Prolotherapy: A Literature Review and Retrospective Study
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
The Journal of Neurological and Orthopadic Medicine and Surgery, Vol. 12. No. 3. 1991
Robert G. Schwartz, M.D. and Noreen Sagedy, M.D.
Abstract. Proliferative therapy (prolotherapy) is the process whereby dextrose, P25G or sodium morrhuate is injected into ligaments in order to produce a proliferating response of that ligament. The purpose of these injections is to strengthen ligamentous structures and relieve pain. A review of the literature is provided and a retrospective study presented which demonstrates a 66% redction of sacroiliac low back pain in two-thirds of the patients who received this form of treatment.
Key Words: Prolotherapy – Scierotherapy – Low Back Pain – Sacroiliac pain.
Ligaments consist of many strands of fibrous tissue which may run parallel or crisscross at various angles to each other. They provide stabilization of joints in all positions. Pain occurs when normal tension on a ligament stretches the fibers. This results in stimulation of the sensory fibers which do not stretch along with the ligament (1). In sprain or tearing, the fibers become separated from bone, and tthere is an accumulation of lymphy or blood at the site of injury. Healing occurs through initiation of the wound response cascade mediated by chemotactic agents and inflammatory cells. Fibrin is produced and develops into a permanent strong fibrous tissue attached to bone.
There is also a production of bone at the enthesis (1). The healing process can be interfered with. Subsequent activity can cause separation, or the repair capacity in the individual can be deficient. This results in ligament relaxation which is a weakness of the attachment. If this remains, predisposition to repeat injury, chronic pain, and altered range of motion can persist (1,2).
The healing process can be stimulated by the infiltration of a proliferative solution within the ligament. Thus, the development of firm permanent fibrous tissue with reduction of pain can take place (1-8).
Literature Review
The rich supply of nerve endings in articular ligaments was first described by Lerich in 1930 and later by Gardner in 1953. Hackett described most joint pain as ligament pain. He was the first to scientifically demonstrate a method of strengthening ligaments by the injection of a proliferative solution. Inflammation was produced and a permanent increase in ligament size by 35-40% resulted.
Hackett claimed a cure rate of 82% in 1600 patients with low back pain (1). At this time, proliferative therapy was know as sclerotherapy. This was because the irritants used in prolotherapy were thught to work by creation of scar tissue rather than by the development of proliferative response. Tome of the irritants used in prolotherapy had been used to sclerose varicose veins as well (5).
A 1982 study by Li et al. quantified biochemically in a double-blind study the influence of injecting a proliferative solution (100ml of 5% sodium morrhuate) into rabbit medical collateral ligaments in situ. Results revealed a highly signigicant increase of the ligament’s mass, thickness, enthesis strength, and its weight/length ratio in comparison with the saline injected controls (9).
A 1985 study, also using 5% sodium morrhuate, was conducted by Maynard et al. They did a series of five 100ml injections into intact rabbit patellar tendons and Achilles tendon. This study showed that not only is there an increase in the number of cells but also a wider variety of cell types, including fibroblast, neutrophils, lymphocytes, plasma cells, and unidentifiable cells in the injected tissues. An increase in water content and amino sugar content were also noted. Interestingly, a decrease in the mean collagen fibril diameter and hydroxyproline content were documented despite an overall increase in fibrin mass (10).
In 1987, a double – blind study was done by Ongley et al. compaing 40 patients who received spinal manipulations and ligament strengthening proliferative therapy with 41 patients who received minor manipulations and 0.9% saline injections. One injection per week was done for 6 weeks. The solution used was 2.5%phenal/25% dextrose/25% glycerin/47.5% pyrogen free water (P25G).
At 6 months following the endof the treatments, 35 patients in the experimental group reported greater than 50% improvement compared with only 16 in the control group. Furthermore, 15 patients in the experimental group were disability-free compared with 4 patients of the control group reporting no disability (3).
In a different study by R.G. Klein in 1989 histologic documentation of ligament proliferation in human subjects in response to proliferative injections was demonstrated. Biopsy specimens of posterior sacroiliacligaments were performed pre- and posttreatment in three patients with low back pain. Each patient received a series of six weekly injections using the P25G solution into the sacroiliac ligaments. The proliferative injections resulted in collagen of objectively increased diameter and was associated with decreased pain along with an objective increase in range of motion (4).
Biochemical Basis
The healing of a wound has been divided into three phases: (1) inflammatory (early and late), (2) granulation tissue formation, and (3) matrix formation and remodeling (11). Inflammation is the reaction of living tissues to all forms of injury. It involves vascular, neurologic, humoral, and cellular responses at the site of injury. Increased vascular permeability is the first mechanism. It allows the escape of plasma proteins and white cells. This is known as exudation. Neutrophils appear in perivascular spaces and they are followed by monocytes/macrophages (11).
The most important chemotactic factors for both neutrophils and macrophages include C5a, a compnent of the complement system, leukotriene B4, a product of arachidonic acid metabolism, and bacterial products. Macrophages are also attracted by the basic peptides in the lysosomal granules of neutrophils and this explains why they appear as the second line of defense. These cells then destroy or neutralize the injurious agent by phagocytosis allowing for the repair of the damaged site to then occur (12).
Repair is the process by which lost or destroyed cells are replaced by new, living cells. The tissue defect is initially filled up with highly vascularized connective tissue called granulation tissue. It consists of newly formed small blood cells embedded in loose ground substance containing fibroblasts and inflammatory cells. Fibroblasts migrate into the wound bed under the influence of chemotactic factor (11,12).
As granulation tissue matures, inflammatory cells decrease in number, fibroblasts lay down collagen, and the capillaries become less prominent. An avascular, relatively acellular tissue with inactive spindle-shaped fbroblasts tucked in between collagen fibers emerges. The collagen fibers then aggregate into mature fibrils. The acquisition of tensile strength follows a sigmoid curve (12). The orderly movement and proliferation of cells within a healing wound is influenced by both cell signals and extracellular matrix (e.g., fibronectin and growth-stimulating factors). Thus, a wound-healing cascade is present. The growth associated with repair is regulated and ceases when healing is completed (12).
