Regenerative
Injection Therapy (RIT):
Click here For a list of
Regenerative Injection Therapists/Prolotherapists who are FAPM members
Effectiveness
and Appropriate Usage
by the Florida Academy of Pain Medicine
Published in The Pain Clinic Magazine, Vol 4 # 3, June,
2002, pages 38 - 45
Position Paper Committee Members
Felix S. Linetsky, M.D.
Kenneth Botwin, M.D.
Lawrence Gorfine, M.D.
Gary W. Jay, M.D.
Raphael Miguel, M.D.
Asya Mikulinksy, M.D.
Winston Parris, M.D.
Sanford Pollak, D.O.
Albert Ray, M.D.
Lloyd Saberski, M.D.
Peter Taraschi, D.O.
Francisco Torres, M.D.
Andrea Trescot, M.D.
POSITION PAPER FROM THE FLORIDA ACADEMY
OF PAIN MEDICINE (FAPM)
ON REGENERATIVE INJECTION THERAPY (RIT)
DEFINITION OF RIT
Regenerative Injection Therapy (RIT) is
an interventional technique for treatment of chronic pain due to connective
tissue diathesis by induction of collagen chemomodulation though inflammatory,
proliferative and regenerative/reparative responses mediated by multiple growth
factors. (18, 25, 49, 50, 92, 93, 113, 114)
INTRODUCTION
The purpose of this positional paper
is:
1. To inform/familiarize the members of FAPM and the medical community at large
regarding the validity of an under-utilized, type-specific treatment for chronic
musculoskeletal pain related to connective tissue pathology.
2. To outline common indications and conditions treated with RIT, as well as
contraindications thereto.
3. To encourage the use of RIT in the treatment of appropriate painful pathology
of the connective tissue.
METHODOLOGY
To determine the validity of RIT/prolotherapy,
a position paper committee of interventional pain physicians was formed and
undertook a comprehensive review of pertinent literature. The committee reviewed
78 specific articles and nine text books, as well as 51 relevant articles and
chapters from other text books.
FINDINGS
From 1937 through 2000, more than forty
authors reported case studies, retrospective, prospective and animal experiment
studies that evaluated the results of treatment with RIT. The calculated number
of patients reported in those studies exceeded 530,000. Improvement in terms of
return to work and previous functional/occupational activities was reported in
48% to 82% of the patients. The resolution of pain symptomatology was evaluated
differently in various studies and ranged from zero to 100%. Complications
included 28 pneumothoraces, two requiring chest tubes, 24 allergic reactions,
one grand mal seizure, and one aseptic meningitis.
The findings of the FAPM committee substantially contrast with the position of
the Department of Health and Human Services (DHHS), Florida Workmen's
Compensation, and Medicare guidelines. The committee recommends consideration of
the use of RIT as a type-specific treatment for post-traumatic degenerative,
overuse and painful conditions of the musculoskeletal system related to
pathology of the connective tissue.
For decades, a small group of allopathic and osteopathic physicians has been
practicing the methodology known as Regenerative Injection Therapy (RIT), also
known as known in the past as prolotherapy. Pilot, retrospective, open face
prospective, and double blind placebo controlled studies have clearly indicated
RIT's effectiveness in the
treatment of chronic musculoskeletal pain arising from post-traumatic and
degenerative changes in connective tissue such as ligaments, tendons, fascia,
and intervertebral discs. (4, 5, 8-10, 12, 14-17, 20-22, 26-28, 35-36, 38-69,
73-83, 88-99, 101-104, 106-111, 113-118, 120-122, 124-128, 133-135)
Clinical and experimental electron microscopic studies have proven that
structurally the newly formed connective tissue had biomechanical properties
similar to those of normal ligaments and tendons. (78, 94, 99, 110)
Preliminary results of clinical prospective trials for chemonucleo-annuloplasty
with proliferation-causing substances show significant promise. (35, 36, 81, 97)
The literature dealing with RIT has been evaluated. This information, in
association with extensive clinical experience has found RIT to be an effective
therapy for a number of chronic pain conditions. This position paper reviews the
clinical and pathophysiological aspects of RIT. The Florida Academy of Pain
Medicine endorses RIT when utilized appropriately for the treatment of specific
chronic pain entities.
