Answers to some of your questions regarding Proliferative therapy

1. I HAVE NOT HEARD OF PROLIFERATIVE THERAPY BEFORE. WHY? Answer: Proliferative therapy is not taught in most medical schools. Unless a doctor has taken the extra training required to be an effective proliferative therapy doctor they may not be aware of the beneficial effects of proliferative therapy. At times, one proliferative therapy procedure may take up to an hour and many clinics cannot afford to take this amount of time for one patient. They base their practice in volume and have to run as many patients as possible in and out of the office in any single day. At times you are treated by a physician extender and don’t even see the doctor at all. Also, many doctors and patients want a “quick fix” as provided with medications. Lastly, most insurance companies consider it “investigational” and “alternative”, and it is not covered by your policy.

2. WHAT SIDE EFFECTS CAN I EXPECT? Answer: Side effects of proliferative therapy injections are usually minimal and may include temporary soreness, stiffness and occasional bruising in the injection site. To relief the discomfort non-anti-inflammatory over the counter pain medication such as Tylenol may be taken as needed. Do not take Advil, Aleve, BC powder, Mobic, Celebrex and the like since these interfere with Proliferative therapy.

3. DOES PROLOTHERAPY HURT? Answer: The amount of discomfort varies. It depend upon each patient and their individual condition, Normally females are more tolerant to proliferative therapy injections than men.

4. CAN PROLIFERATIVE THERAPY CURE ALL ISSUES? Answer: Of course not. No single treatment modality is capable of treating all conditions and proliferative therpy is no exception. Additionally it is not an overnight cure.

5. IS PROLOTHERAPY THE SAME AS CORTISONE INJECTIONS? Answer: No it is not. Cortisone is a steroid and stops the inflammatory process and prevents tissue healing. Cortisone is not part of the proliferative therapy injection.

6. WHAT SOLUTIONS ARE USED? Answer: A typical proliferant solution consists of Lidocaine (an anesthetic), 50% dextrose (a sugar solution), and methycobalamine (B12). Sodium morrhuate may be added to increase the proliferative  effects but this last ingredient increases the risks and we hardly use it.

7. IS PROLIFERATIVE THERAPY SAFE? Answer: Yes, is very, very safe when performed by an MD or DO trained in proliferative therapy. Procedures are always carried out using sterile techniques and either fluoroscopic or ultrasound guidance. Each patient’s condition is unique and individualized.

8. HOW MANY TREATMENTS ARE NEEDED? Answer: The number of treatments varies and will depend upon the severity of the problem and their unique condition. The average person usually receives 4-6 treatments, with some needing more and some needing less. Treatments are normally given every 3 to 4 weeks apart on a decreasing basis. Maintenance treatments may be needed from time to time. 


References about Proliferative therapy


There will be those out there that will tell you that there are no references about proliferative therapy or that it is experimental or that it does not work. Those statements are due to the fact that they have no clue or experience with proliferative therapy because they have no training in it. Just pure ignorance.  Here are just a few of the references available. 




1. Banks A: A rationale for prolotherapy. J Orthop Med (UK)

13:54–59, 1991.

2. Berl T, Siriwardana G, Ao L, et al: Multiple mitogen-activated

protein kinases are regulated by hyperosmolality inmouse IMCD cells. Am J Physiol 272:305–311, 1997.

3. 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.

4. 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.

5. Bonica J: Anatomic and physiologic basis of nociception and

pain. In Bonica JJ (ed): The Management of Pain, 2nd ed.

Philadelphia, Lea & Febiger, 1990, pp 28–94.

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

7. Bujia J, Pitzke P, Kastenbauer E, et al: Effect of growth factors on matrix synthesis by human nasal chondrocytes cultured in monolayer and in agar. Eur Arch Otorhinolaryngol (Germany) 253:336–340, 1996.

8. Caruccio L, Bae S, Liu A, et al: The heat-shock transcription factor HSF1 is rapidly activated by either hyper- or hypoosmotic stress in mammalian cells. Biochem J 327:341–347,1997.