Proliferants are substances which cause a localized tissue reaction leading to an inflammatory response. The wound – healing cascade is thus triggered resulting in fibroplasia and collagen deposition. The healing cascade begins with granulocyte infiltration followed by monocyte/macrophage invasion. Growth factors are released and thus activated fibroblasts are recruited to the site to secrete new matrix. This new matrix includes collagen fibrils (2,6,7,13).
Any factor which leads to fibroplasia can be a proliferative. There are three categories of proliferants that have been used: irritants, osmotic shock agents, and chemotactic agents Irritants (e.g., phenol, quaicol, tannic acid, and quinine) create a local tissue reaction which causes granulocyte infiltration. Osmotic shock agents (e.g., glucose, glycerin, ZnSO4) creat a local tissue reaction to stimulate a granulocyte infiltration by dehydration. Dhemotactic agents (e.g., sodium morrhuate) cause direct activation of local inflammatory cells (13).
In some instances the injected factor is altered in vivo. Phenol oxidizes to reactive quinine and sodium morrhuate as an arachidonic acid compound is a precursor to many cytokines, including leukotrienes, thromboxanes, and prostaglandins (13). Growth factors are a fourth category currently being researched at Biogenteic Laboratories (e.g., EFG, PDGF, IFG-I, FGF, TGF-beta). They directly recruit and activate local fibroblasts (13).
Materials And Methods
The effects of prolotherapy on 43 patients with chronic sacroiliac strain were retrospectively reviewed. There were no sciatic tension signs, motor weakness, sensory deficits, or patients with bone abnormalities entered into the study. The patients had all failed to respond to other forms of treatment including surgery. Ages ranged from 20 to 70 years.
Treatment consisted of three injections into the insertion of the posterior sacroiliac ligament, beginning at its most caudal one-third and moving superiorly by one-third of its length with each injection (fig. 1) The injections were done 2 weeks apart. The proliferant used was a mixture of 1 cc of 5% sodium morrhuate and 1 cc of 1% Xylocaine. A needle of proper length was used that assured the proliferant was placed on bone. The solution was distributed throughout the fibro-osseous junction.
Each patient was informed that there would be a 2- to 3- day period of discomfort in the area of the injection due to the initiation of the wound-healing cascade. Instructions were given to avoid aspirin, ibuprofen, or other prostaglandin inhibitors, and to use only acetaminophen to relieve pain. Activity was encouraged. The patients were instructed in sacroiliac mobilization exercises and fitted with a sacroiliac belt.
Each patient was seen on 2-week follow-up after the third injection. Subjective percentages of relief were recorded. If satisfactory pain relief had been obtained, they were discharged from treatment and instructed to return on an as-needed basis.
Results
At the conclusion of the three injection series, on 2-week follow-up, 20/43 patients reported 95% improvement, 31/43 75% or better improvement, and 35/43 reported 66% or better improvement. Thus, 2/3 of the patients received 66% relief. No improvement was reported by 3/43. While no formal mechanism for prolonged follow-up was in place 10/40 or 25% reported some level of recurrence.
Discussion
The sacroiliac joint can be considered to be unstable when the ligaments are relaxed. Because of this joint’s weight-bearing spinal mechancis the ligaments supporting it frequently become damaged. This can lead to intense pain, which may become chronic. It can result in abnormal compensatory movement as well. The altered spinal kinesiology can lead to further injury of other structures such as lumbar vertbrae, sacrum, and intervertebral disks.
Prolotherapy treatment is designed to strengthen the sacroiliac ligaments so as to develop normal tension in them. Numbing of the ligament with Xylocaine and obtaining immediate relief provides for temporary comfort from the injection. The ensuing painful reaction that occurs from the proliferative injection represents the activity of the initiated wound-healing response. Prostaglandin inhibiting medications should be avoided.
It important to choose the proliferative solution wisely and to make sure the needle is on bone when injecting. Three cases of paralysis and two deaths have been documented after inadvertant injection of psyllium seed oit and zinc sulfate into the subarachnoid space (14-16).
Other investigators have used a phenol/dextrose/glycerin solution (P25G) and obtained significant results without complications. While the percentage of phenol in P25G is very dilute and probable safe, many clinicians prefer to use either dextrose or sodium morrhuate, as both of these agents have also been used intravenously for other medical conditions (8,17).
Prolotherapy treatment has been utilizedat other ligamentous structures in addition to the sacoiliac area. Intraspinous, ileolumbar, fibulocalcaneal, medial and lateral collateral (about the knee), radiohumeral, coracoclavicular, and sternoclavicular ligaments are frequent ligamentous injection sites. Intraarticular ligamentous injections have also been performed (2,7,8).
Although this study is a retrospective one, the data support the studies of Lui, Maynard, Ongley, and Klein. While we have not done biopsy studies to prove a proliferative effect occurred, we did obtain significant pain relief without any undue side effects (2,3,9,10).
Conclusion
We conclude from this study and the aforementioned literature that it is possible to induce proliferation of collagen in human ligaments using prolotherapy. The tissue that proliferates is a dense collagen and is associated with a reduction in pain. Mechanical back pain can be relieved by this method and other compensatory injuries prevented.