I. RIT MECHANISM OF ACTION
The RIT mechanism of action is complex
and multifaceted. Six identified components include:
1) The mechanical transection of cells and matrix induced by the needle, causes
cellular damage, stimulating an inflammatory cascade. (8, 18-20, 93, 113, 114,
118, 119, 132)
2) Compression of cells by the extracellular volume of the injected solution
stimulates intracellular growth factors. (84-86, 93, 113)
3) Chemomodulation of collagen through inflammatory proliferative,
regenerative/reparative responses induced by the chemical properties of the
proliferants and mediated by cytokines and multiple growth factors. (7, 18, 24,
45, 49-53, 84-86, 93, 113)
4) Chemoneuromodulation of peripheral nociceptors and antidromic, orthodromic,
sympathetic and axon reflex transmissions. (49, 57-64)
5) Modulation of local hemodynamics with changes in intraosseous pressure
leading to the reduction of pain. Empirical observations suggest that a
dextrose/lidocaine combination has a much more prolonged action than lidocaine
alone. (57-64, 123, 129, 138)
6) A temporary repetitive stabilization of the painful hypermobile joints,
induced by the inflammatory response to the proliferants, provides a better
environment for regeneration and repair of affected ligaments and tendons. (38,
39, 49-55, 120, 121, 124, 127)
II. PUTATIVE PAIN GENERATING STRUCTURES
ADDRESSED BY RIT
(1-45, 47-69, 71, 73-86, 89-93, 98-104, 106-111, 113-122, 124-128)
1) Ligaments: Intra-articular, periarticular, capsular
2) Tendons
3) Fascia
4) Enthesis: the zone of insertion of ligament, tendon or articular capsule to
bone
5) Intervertebral discs. Note: outer layers of the annulus represent a typical
enthesis.
III. TISSUE PATHOLOGY APPROPRIATELY TREATED WITH RIT
1) Sprain: Ligamentous injury at the
fibro-osseous junction or intersubstance disruption secondary to sudden or
severe twisting of a joint with stretching or tearing of ligaments. (24, 71, 86,
100)
2) Strain: Muscle/tendon injury at the fibromuscular or fibro-osseous interface.
When concerned with peripheral muscles and tendons, sprains and strains are
identified as separate injuries and in three stage gradations: first, second and
third degree sprain and similarly for strain. No consensus exists among authors,
and the definitions are quite vague, regarding vertebral and paravertebral
ligaments and tendons. (24, 71, 86, 100)
3) Enthesopathy: A painful degenerative pathological process that results in
deposition of poorly organized tissue, degeneration and tendinosis at the
fibro-osseous interface and transition towards loss of function. (18, 24, 71,
86, 93, 101)
4) Tendinosis/Ligamentosis: A focal area of degenerative changes due to failure
of cell matrix adaptation to excessive load and tissue hypoxia with a strong
tendency toward chronic pain and dysfunction. (71, 80, 84-86, 93, 112, 114, 119)
5) Pathologic Ligament Laxity: a post-traumatic or congenital condition leading
to
painful hypermobility of the axial and peripheral joints. (7, 8, 38-43, 47-54)
IV. INDICATIONS FOR RIT
(1-45, 47-69, 71, 73-86, 89-93, 98-104, 106-111, 113-122, 124-128))
1. Chronic pain from ligaments or tendons secondary to sprains or strains.
2. Pain from overuse or occupational conditions known as "Repetitive Motion
Disorders," i.e., neck and wrist pain in typists and computer operators,
"tennis" and "golfers" elbows and chronic supraspinatus
tendinosis.
3. Chronic postural pain of the cervical, thoracic, lumbar and lumbosacral
regions.
4. Painful recurrent somatic dysfunctions secondary to ligament laxity that
improves temporarily with manipulation. Painful hypermobility and subluxation at
given peripheral or spinal articulation(s) or mobile segment(s) accompanied by a
restricted range of motion at reciprocal segment(s).
5. Thoracic and lumbar vertebral compression fractures with a wedge deformity
that exert additional stress on the posterior ligamento-tendinous complex.
6. Recurrent painful subluxations of ribs at the costotransverse, costovertebral
and/or costosternal articulations.
7. Osteoarthritis of axial and peripheral joints, spondylosis, spondylolysis and
spondylolisthesis
8. Painful cervical, thoracic, lumbar, lumbosacral and sacroiliac instability
secondary to ligament laxity.
