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1. K. Dean Reeves
K. Dean Reeves in Kansas, has some very detailed sections on his website:
2. Mooney V Prolotherapy
Mooney V Prolotherapy in the spine and pelvis: an introduction. Spine, 1995; 9(2):309-11
SPINE: State of the Art Reviews,Vol. 9, May 1995   Professor Vert Mooney, Univ California San Diego
My background in spinal care was completely traditional and, thus, very narrow. I, like every resident orthopedic surgeon in training, dreaded the low back clinic: the land of assumed psychological cripples presenting with unknowable disease, an endless series of returning patients who had had treatments that did not work. The treatments, whether surgical or pharmacologic, seemed to have no effect on a disease process that was disabling to manual workers, housewives, and even bank executives who couldn’t golf appropriately. It was clear that we did not understand many of the real causes of back pain.
I eventually became chairman of an orthopedic training program and served as president of the Orthopedic Chairmans Association. I was involved with tasks such as establishing the body of knowledge appropriate for orthopedic surgeons, developing tests, and monitoring tests. I felt comfortable that I knew what an orthopedic surgeon should know. Nonetheless, important topics went uncovered. People still had confusing chronic musculoskeletal problems, unresolved by standard exercise programs or the ever-present steroid injections. Although steroid injections were valuable, they often did not provide a persistent cure to the inflammatory lesion being treated. And we surely did not know where to operate on these patients.
Then a funny thing happened. Some of my patients who had failed to benefit from my traditional orthopedic surgical approach received some injections of proliferant solution. These made them better. I thought it must be a hoax or a placebo effect. Nonetheless, since I did not understand the material being injected, I had to investigate it further. To my surprise, a prospective scientific study on prolotherapy was about to be initiated in Santa Barbara, California. I was asked to monitor the study to vouch for the methods and result. I actually took on this role with the confidence that my scientific integrity would be able to squash this "hokey" concept of sclerosant injection into ligaments once and for all. I had heard of it, of course; the same concept had worked for the old-time vascular surgeons. However, none of my professors had ever talked about it, and I had never seen an exhibit at an academy meeting about it. What reason was there to believe it worked? But, I wondered, could it work? Thus, I became involved with a prospective randomized double- blind study in Santa Barbara in otherwise healthy people with chronic back and pelvis pain.  This was the best clinical study in which I had ever been involved. To rule out all placebo effect, the results of this prospective study were not evaluated until 6 months after the completion of treatment. The study was described by the editor of the journal Spine as an "elegant study." It clearly documented the benefits of prolotherapy over injection of local anesthesia. The editors of Spine, however, said they could not publish it, because they did not like the results! Although I was one of the founding editors of Spine, I resigned, and the paper was published elsewhere.
This short story underscores the bias in the scientific community against innovative concepts that, by the nature of the tissue being evaluated in treatment, have poor capacity for objective measurement. Good clinical studies are expensive. The small 95-subject Santa Barbara project cost hundreds of thousands of dollars that were provided by a private foundation. A prodigious amount of donated time was necessary to complete it. Can you imagine the government funding a prolotherapy study? 
This approach is safe, works well in appropriate patients, and should be part of the health care system of clinicians interested in comprehensive care of patients. It is also inexpensive. Perhaps, in this era of cost concern, its time has arrived. 
REFERENCES   l. Klein RG, Eek BC, DeLong WB, Mooney V: A randomized double-blind trial of dextrose-glycerin-phenol injections for chronic low back pain. J Spinal Disord 6:23-33, 1993.  
This is the American Association of Orthopedic Medicine’s comment on prolotherapy for low back pain http://www.aaomed.org/prolotherapy-back-pain

Ongley M, Klein R, Dorman T, et al: A new approach to the treatment of chronic low back pain. Lancet 1987;2:143-146.
This was the first double-blind trial of prolotherapy. The patients averaged 10 years of chronic low back pain. 35 of 40 (ie88%) of the treatment group had greater than 50% improvement in disability scores compared with 16 of 41 (39%) in the control group.