References
1. Hackett GS. Ligament and tendon relaxation treated by prolotherapy, 3rd ed. Springfield, Ill: Charles C. Thomas, 1958
2. Cyriax J. Textbook of orthopaedic medicine. Philadelphia: Bailliere Tindall, 1982
3. Onlgey MJ, Klein RG, Dorman TA, Eek BC, Hubert LJ. A New Approach to the Treatment of Chronic Low Back Pain. Lancet 1989; 11:143-146
4, Klein RG, Dorman TA Johnson CE. Proliferant injections for low back pain: histological changes of injected ligaments and objective measurements of lumbar spine mobility before and after reatment. J Neurol Orthop Med Surg 1989; 10:123-126
5, Injection therapy helps low back pain, study reveals. Back Pain Monitor 1988; 6:12:161-172
6. Gearhardt JJ. Interdisciplnary rehabilitation in trauma. Baltimore, Md: Williams and Wilkins, 1987
7. Mirman MJ. Sclerotherapy. Springfield, PA, 1986
8. Leedy RF. Basic techniques of sclerotherapy. Osteop Med 1987;9
9. Liu YK, Tipton CM, Matthes RD, Bedford TG, Maynard JA, Walmer WC. An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction
strength. Connect Tissue Res 1983; 11:95-102
10. Maynard JA, Pedrini VA, Pedrini-Mille A, Romanus B, Ohlerking F. Morphological and biochemical effects of sodium morrhuate on tendons. J Orthop Res 1985;3:236-248
11. Wyngarden JB. Cecil textbook of medicine. Philadelphia;W.B. Saunders, 1988
12. Robbins SL, Kumar V. Basic pathology, 4th ed. Philadelphia: W.B. Saunders, 1987
13. Banks A. Biochemical effects of prolotherapy. First Annual High Country Prolotherapy Workshop, Denver, Co., 1989
14. Hunt WE, Baird WC. Complications following injections of sclerosing agent to precipate fibro-osseouis proliferation. J Neurosurg 1961; 18:461-65
15. Keplinger JE, Bucy PC. Paraplegia from treatment with sclerosing agents-report a case.JAMA 1960: 73:1333-36.
16.Schneider RC, Williams JI, Liss L. Fatality after injection of sclerosing agent to precipitate fibro-osseous proliferation. JAMA 1960; 170:1768-1772
17. Lawson AW. Acute esophageal variceal sclerotherapy. JAMA 1986; 255:497-500
Fig. 1. Needle Location used for injection of the sacroiiac ligaments.
Trigger point of ligaments: (IL)
Iliolumbar: (LS) Lumbosacral-supra and interspinus: (A,B,C,D,) Posterior sacroiliac; (SS) Sacroapinus; (ST) Sacrotuberus;(SC) Sacrococcygeal;(H) Hip-Articular; (SN) Sciatic nerve (With permission from G.S. Hackett, Ligament and Tendon Relaxation. Charles C. Thomas Co., 1958)
Prolotherapy Peer-Reviewed and Scientific Articles and Abstracts Part 2
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity.
Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med 2000 Mar;6(2):68-74, 77-80.
CONTEXT: Use of prolotherapy (injection of growth factors or growth factor stimulators). OBJECTIVE: Determine the effects of dextrose prolotherapy on knee osteoarthritis with or without Anterior Cruciate Ligament (ACL) laxity.
DESIGN: Prospective randomized double-blind placebo-controlled trial. SETTING: Outpatient physical medicine clinic.
PATIENTS OR OTHER PARTICIPANTS: Six months or more of pain along with either grade 2 or more joint narrowing or grade 2 or more osteophytic change in any knee compartment. A total of 38 knees were completely void of cartilage radiographically in at least 1 compartment.
INTERVENTION: Three bimonthly injections of 9 cc of either 10% dextrose and .075% lidocaine in bacteriostatic water (active solution) versus an identical control solution absent 10% dextrose. The dextrose-treated joints then received 3 further bimonthly injections of 10% dextrose in open-label fashion. MAIN OUTCOME MEASURES: Visual analogue scale for pain and swelling, frequency of leg buckling, goniometrically measured flexion, radiographic measures of joint narrowing and osteophytosis, and KT1000-measured anterior displacement difference (ADD).
RESULTS: All knees: Hotelling multivariate analysis of paired observations between 0 and 6 months for pain, swelling, buckling episodes, and knee flexion range revealed significantly more benefit from the dextrose injection (P = .015). By 12 months (6 injections) the dextrose-treated knees improved in pain (44% decrease), swelling complaints (63% decrease), knee buckling frequency (85% decrease), and in flexion range (14 degree increase). Analysis of blinded radiographic readings of 0- and 12-month films revealed stability of all radiographic variables except for 2 variables which improved with statistical significance. (Lateral patellofemoral cartilage thickness [P = .019] and distal femur width in mm [P = .021]. Knees with ACL laxity: 6-month (3 injection) data revealed no significant improvement. However, Hotelling multivariate analysis of paired values at 0 and 12 months for pain, swelling, joint flexion, and joint laxity in the dextrose-treated knees, revealed a statistically significant improvement (P = .021). Individual paired t tests indicated that blinded measurement of goniometric knee flexion range improved by 12.8 degrees (P = .005), and ADD improved by 57% (P = .025). Eight out of 13 dextrose-treated knees with ACL laxity were no longer lax at the conclusion of 1 year.
CONCLUSION: Prolotherapy Injections with 10% dextrose resulted in clinically and statistically significant improvements in knee osteoarthritis. Preliminary blinded radiographic readings (1-year films, with 3-year total follow-up period planned) demonstrated improvement in several measures of osteoarthritis severity. ACL laxity, when present in these osteoarthritic patients, improved.
Long-term effects of dextrose prolotherapy injections for anterior cruciate ligament laxity
Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med. 2003 May-Jun;9(3):58-62.
CONTEXT: Use of dextrose prolotherapy. Prolotherapy is defined as injection that causes growth of normal cells or tissue.
OBJECTIVE: Determine the 1 and 3 year efficacy of dextrose injection prolotherapy on anterior cruciate ligament (ACL) laxity. After year 1, determine patient tolerance of a stronger dextrose concentration (25% versus 10%).
DESIGN: Prospective consecutive patient trial. SETTING: Outpatient physical medicine clinic. PATIENTS OR
OTHER PARTICIPANTS: Eighteen patients with 6 months or more of knee pain plus ACL knee laxity. This laxity was defined by a KT1000 anterior displacement difference (ADD) of 2 mm or more.
INTERVENTION: Intraarticular injection of 6-9 cc of 10% dextrose at months 0, 2, 4, 6, and 10. Injection with 6 cc of 25% dextrose at 12 months. Then, depending on patient preference, injection of either 10% or 25% dextrose every 2-4 months (based on patient preference) through 36 months.