9. Intolerance to NSAIDs, steroids or opiates. RIT may be the treatment of
choice if the patient fails to improve after physical therapy, chiropractic or
osteopathic manipulations, steroid injections or radiofrequency denervation, or
surgical interventions in the aforementioned conditions, or if such modalities
are contraindicated.
V. SYNDROMES AND DIAGNOSTIC ENTITIES,
CAUSED BY LIGAMENT AND TENDON PATHOLOGY,
THAT HAVE BEEN SUCCESSFULLY TREATED WITH RIT
(4, 5, 8-22, 26-32, 34-70, 74-85, 87-103, 105-115, 119-121, 123-127, 131-134)
1) Cervicocranial Syndrome (cervicogenic
headaches, secondary to ligament sprain and laxity, atlanto-axial and atlanto-occipital
joint sprains, mid cervical zygoapophyseal sprains)
2) Temporomandibular Pain and Muscle Dysfunction Syndrome
3) Barre-Lieou Syndrome
4) Torticollis
5) Cervical segmental dysfunctions
6) Cervicobrachial Syndrome (shoulder/neck pain)
7) Hyperextension/Hyperflexion injury Syndromes
8) Cervical, Thoracic and Lumbar Zygoapophyseal Syndromes
9) Cervical, Thoracic and Lumbar Sprain/Strain Syndrome
10) Costo-transverse joint pain
11) Costovertebral arthrosis/dysfunction
12) Slipping rib syndrome
13) Sternoclavicular arthrosis and repetitive sprain
14) Thoracic segmental dysfunction
15) Tietze's Syndrome/
costochondritis/chondrosis
16) Costosternal arthrosis
17) Xiphoidalgia syndrome
18) Acromioclavicular sprain/arthrosis
19) Shoulder hand syndrome
20) Recurrent shoulder dislocations
21) Scapulothoracic crepitus
22) Iliocostalis Friction Syndrome
23) Iliac Crest Syndrome
24) Iliolumbar syndrome
25) Internal lumbar disc disruption
26) Interspinous pseudoarthrosis
(Baastrup's Disease)
27) Lumbar instability
28) Lumbar ligament sprain
29) Spondylolysis
30) Sacroiliac joint pain
31) Sacrococcygeal joint pain
32) Gluteal tendonosis
33) Trochanteric tendonosis
34) Myofascial Pain Syndromes
35) Ehlers-Danlos Syndrome
36) Osgood-Schlatter disease
37) Ankylosing Spondylitis
(Marie-Strumpell disease)
38) Failed Back Syndrome
39) Fibromyalgia Syndrome
40) Foot and/or ankle:
· Sinus Tarsi Syndrome
· Metatarsalgia
· Chronic Ankle Sprain
· Instability
· Laxity of ligaments
VI. CONTRAINDICATIONS TO RIT
1. Allergy to anesthetic or proliferant
solutions or their ingredients such as dextrose, sodium morrhuate or phenol.
2. Acute non-reduced subluxations or dislocations.
3. Acute arthritis (septic or post-traumatic with hemarthrosis)
4. Acute bursitis or tendinitis
5. Capsular pattern shoulder and hip designating acute arthritis accompanied by
tendinitis.
6. Acute gout or rheumatoid arthritis
7. Recent onset of a progressive neurologic deficit including but not limited to
(severe intractable cephalgia, unilaterally dilated pupil, bladder dysfunction,
bowel incontinence, etc).
8. Requests for a large quantity of sedation and/or narcotics before and after
treatment.
9. Paraspinal neoplastic lesions involving the musculature and osseous
structures.
10. Severe exacerbation of pain or lack of improvement after local anesthetic
blocks.
11. Relative contraindications: central spinal canal, lateral recess and neural
foraminal stenosis.
VII. COMMONLY UTILIZED SOLUTIONS
The most common solutions are dextrose
based. Dilutions can be made with local anesthetic, for example, 1 ml of 50%
dextrose mixed with 3 ml of 1% lidocaine. A gradual progression to 25% Dextrose
solution has also been utilized. (27, 50, 93, 113, 114)
For intra-articular injection of the knee, 25% dextrose solution was utilized
for decades. (50) Recently, a 10% Dextrose solution has been investigated and
also proven to be effective. (115)
5% sodium morrhuate is a mixture of sodium salts of saturated and unsaturated
fatty acids of cod liver oil and 2% benzyl alcohol. Note that the benzyl alcohol
chemically is very similar to phenol and acts as a local anesthetic and
preservative. (8, 50, 93, 101, 124)
Dextrose phenol glycerine solution consists of 25% dextrose, 2.5% phenol and 25%
glycerine and is referred to as DPG or P2G. In all referenced studies, it was
diluted with a local anesthetic of the practitioner's choice prior to injection.
