherapy.

Caitlin R. Koch

Migraine headaches & hip pain

I am a 50-year-old mother of two. Several years ago I started having terrible migraine headaches which would incapacitate me for days. I was taking Topamax to lessen the frequency and also AltMax for when I would get a migraine despite the Topamax. The longer I took Topamax, the less effective is was and I was starting to get more and more migraines. Dr. Peterson has treated me twice with Prolo Therapy for my migraines and the change has been remarkable. I no longer take the Topamax, which was costing me $200/month and in the past 6 months I’ve only had 2 migraines, which were greatly reduced in strength and I was able to handle them with Excedrin. The Prolo has also had the added benefit of lessening my neck aches and making my neck feel much stronger. Dr. Peterson had also treated my hip with Prolo. I sleep on my side and was finding it difficult to get a full nights sleep because my hip would start aching, feeling like it had slipped out of place. Chiropractic didn’t help, but with Prolo my hip became stronger and no longer slips out. I no longer have the constant ache in my hip and can now sleep on my side without pain. It is such a relief to know that as I age, I don’t have to just put up with the pain, but can, in fact, make my joints stronger.

Lorri Busse

Tehachepi, CA

Old athletic injuries healed

I am often cautious when I hear someone exclaim, “that treatment was amazing” or “what a miracle”, however, hear I am saying those same words after just a few treatments of prolotherapy from Dr. Peterson. I came in to get treatment for some old athletic injuries from a water skiing accident in 1994 and many various crashes alpine skiing, plus the usual aches and pains of being athletic. I had sustained quite a bit of trauma to my sacro-iliac joint 15 years prior to seeing Dr. Peterson in a water skiing accident and then many years of alpine skiing crashes on top of overuse injuries in weightlifting, running, cycling and mountaineering. I had pain and limitation in range of motion mainly in the sacroiliac joint area, but with many areas to include shoulder joint, knee and along my sacrum and lumbar spine. After receiving just 2 treatments, I already had significant improvements in pain and motion, plus I was getting stronger. As I continued my treatments, it was as if the injuries no longer even existed and I had new supportive ligamentous support. Now, telling my story many years later, I feel I can actually say, “wow, that was a miracle treatment by Dr. Peterson.” I have competed in various CrossFit competitions, continued to cycle even harder, continue to excel in my strength, recovery from workouts and backpack and climb for days and days without pain or dysfunction.

KL, Portland, Oregon

Laboratory Associate Sales Representative

Adipose tissue graft instead of hip replacement

After 3 Orthopedic surgeons told me I needed a total hip replacement, I tried prolotherapy and PRP up here in Seattle. The pain continued and had gotten severe enough that I was making plans for surgery. Then a friend told us about adipose tissue grafts, and we saw Dr. Peterson and I had my first treatment October 2013. Within 5-weeks I was having a lot less pain, and I was able to use my hip in ways I had not been able to for 5 years. Now, 8 months later I can say I’m 80-85% back to full function and use of my hip and no pain, and I’m still seeing gradual improvement. I tell everyone with a bad knee or hip or back about my results and those that have seen Dr. Peterson have all had great results.

N.E.

Seattle, Washington

Adipose tissue grafts for foot and ankle arthritis

Dear Dr. Peterson–you been a very significant influence on my health over the last 20 years, starting with finding that my digestive problems were due to low stomach acid. None of the G.I. specialists came up with anything. The initial PRP prolotherapy back in 2009–what a difference, especially noticeable in the osteoarthritis of my thumbs and knees.

Now with the addition of adipose tissue grafts and orthobiologics to the mix, my foot and ankle has healed and I actually have realistic hope of being able to hike long distances again.

Thank you for your drive, intellect, capability, etc., etc., etc. that have brought you to this level of healing ability, gratefully,

A.G., Lake Oswego

Alp Goldsmith

Lake Oswego, Oregon

ACL tear

I was having pain in both knees and thought it was just part of growing old. After a 2nd acute hyperextension injury I was told I needed surgery. I saw Dr. Peterson and unlike the orthopedist who did a quick exam and ordered an MRI, Dr. Peterson examined my knees and figured out exactly where my problem areas were. After 3 PRP treatments, I have no pain and feel completely stable. I’m confident that my 35-year-old knees will be back to where they were when I was younger. My job as a firefighter is physically demanding and I was able to remain active throughout all of my treatments. Worth every penny! Is also way better than going under the knife! Thanks Dr. Peterson!

Firefighter in Portland, Oregon

Bone-on-bone knee cartilage

34 years ago I had surgery to remove the cartilage in my knee. Gradually my activity became more and more limited and I used to plan my day around how much use I could get out of my knee. As years went by I could be on my knee for no more than 45 to 60 min. at a time and had to rest it for several hours to reduce the pain and swelling before resuming even the simplest physical activity.