MAIN OUTCOME MEASURES: Visual analogue scale (VAS) for pain at rest, pain on level surfaces, pain on stairs, and swelling. Goniometric flexion range of motion, and KT1000-measured ADD were also measured. All measurements were obtained at 0, 6, 12 and 36 months.
RESULTS: Two patients did not reach 6 month data collection, 1 of whom was diagnosed with disseminated cancer. The second was wheelchair-bound and found long-distance travel to the clinic problematic. Sixteen subjects were available for data analysis. KT1000 ADD, measurement indicated that 6 knees measured as normal (not loose) after 6 months, 9 measured as normal after 1 year (6 injections), and 10 measured as normal at 3 years. At the 3 year follow-up, pain at rest, pain with walking, and pain with stair use had improved by 45%, 43%, and 35% respectively. Individual paired t tests indicated subjective swelling improved 63% (P = .017), flexion range of motion improved by 10.5 degrees (P = .002), and KT1000 ADD improved by 71% (P = .002). Eleven out of 16 patients preferred 10% dextrose injection.
CONCLUSION: In patients with symptomatic anterior cruciate ligament laxity, intermittent dextrose injection resulted in clinically and statistically significant improvement in ACL laxity, pain, swelling, and knee range of motion.
Prolotherapy Peer-Reviewed and Scientific Articles and Abstracts
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
The Medical Rationale for Prolotherapy
Millions of Prolotherapy injections are given each year. But does it work? Numerous articles have been published, (some of the more important ones are listed below) to determine just that. Is Prolotherapy a placebo? According to the published research, Prolotherapy is not a placebo, Prolotherapy stimulates healing.
Scientific and medical papers
Banks, AR. A Rationale for Prolotherapy, J Orthopedic Medicine, 1991;13:55-59.
Hackett GS, Henderson DG. Joint stabilization: An experimental, histologic study with comments on the clinical application in ligament proliferation. Amer J Surg 1955;89:968-973.
Hackett GS. Referred pain and sciatica in diagnosis of low back disabilities, JAMA 1957;63:183-185.
Hauser RA. Punishing the pain. Treating chronic pain with Prolotherapy. Rehab Manag. 1999;12(2):26-28, 30.
Klein R, Dorman T, Johnson C. Proliferant injections for low back pain: histologic changes of injected ligaments and objective measurements of lumbar spinal mobility before and after treatment. J Neurologic and Orthopedic Medicine and Surgery. 1989;10:123-126.
Klein R, Eek B, DeLong B, Mooney V. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord. 1993;6:23-33.
Klein R, Eek B. Prolotherapy: an alternative approach to managing low back pain. J Musculoskeletal Medicine, 1997;May:45-49.
Liu Y, Tipton C, Matthes R, Bedford T, Maynard J, Walmer H. An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Connect Tissue Res. 1983;11:95-102.
Maynard J, Pedrini V, Pedrini-Mille A, Romanus B, Ohlerking F. Morphological and biochemical effects of sodium morrhuate on tendons. Journal of Orthopedic Research. 1985;3:236-248.
Ongley M, Dorman T, et al. Ligament instability of knees: a new approach to treatment. Manual Medicine 1988;3:152- 154.
Ongley M, Klein R, Dorman T, Eek B, Hubert L. A New Approach to the Treatment of Chronic Low Back Pain. Lancet 1987;2:143-146.
Reeves KD, et al. Randomized, prospective, placebo-controlled double-blind study on dextrose prolotherapy for osteoarthritic thumb and finger (dip, pip, and trapeziometacarpal) joints: evidence of clinical efficacy. The Journal of Alternative and Complementary Medicine. 2000;6(4):311-320.
Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med 2000 Mar;6(2):68-74, 77-80.
A systematic review of prolotherapy for chronic musculoskeletal pain.
Rabago D, Best TM, Beamsley M, Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med. 2005 Sep;15(5):376-80.
OBJECTIVE: Prolotherapy, an injection-based treatment of chronic musculoskeletal pain, has grown in popularity and has received significant recent attention. The objective of this review is to determine the effectiveness of prolotherapy for treatment of chronic musculoskeletal pain. DATA SOURCES: We searched Medline, PreMedline, Embase, CINAHL, and Allied and Complementary Medicine with search strategies using all current and historical names for prolotherapy and injectants. Reference sections of included articles were scanned, and content area specialists were consulted. STUDY SELECTION: All published studies involving human subjects and assessing prolotherapy were included. MAIN RESULTS: Data from 34 case reports and case series and 2 nonrandomized controlled trials suggest prolotherapy is efficacious for many musculoskeletal conditions. However, results from 6 randomized controlled trials (RCTs) are conflicting. Two RCTs on osteoarthritis reported decreased pain, increased range of motion, and increased patellofemoral cartilage thickness after prolotherapy. Two RCTs on low back pain reported significant improvements in pain and disability compared with control subjects, whereas 2 did not. All studies had significant methodological limitations.
CONCLUSIONS: There are limited high-quality data supporting the use of prolotherapy in the treatment of musculoskeletal pain or sport-related soft tissue injuries. Positive results compared with controls have been reported in nonrandomized and randomized controlled trials. Further investigation with high-quality randomized controlled trials with noninjection control arms in studies specific to sport-related and musculoskeletal conditions is necessary to determine the efficacy of prolotherapy.
TemporoMandibular Joints (TMJ)
Hakala RV. Prolotherapy (proliferation therapy) in the treatment of TMD.
Cranio. 2005 Oct;23(4):283-8.
Proliferation therapy, or “prolotherapy,” is also known as regenerative injection therapy (RIT). Since the 1930s, the technique has been used to stabilize injured joints and to relieve joint pain. This article reviews the history and scientific literature regarding prolotherapy and describes the application of the technique to treat injured or unstable temporomandibular joints (TMJ). Alternative medicaments and the likely mechanisms of action are discussed. A brief preliminary summary of a retrospective clinical study of the efficacy of prolotherapy is included. The study shows that prolotherapy can be an effective therapeutic modality that reduces TMJ pain and joint noise in a majority of patients who have reached a plateau with use of an intraoral appliance, physical therapy, and home care.