Dilution reported ratios are 1:1, 1:2 and 2:3. (5, 20-22, 26, 28, 50, 78-80,
108-110)
6% phenol in glycerine solution was utilized at donor harvest sites of the iliac
crests for neurolytic and proliferative responses. (95, 135)
Other solutions utilized include pumice suspension, tetracycline, a mixture of
chondroitin sulfate, glucosamine sulfate and dextrose. (14, 36, 37, 42-44, 50,
81)
VIII. CONCLUSIONS
(1-138)
1) RIT (known in the past as Prolotherapy) is a valuable method of treatment for
correctly diagnosed chronic painful conditions of the locomotive systems.
2) Thorough familiarity of the physician with normal, pathologic,
cross-sectional and clinical anatomy, as well as anatomical variations and
functions are necessary to utilize this technique appropriately.
3) Current literature supports manipulation under local joint anesthesia and a
series of local anesthetic blocks for diagnosis of somatic pain.
4) Use of RIT in an ambulatory setting is an acceptable standard of care in the
community.
5) Current literature suggests that NSAIDs and steroid preparations have limited
utility in chronic painful overuse conditions and in degenerative painful
conditions of ligaments and tendons. However, they are occasionally helpful to
curb a significant inflammatory reaction to proliferants. Microinterventional
regenerative techniques and proper rehabilitation up to six months or a year
supported with mild opioid analgesics may be more appropriate.
IX. SUMMARY
RIT is a safe and effective treatment
modality that is very useful in a significant number of pain syndromes arising
from ligament and tendon diathesis, as well as other clearly delineated pain
problems.
Physicians who use RIT must be knowledgeable in clinical anatomy and function
and should be properly trained in this technique via a combination of
seminars/workshops, apprenticeships or visiting fellowships in order to safely
and effectively utilize this treatment. The Florida Academy of Pain Medicine
endorses RIT when administered appropriately for the treatment of specific
chronic pain entities.
REFERENCES FOR RIT POSITION PAPER
1. Agur, A. et al Grant's atlas of
anatomy, 9th edition; Williams and Wilkins; 1991
2. April, C. et al "Cervical zygapophyseal joint pain patterns II: A
clinical evaluation"; Spine:15:6; 1990
3. Ashton, I. et al "Morphological basis for back pain: The demonstration
of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in
the ligamentum flavum; Journal of Orthopaedic Research; 10:72-78, Raven Press
LTD; New York; 1992
4. Bahme, B. Observations on the treatment of hypermobile joints by injections.
The Journal of the American Osteopathic Association; 45:3; 101-109; Nov 1945
5. Barbor, R. "A treatment for chronic low back pain"; Proceedings
from the IV International Congress of Physical Medicine; Paris; September 6-11,
1964
6. Barnsley, L et al "Lack of effect of intraarticular corticosteroids for
chronic pain in the cervical zygapophyseal joints"; New England Journal of
Medicine; 330:15; 1047-1050; April 14, 1994
7. Best, T. "Basic Science of Soft Tissue", in Delee jc, drez, d jr.,
(eds) J Orthopedic Sports Medicine Principles and Practice (Vol 1),
Philadelphia, PA, Saunders; 1994
8. Biegeleisen, H.I. Varicose veins, related diseases and sclerotherapy: A guide
for practitioners; Eden Press; 1984
9. Blaschke, J. Conservative management of intervertebral disk injuries; J. of
OK State Med Assoc; 54:9: Sept 1961
10. Blumenthal, L. "Injury to the cervical spine as a cause of
headache"; Postgraduate Medicine; Vol 56:3; September 1974
11. Bogduk, N. Clinical anatomy of the lumbar spine and sacrum, third edition;
Churchill Livingstone; 1997