I began prolotherapy with Dr. Peterson about 18 months ago, and slowly began to see the difference in leg strength, the ability to work, and reduced wobbling and swelling of 30+ years. Now I do the usual things that others may take for granted like walking, gardening, climbing a ladder, going up and down steps without pain. I will say that I’ve regained 75% to 80% of the use of my knees and I can enthusiastically encourage those who look at prolotherapy is a noninvasive procedure with proven results.

Paul Mumford

Business analyst in Salem, Oregon

Knee arthritis

I’m walking now with no pain!
Dr. Peterson-thank you so much for the prolotherapy-I feel great! I can bend my knees with no pain-squat with no pain-I am walking out with no pain!

Rachel Lewis

Retired in Milwaukie, Oregon

TMJ

I’ve had considerable stiffness and facial spasms on the left side of my face for 30 years. I read about prolotherapy in a book. Over 2-years, I’ve probably had 10 prolotherapy sessions in the TMJ, in my neck, and all down my spine. Miraculously this has healed the surgical damage I had to the nerve on the left side of my face, and I now have freedom from pain in ways no one could possibly understand. I even brought in my friend to see Dr. Peterson to repair both of his knee joints. His results were miraculous too.

Beaverton, Oregon

Sciatica & spinal stenosis

Since 2003 I’ve had intermittent sciatic pain from lumbar stenosis alongside of scoliosis. In 2008, two West Coast orthopedic surgeons offered to rebuild my spine but my friend Jean Lusk told me about her comparable medical situation resolved from PRP prolotherapy by Dr. Peterson. I agreed to 6 months treatment which lasted from February till July 2010. The conclusion is that I have achieved 80% success in relieving the pain. What I have gained has been just short of miraculous! My attending M.D. remarked that as a 75 year-old my progress was just short of a miracle!

R. Siebens

Rose Villa, Milwaukie OR

Torn hip labrum in Olympic athlete

I’ve been extremely busy since returning to the United Kingdom and my water polo team. Tomorrow will be exactly one month since my first PRP prolotherapy and my hip is definitely improving-I am very pleased with the results so far. I do still have some pain, but is less than before therapy. Sometimes it doesn’t hurt at all. I’ve played in competitions since the prolotherapy and didn’t feel my hip aching. I will be in Oregon in late December and I was hoping to get more prolotherapy on both hips in preparation for the Summer Olympics.

Lisa Gibson

British Olympic Water Polo Team

Torn hip cartilage

My name is Jene Denis, I’m 51 years old and have been an athlete all of my life. One day while running an 8-miler through the hills where live I felt my hip pop; man it hurt and I still had at least 4 miles to go. I thought my hip dislocated. I went to several doctors, most were top in their field and the diagnosis was ripped labrum cartilage in my hip, with degeneration of the cartilage and bone loss as well. The doctors were talking about hip replacement. At 51?

My Dr. here in Bend knew about Dr. Peterson’s success with hips and with each PRP injection the pain lessened and I was healing and I could not believe it. This year I skied and snowboarded all winter.

Jene Denis

Bend, OR

Sciatic Pain and Lumbar Stenosis

For eight years before seeing Dr. Peterson I had sciatic pain so incapacitating that Physical therapy did not help, and exercise was impossible as it would trigger me to be bed ridden in pain. I sought help from AMA orthopedists who diagnosed sciatica from lumbar stenosis and offered to rebuild my spine. I finally took the advice of another resident here at Rose Villa who had had success with her back and knees. After six PRP prolo treatments I achieved 80% relief of my pain, and I now exercise and take part in the activities here at Rose Villa. My attending physician remarked that my progress was “just short of a miracle”. I shall be eternally grateful to Dr. Peterson for saving me from surgery!

-Joyce Siebens, Retired, 80 years young!

Weight loss

HCG: What does this weight loss and change in diet mean for me? It’s like a rebirth. The weight was acquired so gradually, that it just snuck up on me, and I truly didn’t realize how desperately handicapped I had become. I fluffed off the limitations is just part of getting older. Well, now I am older and fat-free and feel as if I could live forever. Every move I make is a move of freedom. My mood is lighter as well, as light as my weight. The vague depression faded as I became physically lighter. I’m healthier because of the weight loss in every way my body functions. I look forward with joy to my future as a healthy, active, very happy, great-grandmother. I could not have accomplished any of this without the help of my good friend Dr. Noel Peterson. He’s been my doctor for over 12 years. His supporting and guidance kept me on the mark.

Herma Ray Baxter

Portland, OR

Unlocking Relief: How A2M Offers a New Frontier for Musculoskeletal Pain