9. 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.

10. 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.

11. Dorman T, Ravin T: Diagnosis and Injection Techniques in Orthopedic Medicine. Baltimore, Williams & Wilkins, 1991.

12. Dunham B, Koch R: Basic fibroblast growth factor and insulin like growth factor I support the growth of human septal chondrocytes in a serum-free environment. Arch Otolaryngol Head Neck Surg 124:325–330, 1998.

13. Fladeby C, Bjonness B, Serck-Hanssen G: GLUT1-mediated glucose transport and its regulation by IGF-I in cultured bovine chromaffin cells. J Cell Physiol 169:242–247, 1996.

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

15. Gayral L, Neuwirth E: Oto-neuro-ophthalmologic manifestations of cervical origin: Posterior cervical sympathetic syndrome of Barré-Lieou. N Y State J Med 54:1920–1926, 1954.

16. Grieve E: Mechanical dysfunction of the sacroiliac joint. Int Rehabil Med 5:46–52, 1983.

17. Hackett G: Joint stabilization through induced ligament sclerosis. Ohio St Med J 49:877–884, 1953.

18. Hackett G: Shearing injury to the sacroiliac joint. J Int Coll

Surg 22:631–642, 1954.

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

20. Hackett G: Prolotherapy in whiplash and low back pain.

Postgrad Med 27:214–219, 1960.

21. Hackett G: Prolotherapy for sciatica from weak pelvic ligaments and bone dystrophy. Clin Med 8:2301–2316, 1961.

22. Hackett G, Huang T, Raftery A: Prolotherapy for headache.

Headache 2:20–28, 1962.

23. Hackett G, Hemwall G, Montgomery G: Ligament and Tendon Relaxation Treated by Prolotherapy, 5th ed. Oak Park, IL, Gustav A. Hemwall, 1992.

24. Hemwall G: Barre-Lieou syndrome. J Orthop Med11:79–81, 1989.

25. Horner A, Kemp P, Summers C, et al: Expression and distribution of transforming growth factor-beta isoforms and their signaling receptors in growing human bone. Bone 23:95–102, 1998.

26. Hunt W, Baird W: Complications following injections of

sclerosing agent to precipitate fibro-osseous proliferation. J

Neurosurg 18:461–465, 1961.

27. Johnson LL: Arthroscopic abrasion arthroplasty. In Mcginty

JB (ed): Operative Arthroscopy. New York, Raven Press,

1991, pp 341–360.

28. Kang H, Kang ES: Ideal concentration of growth factors in

rabbit’s flexor tendon culture. Yonsei Med J 40:26–29, 1999.

29. Kayfetz D, Blumenthal L, Hackett G, et al: Whiplash injury and other ligamentous headache—Its management with prolotherapy.Headache 3:1–8, 1963.

30. Keplinger J, Bucy P: Paraplegia from treatment with sclerosing

agents. JAMA 173:113–115, 1960.

31. Klein R, Bjorn C, DeLong B, et al: A randomized doubleblind

trial of dextrose-glycerine-phenol injections for chronic low back pain. J Spinal Disord 6:23–33, 1993.

32. Krump E, Nikitas K, Grinstein S: Induction of tyrosine phosphorylation and Na+/H+ exchanger activation during shrinkage of human neutrophils. J Biol Chem 272:17303– 17311, 1997.

33. Leadbetter W: Soft tissue athletic injuries. In Fu FH (ed): Sports Injuries: Mechanisms, Prevention, Treatment. Baltimore, Williams & Wilkins, 1994, pp 736–737.

34. 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.

35. 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.

36. 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.

37. Mitchell N, Shephard N: The resurfacing of adult rabbit articular

cartilage by multiple perforations through the subchondral bone. J Bone Joint Surg 58A:230–233, 1976.

