Prolotherapy – An Introduction for Health Care Professionals

Dr. Friz J. Berghamer BSc ND

Prolotherapy, also known as Regenerative Injection Therapy or Growth Factor Stimulation Injection Therapy, is an injection technique that uses various inflammatory solutions to promote tissue repair or growth.  Although inducing inflammation in a damaged tissue may seem counterproductive, when the physiology of tissue repair is properly understood, prolotherapy makes a lot of sense.  And when the last options left to a patient are life with chronic pain and/or surgery, prolotherapy can be an effective and inexpensive solution. 

Prolotherapy is of benefit when the severity or repetition of soft tissue injuries is such that the normal healing of sprains or strains is insufficient.  Sprains and strains often result in chronic pain when the healing response is unable to return the tissues to optimal length and/or tensile strength (this type of injury is known as connective tissue insufficiency (CTI)).[1] When connective tissue is functionally insufficient, load bearing in CTI stimulates local pain mechanoreceptors that are a source of chronic pain.[2]  CTI is directly related to myofascial pain because activation of these same mechanoreceptors cause sustained twitch contractions which create trigger points and taut bands of muscle.2  When patients present with chronic muscle pain and trigger points, it is advisable to look at the associated connective tissues to determine if CTI is a cause.  If so, prolotherapy can be used to initiate healing in the connective tissues.  During a normal healing response, cell damage triggers an inflammatory healing cascade of cells and growth factors within 48 hours which is followed by procollagen deposition within one week and maturation to collagen by 8 weeks.[3]  In order for maturation to occur, the tissue is dehydrated in order to cause constriction, tightening and thickening of weak or loose ligaments, tendons and joint capsules.  Growth factors released in response to injury are only elevated for a short time which means that full healing is dependent upon the maturation phase.3   If significant or repetitive damage has compromised the connective tissue, and the initial burst of growth factors can be insufficient for full healing and the tensile deficits may not be optimally corrected.  In these instances, prolotherapy can be used to stimulate the release of growth factors which will resume the healing process. 

Pathologic lesions of soft-tissue that result in chronic pain are degenerative rather than inflammatory in nature.[4]  Degenerative tissues have low levels of growth factors.  Similar degenerative changes have also been noted in osteoarthritis at the periosteal junction where both ligaments and tendons attach to bone.  Thus, tissues that have been chronically sprained or strained are not unlike tissues that are osteoarthritic.  In both instances the re-introduction of growth factors to these areas can initiate new cell growth and collagen deposition in both connective tissue (fibroblasts) and cartilage (chondrocytes).[5] [6] [7]   The injection of inflammatory substances at the periosteal junction stimulates the inflammatory cascade to recreate an injury without stretching or deforming the tissue.[8] This results in the recruitment of cells that will release the necessary growth factors required for a healing response. In animal studies, researchers noted an increased presence of growth factors at injection sites after prolotherapy.8,9  Analysis of the injected tissue revealed an increase in ligament thickness, enlargement of the tendinoosseous junction and an increase in the tensile strength of tendons and ligaments.[9],[10] There is a large body of anecdotal and clinical evidence to support prolotherapy and the number of studies in humans is on the rise. Research is revealing the benefits of prolotherapy in improving joint structure, function and range of motion while helping to decrease or resolve chronic pain.  A recent prospective, randomized, double-blind study by K. Dean Reeves, M.D., showed how intra-articular injections of dextrose could tighten human ACL ligaments.[11] Reeves et al. also completed two studies on osteoarthritis of the knees and fingers that indicated statistically significant clinical benefit from dextrose injections.[12]

Several proliferants can be used in prolotherapy as the inflammatory agent: dextrose, phenol, sarapin, sodium morrhuate and/or glycerin; however, dextrose is the predominantly used agent.  Simple dextrose injected into damaged or degenerative tissues causes cell proliferation and the release of a number of growth factors.[13] [14] [15] Proliferants are mixed with a local anaesthetic such as procaine or xylocaine.  The simplest prolotherapy solution is 12.5% Dextrose with 0.5% Lidocaine. The dextrose makes the solution more concentrated than blood, acting as a strong proliferant. Lidocaine is an anesthetic that helps reinforce the diagnosis because the patient will experience immediate pain relief after the prolotherapy injections. Although the use of dextrose requires more precise needling than other proliferants, cellular disruption is minimized and nerve damage has not been reported. 