Klein R, Eek BC, DeLong B, et al: A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic low back pain. J Spinal Disord 1993; 6:23-33.
This second double-blind trial found 77% of the experimental group got more than 50% improvement in pain or disability scores compared to 52% in the lignocaine-only group.

Klein R, Dorman TA, Johnson: Proliferant injections for low back pain: Histological changes of injected ligaments & objective measurements of lumbar spine mobility before & after treatment: J Neurol & Orthop Med & Surg 1989; 10:123-126.
Biopsies of 3 patients’ sacro-iliac ligaments before and after prolotherapy showed and average increase in collagen fibre diameter from 0.055 to 0.087 micrometres. There was also significant increase in range of motion, and decrease in pain visual analogue scale and disability score.

Dorman TA et al, Energy efficiency during human walking before and after prolotherapy. J Orthopaed Med 1995; 17:24-26. Using oxygen consumption as a measure of energy expenditure, 9 patients with low back pain were assessed before and after prolotherapy. All patients were substantially improved symptomatically and 7 of the 9 were able to walk faster and consumed less oxygen even at the new faster walking speed

Dechow E, Davies RK, Carr AJ, Thompson PW. A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatology (Oxford). 1999;38:1255-9. This negative trial used only 3 treatments - not enough for chronic low back pain.

Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician 2006 9:115-121 AND
Klein RG, Eek B, O'Neill C, Elin C, Mooney V. Biochemical injection treatment for discogenic low back pain. A pilot study. Spine J;3(3): 220-226

These 2 studies used radiological imaging to inject discs with prolotherapy solutions. 57% of the patients in the second study had greater than 50% improvement in pain and disability.

Wilkinson HA, Injection therapy for enthesopathies causing axial spine pain and the "failed back syndrome": a single blinded, randomized and cross-over study. Pain Physician. 2005 Apr;8(2):167-73  - 80% good to excellent relief of pain after glucose/phenol/glycerine prolotherapy injection vs 47% after anaesthetic alone. However the single injection lasted, on average, only 2 months. These 35 were all scheduled for surgery, and only 4 eventually needed it.

Chakraverty R, Dias R. Audit of conservative management of chronic low back pain in a secondary care setting--part I: facet joint and sacroiliac joint interventions. Acupunct Med. 2004 Dec;22(4):207-13
63%of 19 patients undergoing prolotherapy for sacroiliac joint pain had improved at six months, compared to 33% of 33 who had intra-articular corticosteroid.

Hooper RA, Ding M, Retrospective case series on patients with chronic spinal pain treated with dextrose prolotherapy. J Altern Complement Med 2004; 10(4):670-4.
91% of patients - less pain; 85% of patients - improvement in activities of daily living, and 84% - improvement in ability to work. Women required on average, three more injections than men. Cervical spine response rates were lower than thoracic or lumbar spine.

Kim WM, Lee HG, Jeong CW, Kim CM, Yoon MH.A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J Altern Complement Med. 2010 Dec;16(12):1285-90. This Korean pain clinic trial compared 3 biweekly injections of steroid and glucose prolotherapy. At 2 weeks there was no difference, but at 15 months, 59% of the prolotherapy group had >50% pain relief compared with 10% of the steroid group, a significant difference.


Grote W, Delucia R, Waxman R, Zgierska A, Wilson J, Rabago D. Repair of a complete anterior cruciate tear using prolotherapy: a case report. Int Musculoskelet Med. 2009 Dec 1;31(4):159-165. This partial/complete tear on MRI in an 18 year old skiier responded fully to 7 prolotherapy sessions and exercise.
Reeves KD, Hassanein K: Randomised, prospective double-blind, placebo controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Evidence of pain improvement, range of motion increase, reduction of ACL laxity, and early evidence for radiographic stabilization. Altern Ther Health Med 2000; 6:68-74, 77-80. This DB trial used a non-inflammatory 10% glucose solution and they still found 40% decrease in pain, 63% decrease in swelling and 14% increase in flexion by 12 months.
Ongley M, Dorman TA et al: Ligament instability of knees: A new approach to treatment. Manual Med 1988; 3
Five patients with severe and reproducible ligament instability were treated and assessed with a Genucom computerized electrogoniometer. After the anterior and posterior cruciate ligaments were injected there were measurable improvements and anterior displacement and ability to ride bicycles etc.
Reeves KD and Hassanein K, Long term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med, 2003;9(3):52-56.  10 of 16 knees were measurably normal by 3 years and 9 were normal by 12 months. See this study on his website www.drreevesonline.com