The use of therapeutic medications for soft-tissue injuries in sports medicine.
Paoloni JA, Orchard JW. The use of therapeutic medications for soft-tissue injuries in sports medicine. Med J Aust. 2005 Oct 3;183(7):384-8.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) to treat most muscle, ligament and tendon injuries should be reassessed. They have, at best, a mild effect on relieving symptoms and are potentially deleterious to tissue healing. Soft-tissue injury associated with definite inflammatory conditions such as bursitis or synovitis or involving nerve impingement does warrant short-term treatment with NSAIDs. Paracetamol has similar efficacy to NSAIDs in soft-tissue injury, is cheaper, and has a lower side-effect profile. It is the analgesic of choice for most soft-tissue injury. Cyclo-oxygenase-2 (COX-2) inhibitors should not be used to treat soft-tissue injuries unless impingement is a major feature and non-selective NSAIDs are contraindicated (eg, coexisting gastric disorder), and the patient is not at cardiovascular risk. Corticosteroid injections for tendon injuries may achieve a mild to moderate reduction in pain for up to 6 weeks. However, they do not promote tendon healing, so should generally be used only when healing is not a critical goal. Promising new therapeutic treatments for soft-tissue injuries include topical glyceryl trinitrate, aprotinin injections, and prolotherapy.
Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature.
Dagenais S, Haldeman S, Wooley JR. Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature. Spine J. 2005 May-Jun;5(3):310-28.
BACKGROUND CONTEXT: The injection of various solutions aimed at producing a sclerosing effect has been used to treat soft tissues injuries (eg, inguinal hernia) for more than 100 years. In the 1930s, this treatment approach was applied to injured joints in an attempt to stimulate connective tissue repair. Although several studies have been published about this method of treatment for various orthopedic and spinal indications (termed prolotherapy), its use remains controversial.
PURPOSE: To conduct a critical review of the literature on prolotherapy for spinal pain. STUDY DESIGN/SETTING: Critical review of the literature. METHODS: Computerized medical literature databases (Medline, CINAHL, Mantis, Cochrane Central Register of Controlled Trials) were searched to uncover all published information about the use of sclerosing injections in humans with spinal pain disorders. Search results were reviewed for relevance, and information was abstracted from full-text articles. RESULTS: Our search uncovered almost 200 reference materials in various media related to prolotherapy, including 31 clinical studies related to spinal pain. There were 26 observational cohorts and 5 randomized clinical trials (RCTs). Indications in these studies were low back pain (22), neck pain (3), cervical headaches (3) and dorsal or thoracic pain (3). A total of 20 sclerosing solutions were used in these studies; the most common was a mixture of dextrose 12.5%, glycerin 12.5%, phenol 1.25% and lidocaine 0.25%. Wide variations were found in treatment protocols, such as dose, number of treatments and use of adjunct therapies. Most cohort studies were only of moderate quality and varied greatly in the substances injected and the use of co-interventions. Most clinical studies reported positive results such as decreased pain or disability, although differences between treatment and control groups did not always reach statistical significance. Commonly reported adverse reactions to this treatment include temporary postinjection pain and stiffness. A handful of more serious adverse events were reported in the 1950s and 1960s with stronger or unknown solutions.
CONCLUSION: Prolotherapy describes a variety of treatment approaches rather than a specific protocol. Results from clinical studies published to date indicate that it may be effective at reducing spinal pain. Great variation was found in the injection and treatment protocols used in these studies that preclude definite conclusions. Future research should focus on those solutions and protocols that are most commonly used in clinical practice and have been used in trials reporting effectiveness to help determine which patients, if any, are most likely to benefit from this treatment.
Prolotherapy Treatment of Low Back Pain and Scaitica
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
Presented at the 1960 Annual Alumni Meeting Hospital for Joint Diseases
BULLETIN OF THE HOSPITAL FOR JOINT DISEASES Volume XXII, No. 1, April 1961
Abraham Meyers, M.D.
PROLOTHERAPY IS the treatment of relaxed ligaments by the injection of sclerosing agents into the ligaments and tendons. This sets up a proliferative reaction which follows the laws of inflammation the end result of which is the formation of fibrous connective tissue. The application of Prolotherapy to treatment of low back pain and sciatica is derived from the work of Leriche and Steindler. Leriche’s (1) studies revealed the rich supply of sensory nerve endings in articular ligaments and advocated the infiltration of these ligaments with local anesthetics for the relief of pain after sprains and fractures. The studies of Steindler and Luck (2), (1925 and 1938) indicated that irritation of ligaments of the lumbosacral region may act as trigger points resulting in local pain and in secondary conducted pain to specific dermatome or areas in the lower extremities. Infiltration of these regions with a local anesthetic, abolishes both the local and referred pain. Hackett (3), Baer (4), Steinbrocher (5), Travel and Travel (6), confirmed the above work and concluded that both the local and referred pain has its origin within the ligaments.
In the low back as in other joints, injured ligaments heal by scar tissue formation. In unprotected cases or where healing power is poor, lengthening of the ligaments results. Lengthening permits an abnormal range of movement in the joints which in turn stretches the inelastic nerve fibers contained in the ligaments causing local and referred or conducted pain.
The knowledge of the histology of tissue reactions following the use of proliferating solutions dates back to the Civil War Period when these solutions were used in the treatment of hernias. Rice, C.O. and Aratson (7) studied the histologic changes in the tissues of man and animals following injection of irritating solutions in the cure of hernia in 1936. They in turn refer to surgical articles written in 1832 by Janes (8) on the histology of these reactions. Rice indicates that fibrosis begins fifteen hours after injection of sclerosing solution into the tissues. The fibrous tissue is firm by seven days and progresses to adult compact bundles in eighteen days. Hackett (3) corroborates these findings and indicates that this tissue formation is permanent and rearrangement to tendinous and ligamentous structure occurs and that Prolotherapy results in stabilization of unstable joints. Alpers (9) (1953) on the problem of sciatica states that “herniated disc is preceded by relaxation of the spinal ligaments.”