38. Myers A: Prolotherapy treatment of low back pain and sciatica.

Bull Hosp Joint Dis 22:48–55, 1961.

39. Naeim F, Froetscher L, Hirschberg GG: Treatment of the chronic iliolumbar syndrome by infiltration of the iliolumbar ligament. West J Med 136:372–374, 1982.

40. Nakamura N, Shino K, Natsuume T, et al: Early biological effect of in vivo gene transfer of platelet-derived growth factor (PDGF)-B into healing patellar ligament. Gene Ther 5:1165–1170, 1998.

41. 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.

42. 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.

43. Ongley M, Klein R, Dorman T, et al: A new approach to the treatment of chronic low back pain. Lancet 2:143–146, 1987.

44. Ongley M, Dorman T, Eck B, et al: Ligament instability of knees: A new approach to treatment. Manual Med 3:152–154, 1988.

45. Otsuka Y, Mizuta H, Takagi K, et al: Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full-thickness defects of articular cartilage. Dev Growth Differ 39:143–156,1997.

46. Pelletier J, Caron J, Evans C, et al: In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 40:1012–1019, 1997.

47. Pugliese G, Pricci F, Locuratolo N, et al: Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions: Relation to glucose-enhanced extracellular matrix production. Diabetologia 39:775–784, 1996.

48. Reeves KD: Mixed somatic peripheral nerve block for painful or intractable spasticity: A review of 30 years of use. Am J Pain Mgmt 2:205–210, 1992.

49. Reeves KD: Treatment of consecutive severe fibromyalgia patients with prolotherapy. J Orthop Med 16:84–89, 1994.

50. Reeves KD: Prolotherapy: Present and future applications in soft tissue pain and disability. Phys Med Rehabil Clin North Am 6:917–926, 1995.

50a. 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].

50b. 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].

51. Roos MD, Han IO, Paterson AJ, et al: Role of glucosamine synthesis in the stimulation of TGF-alpha gene transcription by glucose and EGF. Am J Physiol 270:803–811, 1996.

52. Ruis H, Schuller C: Stress signaling in yeast. Bioessays

17:959–965, 1995.

53. Sadoshima J, Izumo S: Cell swelling rapidly activates Src tyrosine kinase, a potential transducer of mechanical stress in cardiac myocytes [abstract]. Circulation 1(Suppl 1):409, 1996.

54. Schneider RC, Liss L: Fatality after injection of sclerosing agent to precipitate fibro-osseous proliferation. JAMA 170:1768–1772, 1959.

55. Schultz LW: Twenty years experience in treating hypermobility of the temporomandibular joints. Am J Surg 92:925–928, 1956.

56. Shida J, Jingusih S, Izumi T, et al: Basic fibroblast growth factor stimulates articular cartilage enlargement in young rats in vivo. J Orthop Res 14:265–272, 1996.

57. Spindler KP, Imro AK, Mayes CE: Patellar tendon and anterior

cruciate ligament have different mitogenic responses to platelet-derived growth factor and transforming growth factor beta. J Orthop Res 14:542–546, 1996.

58. Szaszi K, Buday L, Kapus A: Shrinkage-induced protein tyrosine phosphorylation in Chinese hamster ovary cells. J Biol Chem 272:16670–16678, 1997.

59. van Beuningen H, Glansbeek H, van der Kraan P, et al: Differential effects of local application of BMP-2 or TGFbeta1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage 6:306–317,1998.

60. Ward CW, Gough KH, Rashke M: Growth factors in surgery. Plast Reconstr Surg 97:469–476, 1996.

61. Wakitani S, Imoto K, Kimura T, et al: Hepatocyte growth factor facilitates cartilage repair much better than saline control.Full thickness articular cartilage defect studied in rabbitknees. Acta Orthop Scand 68:474–480, 1997.

62. Zubay G: Integration of metabolism in vertebrates. In Zubay G (ed): Biochemistry, 4th ed. Dubuque, IA, Wm. C. Brown,1998, p 691.