Rabago D et al. Ann Fam Med. 2013 May-Jun;11(3):229-37 Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial.

In this trial 90 people had 3 or more prolotherapy or saline treatments and were assessed after 52 weeks. WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively)

SolmazI, AnesthPain Med. 2013 Dec 16;4(1):e9171 In this case study, a 72 yr old woman with severe knee pain for over 5 years had grade 4 (severe) osteoarthritis of a knee. A year after 6 prolotherapy treatments the pain was significantly reduced and the xray changes were reduced to grade 1 - the pictures are worth going to PubMed to see


Neck Disability Index (NDI) was 24.7 and decreased to 14.2 (at 2 months), 13.4 (at 6 months) and 10.9 (at 12 months). Average decrease 13.77 (p<0.0001) by 12 months. Motor vehicle litigation was not a barrier to recovery.
Centeno CJ, Elliott J, Elkins WL, Freeman M
Dorman TA, Whiplash injuries: treatment with prolotherapy and a new hypothesis. J Orthopaed Med
1999; 21:13-21. Retrospective analysis of 45 patients for decrease in pain and improvement in daily
living activities. Includes a detailed description of his method. All the patients in the right of the diagram
have improvements in VAS from 5-10 down to 1-6, for example you can see there are 8
patients whose pain dropped from 10 to 2
                                                          pain after treatment
    pain before treatment   


Reeves KD & Hassanein K: Randomised, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J of Altern Complementary Med 2000;6(4):311-320. 42% improvement in pain in the dextrose group compared with 15% in the placebo group. Movement also was significantly improved.


Chakraverty RC, A case of osteitis pubis secondary to unilateral sacroiliac joint instability treated with prolotherapy. J Orthopaed Med 2003;25:10-13

Healing of many tendon problems (eg Achilles, patella, elbow etc) is inhibited by VEGF produced in neovessels around the tendon. Hypertonic glucose is as effective as more expensive injections (polidocanol) or more effective, according to recent work published by John Lyftogt in Australasian Musculoskeletal Medicine, Nov 2007. The injections are more effective if subcutaneous than if injected into the tendon and much less painful.

Reeves KD, Treatment of consecutive severe fibromyalgia patients with prolotherapy. J Orthopaed Med 1994;16: 84-89 31 patients treated with prolotherapy to multiple tender points - many had significant improvement, some to no pain.

Dorman TA, Prolotherapy: A Survey. J Orthopaedic Med 1993;15:49. Very few complications in nearly half a million treatments.
Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL, Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: A survey of practitioners. Arch Phys Med Rehabil. 2006 Jul;87(7):909-13

Dorman TA and Ravin TM: Diagnosis and Injection Techniques in Orthopedic Medicine, 1991 pub Williams & Wilkins. An excellent textbook of Orthopedic Medicine which includes prolotherapy techniques. No longer available easily
Hackett G, Hemwall and Montgomery: Ligament and Tendon Relaxation Treated by Prolotherapy 1991 The pioneering textbook by Hackett, revised by Hemwall. Available from Hackett Hemwall Foundation, US $100 hard cover, US$75 soft cover. To pay from overseas email [email protected] before ordering.


Ravin, Cantieri and Pasquarello, Principles of Prolotherapy. From www.principlesofprolotherapy.com US$300

Ross Hauser's website has many useful articles and books for non-medical people
The American Association of Orthopedic Medicine website has articles by some of the leaders in prolotherapy in the USA.



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