Steindler (10) (1959) states that “Stabilization is indicated in treatment of cases of lumbosacral and sacroiliac pain and that the method of Hackett of causing a sclerosis of chronically relaxed ligaments of the back by injection is new and seems to recommend itself for its simplicity. Its purpose is stabilization by sclerosing the relaxed ligaments, the method is thus competitive to spinal fusion over which it has the advantage of simplicity.”
The rationale of the Prolotherapy treatment of low back pain and sciatica is based on the traditional orthopedic principle of stabilization of weakened joints and ligaments. Hackett (3) directs attention to the “ligaments” as being the cause of joint pain. As stated by Hackett, “joint pain is ligament pain. Hackett, Gormley (11) and Steindler (10) recall that the sacroiliac joint is frequently the site of low back pain and regret the recent tendency to forget it. Their statistics indicate that 58.5 % of low back pain is sacroiliac and 36.5 is lumbosacral and 5 % were combined. No controversy is intended against the treatment of extruded or protruded herniated discs by laminectomy and spine fusion. Many cases of disc syndrome respond to treatment by Prolotherapy and the selection of cases requiring surgery is facilitated by excluding sciaticas resulting from relaxed ligaments. The lower extremity pain resulting from nerve root pressure or referred pain from painful ligaments is similar. The lumbar and pelvic articular ligaments may be accompanied by sciatic pain on stretching as in the Lasague test, loss of ankle and knee reflexes, atrophy of the thigh and calf muscles and sciatic scoliosis or body list. Differential diagnosis is aided by identifying trigger point tenderness of the posterior sacroiliac, sacrotuberous and sacrospinous ligaments by finger point pressure or by needling.
My report is based on the treatment of 267 private cases of low back pain with or without sciatica from May 1956 to October, 1960. These are the problem type cases which are presented to the orthopedist most of which have not responded to or which have recurred after routine orthopedic treatment. Self limiting cases are excluded and Prolotherapy is not instituted unless pain persists for more than 4 to 6 weeks. Many have refused surgery or wish to try one more non-operative form of therapy before submitting to surgery.
For this discussion, the classification of low back pain and sciatica is simplified into two groups. 1. Acute trauma. 2. Unstable backs. The unstable back group includes cases of herniated discs, acute or degenerative osteoarthritic spines, spondylolisthesis, anomalous facets and sacralized transverse processes. Response to treatment is satisfactory in post-operative laminectomy and fusion; when the x-ray reveals arthritis, or congenital or acquired deformities; degenerative displacements and disc narrowing.
Fig. 1.
LS, lumbosacral; IL, ilio lumbar; A&B, high sacro-iliac; C&D, low sacroiliac; SC, sacrococcygeal; SS, sacro-sciatic; ST, sacro-tuberous; H, posterior capsule of hip joint; SN, sciatic nerve; on the right, ligaments are illustrated.
On the left, sites of injection are numbered.
Exact knowledge of the anatomy of the ligaments of the lumbosacral and sacroiliac areas is necessary. Figure 1 indicates the lumbosacral, iliolumbar, the high and low sacroiliac ligaments, the sacro-sciatic, sacrotuberous and sacro-coccygeal ligaments. They are labeled, LS, IL, A, B, C, D, SS, ST, SC, and H. The points of insertion of the needle for distribution of the sclerosing solution is also indicated.
FIG. 2
After the point of insertion of the needle is selected, the bony prominence is outlined by the fingers as illustrated in Figure 2, the soft tissues are depressed and retracted to make the bone more prominent and the needle then inserted between the fingers as a guide until the needle point touches bone. “Always touching bone” is important and prevents injection in a manner which will cause complications. With the needle on bone and with forced aspiration prior to injection, it is unlikely that a nerve root or blood vessel will be entered or that the needle or solution will be injected into the subarachnoid space or epidural space. One cc of solution is injected and the needle is then withdrawn, advanced subcutaneously, always against another portion of bone where additional one cc is deposited. The entire length of the insertion of the ligament under treatment is reached through one skin puncture.
FIG. 3
Figure 3 indicates the needle being placed through the supraspinous and interspinal ligaments of the lumbar area and adjacent to the spinous process, injecting the fibro-osseous junction where the tendon inserts into the bone.
FIG. 4
Figure 4 indicates this treatment being directed to the sacroiliac joint area inclining the needle away from the mid-line, touching bone in the depth of the sacroiliac ligaments. One should note the CD, SS area along the edge of the sacrum and distal to the notch of the posterior inferior spine of the ilium: This region is responsible for much of the referred or conducted sciatic pain in the sciatic distribution since it is adjacent to the Pyriformis muscle and related to the sciatic nerve.
FIG. 5
Figure 5 indicates the topographical anatomy comparable to the ligaments to be treated. It indicates the depression between L-a, S-1, A, the crest of the ilium, B, the notch below the inferior spine, the horizontal cross mark at the sacrococcygeal region, C, the hip joint area.
FIG. 6
Figure 6 illustrates the areas of referred pain comparable to the relaxed ligaments of the lumbosacral, sacroiliac areas worked out by Hackett (3). The referred pain pattern is characteristic and if carefully studied, the involved ligaments may be predicted from the patient’s description of the location of the pain in the buttocks and lower extremities.
In treating these 267 patients, over 4500 injections have been given without the occurrence of any complications. There has been no shock, no paralysis, no embolic formation and there has been no sloughing of tissues. Following the injections, there is post-injection pain of varying intensity. Some patients suffer very intense pain while others who have higher pain thresholds are hardly disturbed. It is well to advise that there will be severe pain and to furnish large doses of Demerol and Phenergan.