The obvious prolotherapy patient is one who has had a chronic injury or who has degenerative joint changes.  However, many patients who have chronic pain do not show clinical ligament laxity on examination.  These patients may have chronic pain, joints that pop or click, have taut bands of muscles and trigger points, increased stiffness, decreased range of motion, a feeling of muscular weakness or heaviness, feel a need to self-manipulate or have manipulations done that are of only brief benefit, and have pseudoradicular pain, extremity numbness, hyperalgesia or a burning sensation. In such cases, prolotherapy is an early choice to help resolve pain. With new strains or sprains, it is recommended that prolotherapy be considered after the normal healing time has been allowed (6-8 weeks) and when pain has lasted for more than two months.  One might consider intervening with prolotherapy earlier than 8 weeks depending on chronicity and/or severity.  With prolotherapy, if improvement is not noted within several treatments, the diagnosis should be reconsidered. Most patients will notice benefit within two to three sessions, and most areas require weekly injections for 6 – 8 weeks. 

Prolotherapy injections themselves are painful which is why local anaesthetics are employed.  Nerve blocks can be used if needed. Patients will experience soreness and bruising at the site of injection that usually lasts for 48-72 hours post injection. 

 Who may potentially benefit from prolotherapy?

•   Have had pain for greater than 6 weeks
•   Have to change position every 15 min or less
•   Only get temporary relief from Manipulations (adjustments)
•   Have joints that click, pop, snap, or grind
•   Have arthritis or degenerative joint disease
•   Have nagging sports injuries
•   Have had orthopedic surgery and still have pain
•   Have pain from a ligament or tendon injury
•   Have pain from degenerative arthritis with good ROM
•   Is healthy other than the pain
•   When activities increase the pain
•   Pain associated with muscle spasms
•   Pain is better with rest
•   When MRI/CAT/x-rays do not show anything
•   Normal sensation in the joint

What conditions may benefit from prolotherapy treatments?

• Arthritis                                               
• Fibromyalgia                     
• Herniated discs                
• Low back pain                                   
• Spondylolisthesis            
• Sciatica                                                                 
• Neck pain                                           
• Whiplash                            
• Reflex sympathetic dystrophy
• Tension headaches                        
• Coccydynia                        
• Repetitive strain injuries
• Carpal tunnel syndrome                              
• Migraines                           
• Myofascial pain syndromes
• Sprains to any joint                        
• TMJ dysfunction              
• Heel spurs
• Plantar fasciitis                                 
• Rotator Cuff strains        
• Osgood Schlatter Syndrome
• A-C joint sprains                              
• Tendonitis                          
• ACL/PCL/MCL/LCL sprains
• Tennis elbow                                    
• Golfer’s elbow

[1] Frank C, Amiel D, Woo SL-Y, et al: Normal ligament properties and ligament healing. Clin Orthop Res 196:15–25, 1985.

[2] Biedert R, Stauffer E, Freiderich N: Occurrence of free nerve endings in the soft tissue of the knee joint. Am J Sports Med 20:430–433, 1993.

[3] Buckwalter J, Cruess R: Healing of musculoskeletal tissues. In Rockwood CA, Green DP (eds): Fractures. Philadelphia, J.B. Lippincott, 1991.

[4] Best T: Basic science of soft tissue. In DeLee JC, Drez D Jr (eds): Orthopaedic Sports Medicine Principles and Practice, Vol 1. Philadelphia, W.B. Saunders, 1994, p 3.

[5] Des Rosiers E, Yahia L, Rivard C: Proliferative and matrix synthesis response of canine anterior cruciate ligament fibroblasts submitted to combined growth factors. J Orthop Res 14:200–208, 1996.

[6] Lee J, Harwood F, Akeson W, et al: Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments. Iowa Orthop J 18:19–25, 1998.

[7] Marui T, Niyibizi C, Georgescu HI, et al: Effect of growth factors on matrix synthesis by ligament fibroblasts. J Orthop Res 15:18–23, 1997.

[8] Banks A: A rationale for prolotherapy. J Orthop Med (UK)13:54–59, 1991.

[9] Hackett GS: Ligament and Tendon Relaxation Treated by Prolotherapy, 3rd ed. Springfield, IL, Charles C Thomas, 1956.

[10] Liu Y, Tipton C, Matthes R, et al: An in-situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Connect Tissue Res 11:95–102, 1983.

[11] Reeves KD, Hassanein K: Randomized, 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 [in press].

[12] Reeves KD, Hassanein K: Randomized, prospective, double-blind, placebo-controlled study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: Evidence of clinical efficacy. J Altern Complement Med [in press].

[13] Di Paolo S, Gesualdo L, Ranieri E, et al: High glucose concentration induces the overexpression of transforming growth factor-beta through the activation of a platelet-derived growth factor loop in human mesangial cells. Am J Pathol 149:2095–2106,1996.

[14] Ohgi S, Johnson P: Glucose modulates growth of gingival fibroblasts and periodontal ligament cells: Correlation with expression of basic fibroblast growth factor. J Periodontal Res 31:579–588, 1996.

[15] Okuda Y, Adrogue H, Nakajima T, et al: Increased production of PDGF by angiotensin and high glucose in human vascular endothelium. Life Sci 59:455–461, 1996.