Injections are made at weekly intervals until all the ligaments are injected, doing as many as the patient permits or the operator feels he can tolerate. I usually give no pre-injection preparation but at times if the patient is accompanied may give an intramuscular injection of narcotic to facilitate more numerous injections. I now spray Ethyl Chloride at the site of injection. From 3 to 6 visits completes the series, a rest period of 6 to 8 weeks is suggested and then monthly follow-up visits or return visits for recurrences. Although one can inject specific ligaments if indicated, I have been injecting the entire low back area, mid-line L-3,L-4,L-5 transverse and facets, ligaments, iliolumbar, high and low sacroiliac, sacrosciatic, sacrotuberous ligaments in most patients. I have not found it necessary to resort to the use of traction since using Prolotherapy (1956). After 6 to 8 weeks, therapeutic exercises are started.
There are two solutions of choice, either a combination of l: Sylnasol to 3: Pontocaine solution; or a solution of zinc and Phenol. I have eliminated Phenol because of its toxicity. I have used zinc but find that there is severe prolonged pain following the zinc solution and have limited myself principally to the Sylnasol-Pontocaine solution. Since this work has been performed a dextrose-Phenol solution is being used which is almost painless.
I have treated 100 cases in the hospital under intravenous Pentothal anesthesia and feel that this is the preferred method of treatment. Treatment is completed at one time thereby eliminating the possibility that the series will be incomplete. A greater volume of sclerosing solution is injected and the sclerosing effect is better and severely incapacitated patients are quickly relieved of pain and disability. It was noted in the hospital cases that there was fever of one or two days duration following the injections probably on an allergic basis.
Dr. Hackett’s statistics indicate that 82 per cent of the patients were cured in a 19 year follow-up period. My percentages are similar although my follow-up period is shorter (1956 to November 1960).
Prolotherapy treatment of low back pain and sciatica is a rational method of stabilizing weak backs and it is complimentary to the conventional orthopedic methods of treatment. It is suggested that the two cases of unfortunate complications reported in the literature (12,13), should be carefully noted but not be permitted to discredit a valuable therapeutic method. Prolotherapy treatment of low back pain and relaxation of joint ligaments and tendons warrants further consideration by the orthopedic surgeon.
REFERENCES
1. LERICHE, R., GAZ. d. Hop. 103: 1294, 1930.2. STEINDLER, A. AND LUCK, J. V., Differential Diagnosis of Pain Low in the Back. J.A.M.A. 110: 106, 1938.
3. HACKETT, G. S., Ligament and Tendon Relaxation Treated by Prolotherapy. Charles C Thomas, Pub. 1956, 3rd Ed.
4. BAER, W. S.: Sacro-Iliac Strain. Bull. Johns Hopkins Hosp., 28: 159, 1917.
5. STEINBROCKER, O.: Analgesic Block in the Diagnosis and Treatment of Low-Back Pain. Curr. Researches in Anesth. & Analg., 20: 221, 1941.
6. TRAVELL, J., AND TRAVELL, W.: Therapy of Low Back Manipulation and of Referred Pain in the Lower Extremity by Procaine Infiltration. Arch. Phys. Med., 27: 537, 1946
7. RICE, C. O. AND ARATSON – Histologic Changes in the Tissue of Man and Animals Following the Injection of Irritating Solutions Intended for the Cure of Hernias. Ill. Med. J. 70: 271, Sept. 1936.
8. JANES, 1938 quoted by Rice, C. O.
9. ALPERS, B. J.: The Problem of Sciatica. Med. Cl. No. Am. 37: 503, 1953.
10. STEINDLER, A.: Interpretation of Pain in Orthopaedic Practice. Charles C. Thomas, Pub. 1959.
11. GHORMLEY, R. H.: Etiological Study of Backache and Sciatic Pain. Proc. Staff Meet. Mayo Clinic 26: 457, 1951.
12. SCHNEIDER, RICHARD C. M. D., WILLIAMS AND LISS: JAMA. 170: 1765, Aug. 8 1959.
13. COMBES, CLARR, GREGORY, JAMES: J.A.M.A. 173: 1336, July 23, 1960.
Injecting Relief Prolotherapy Can Effectively Reduce Chronic Pain Part 3
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
Part three of article segment Injecting Relief Prolotherapy Can Effectively Reduce Chronic Pain
The number of treatments and injections required per treatment are based on the type of injury. For example, two Prolotherapy treatments for patellofemoral syndrome of the knee (runner’s knee) will usually eliminate the pain. But for a more complex problem, such as bone-on-bone arthritis, it may take six to eight treatments over two months. Back and neck pain may call for a series of four to eight Prolotherapy Injections treatments overall.
Anti-inflammatory medications are contraindicated during Prolotherapy. And higher doses of NSAIDS, such as aspirin, ibuprofen, Celebrex or Vioxx, may inhibit the necessary inflammation and reduce the positive effects of Prolotherapy. Studies on chronic NSAID users actually show greater joint destruction, compared to patients who don’t take these medications.
· Gastric Mucosal Lesions and NSAIDs
Remember that every patient heals differently, and recovery depends on overall health status and how frequently a patient uses an affected area. Regardless of health status, prolotherapy may be the answer to effectively reduce or eliminate chronic pain.
References
1. Reeves, K.D., & Hassanein, K. (2000). Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Alternative Therapies of Health Medicine, 6(2), 68-74, 77-80.
2. Liu, Y., et al. (1983). An in-situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Connective Tissue Research, 11, 95-102.
3. Hackett, G.S., & Henderson, D.G. (1955). Joint stabilization: An experimental, histologic study with comments on the clinical application in ligament proliferation. American Journal of Surgery, 89, 968-973.
Marc Darrow is board-certified in physical medicine and rehabilitation and is the medical director of the Darrow Wellness Center in West Los Angeles. He’s also an assistant clinical professor of medicine at UCLA and author of Prolotherapy, The Collagen Revolution: Living Pain Free. He can be reached at (310) 231-7000.
Injection Ingredients
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
Part two of article segment Injecting Relief Prolotherapy Can Effectively Reduce Chronic Pain
Injection Ingredients
Injection ingredients for Prolotherapy consist of compounds that alleviate chronic pain. To trigger the healing process, clinicians use mild chemical irritants, such as phenol, guaiacol or tannic acid.
After injection, these substances attach to cell walls to stimulate the body’s reactive healing process. Some clinicians prefer to use chemotactic agents, such as sodium morrhuate, a fatty acid derived from cod liver oil.
Osmotic shock agents—the most frequently used compounds in Prolotherapy—are simple compounds, such as dextrose and glycerine. They work by causing cells to lose water, which leads to cellular dehydration and then inflammation, triggering the healing response. Because these ingredients are water-soluble, they’re excreted from the body after producing the desired effect.
Practitioners can add cofactors, such as the anti-oxidant mineral manganese. Or they can use a combination of glucosamine sulfate and condroitin sulfate, which may aid arthritic joint repair. Based on the combinations of compounds, these cofactors may increase efficacy.
Research by Liu observed that efficacy. In a study of prolotherapy’s effectiveness, Liu injected a 5 percent sodium morrhuate solution into the medial collateral ligaments of rabbits. After five injections, the ligament mass increased 44 percent, thickness increased 27 percent, and strength of the ligament bone junction increased 28 percent.2
Liu’s research confirmed the results of an earlier study; Dr. Hackett and colleagues examined the proliferant Sylnasol when it was injected into rabbit tendons.3 After 48 hours, an early inflammatory reaction surrounding the nerves and blood vessels with lymphocytic (immune system cells that remove damaged tissue) infiltration occurred in the area between two tendons and the tendons and sheath.
Two weeks after injections, fibrous tissue existed. Lymphocytic infiltration had diminished, although small levels were present, which indicated that new white fibrous tissue was still being stimulated. One month after injection, fibrous tissue was present, and lymphocytic and fibroblastic (immune system rebuilding cells) activity had diminished. In other words, the rebuilding cells had finished their job and moved on.
Although Prolotherapy compounds work differently and motivate the body to heal through various natural responses, the end result is the same: It cures pain by building new tissue and stabilizing joints.
Before administering prolotherapy, you should examine a patient by carefully and gently pressing on an area suspected of causing pain. You’ll know where to apply the prolotherapy injection when your touch elicits an intense pain reaction—a trigger or tender point.
Most of the prolotherapy solutions have a “double-edged” effect and should produce anesthetic and proliferant qualities. For example, the anesthetic agent alleviates the “pain trigger” and lets you know a solution was placed in the proper area. Simultaneously, the proliferant agent begins strengthening ligaments and tendons at the trigger point or tender point site with the Prolotherapy Injections.
Injections at trigger points cause irritation that stimulates the body’s natural process for repairing damaged tissue. It does so by causing an influx of fibroblasts and chrondroblasts, the healing cells that create collagen and cartilage. Joints are gradually pulled back into proper alignment as newly produced collagen reinforces muscles, tendons and ligaments. Then, as collagen shrinks, it tightens the joint capsule and prevents excessive, unnatural movement.
Injecting Relief Prolotherapy Can Effectively Reduce Chronic Pain
March 17, 2011 by Dr. Marc Darrow, M.D.
Filed under Prolotherapy Medical Literature
ADVANCE MAGAZINE
By Marc Darrow, MD, JD, QME
The idea of introducing an irritant to an injured joint certainly isn’t new. In ancient Greece, Hippocrates used heated metal probes to treat dislocated and painful shoulders of javelin throwers. He believed this technique created tough scar tissue that tightened the shoulder capsule and kept the joint in place.
George S. Hackett, MD, continued to build on Hippocrates’ theories in 1939. While working with car accident survivors, he realized that patients experienced pain when ligaments and tendons were injured. He believed that repairing connective tissue could resolve most of the pain. Dr. Hackett introduced an irritating compound to activate the body’s natural mechanisms and prompt production of new collagen tissues—a proliferation process that became known as Prolotherapy.
Also known as proliferation therapy, Prolotherapy is a pain management technique that can treat degenerative or chronic injury to ligaments, tendons, muscle fascia and joint capsular tissue. It also can be effective for areas that are painful, but not tender to the touch, such as the inside of a joint.
Through injections, Prolotherapy allows rapid production of collagen and cartilage.1 Collagen, a naturally occurring protein in the body, is a crucial element to the formation of new connective tissue. And healthy connective tissue creates a solid foundation to hold the skeletal infrastructure together.
Healing Mechanisms
Prolotherapy helps produce collagen by injecting mild chemical or natural irritants, such as dextrose—sugar. The injections stimulate the immune system’s healing mechanism to create collagen naturally. This strengthens and restores joints, which provides permanent pain relief.
Consider a condition such as chronic pain, in which injured, loose or stretched out ligaments often cause ligament laxity. Laxity produces pain and discomfort, especially during movements. This occurs because the connection of ligaments and tendons to bone may be inflamed, and a joint may be moving beyond its normal range of motion.
The body, therefore, must create collagen to heal injured tendons and ligaments. But it doesn’t provide ligaments and tendons with a proper blood supply, which means lower collagen production and a poor chance for complete healing.
The same holds true in cases of degenerative disease and aging. In particular, collagen may dry out and lose its stretching ability. This process is more severe in some people, and researchers don’t know why. Theories behind this deficiency include poor genetic makeup, blood type with specific dietary requirements, viral or bacterial load, pathological conditions, body acidity or food allergies.
In healthy ligaments or tendons, collagen fibers are flexible and elastic. But injuries can stretch fibers beyond their designed lengths, and repetitive motion frays or tears them. When tissues are stretched beyond their normal limits, inflammation occurs. A patient experiences inflammation, the immune system’s response to injury, when the body tries to heal damage. However, a weakened immune system or severe injury also can restrict the ability of ligaments and tendons to heal correctly. Since connective tissue around joints and cartilage has such poor blood circulation, injuries to connective tissue are often irreparable. In a future article we will go into great detail concerning Prolotherapy Injections and PRP treatment.
The key to prolotherapy is stimulating collagen development and growing new ligament and tendon tissue. By growing stronger ligaments and tendons, you can repair the injury, and reverse the degenerative cycle of arthritis and wear-and-tear disorders.