12. Bourdeau, Y. Five-year follow-up on sclerotherapy/prolotherapy for low back
pain: Manual Medicine:3:155-157; 1988
13. Broadhurst, N. et al "Vertebral mid-line pain: Pain arising from the
interspinous spaces"; The Journal of Orthopaedic Medicine; 18:1:2-4; 1996
14. Chase, R. "Basic sclerotherapy"; Osteopathic Annals; December 1978
15. Coleman, A. "physician electing to treat by prolotherapy alters the
method at his peril"; J of the National Medical Assoc; 60:4: 346-348; July
1968
16. Compere, E. et al "Persistent Backache", Med. Clin. of N. Amer.,
42:299-307; Jan 1958
17. Coplans, C. "The use of sclerosant injections in ligamentous
pain", pp 165-169, in Disorders of the lumbar spine by Heflet, A., Grueble
L. and David M. 1972
18. Cotran, R.S. et al Robbins pathologic basis of disease, W.B. Saunders,
Philadelphia, PA; 1999
19. Cousins, M. et al Neural Blockage in Clinical Anesthesia and Management of
Pain, J.B. Lippincott co.; 1988
20. Cyriax, J. Textbook of orthopaedic medicine, Volume one diagnosis of soft
tissue lesion; Bailliere Tindall; London; 1982
21. Cyriax, J. Illustrated manual of orthopaedic medicine, second edition,
Butterworth Heinemann; 1993
22. Cyriax, J. Textbook of orthopaedic Medicine Volume 1, 5th edition; Williams
and Wilkins Co.; 1969
23. DesRosiers, E. et al "Proliferative and matrix synthesis response of
canine anterior cruciate ligament fibroblasts submitted to combined growth
factors"; J. of Orth Research; 14: p200-208; 1996
24. Dorland's Illustrated Medical Dictionary 26th Edition, W.B. Saunders Co.;
1985
25. Dorman, T. et al Diagnosis and injection techniques in orthopedic medicine,
Williams and Wilkins, publisher, 1991
26. Dorman, T. Storage and release of elastic energy in the pelvis: dysfunction,
diagnosis and treatment, as published in Low back pain and its relation to the
sacroiliac joint, San Diego, CA 1992
27. Dorman, T. Prolotherapy: A Survey, Journal of Orthopaedic Medicine, 15:2,
49-50, 1993
28. Dorman, T. Prolotherapy in the lumbar spine and pelvis, Hanley and Belfus,
Inc, Philadelphia, May 1995
29. Dreyfuss, P. et al "Atlanto-occipital and lateral atlanto-axial joint
pain patterns"; Spine: 19:10; 1125-1131; 1994
30. Dreyfuss, P. et al "Thoracic zygapophyseal joint pain patterns: A study
in normal volunteers"; Spine: 19:7; 807-811; 1994
31. Dreyfuss, P. "Differential diagnosis of thoracic pain and
diagnostic/therapeutic injection techniques"; ISIS newsletter, pp 10-29
December 1997
32. Dreyfuss, P. et al "Muja: Manipulation Under Joint
Anesthesia/Analgesia: A Treatment Approach for Recalcitrant Low Back Pain of
Synovial Joint Origin", Journal of Manipulative and Physiological
Therapeutics, Vol 18,#8,pp 537-546; Oct. 1995
33. Dussault, R. et al "Facet joint injection: Diagnosis and therapy";
Applied Radiology: 35-39; June 1994
34. Dwyer, A. et al "Cervical zygapophyseal joint pain patterns I: A study
in normal volunteers"; Spine: 15:6; 1990
35. Eek, B. New directions in the treatment of disc pain as in Diagnosis and
treatment of discogenic pain international spinal injection society 4th annual
meeting; Vancouver; BC; Canada; pp 47-48; August 16, 1996
36. Eek, B. Intradiscal Injection Therapy for Chronic Discogenic Pain, a
prospective trial, proceedings of the American Association of Orthopedic
Medicine Annual Meeting, Memphis, Tennessee, April 2001
37. Freemont, A. et al "Nerve ingrowth into diseased intervertebral disc in
chronic back pain"; Lancet; 350:178-181; 1997
38. Gedney, E. Special technic hypermobile joint: a preliminary report,
Osteopathic profession, p 30-31 June 1937
39. Gedney, E. The hypermobile joint-further reports on injection method, read
before Osteopathic clinical society of Pennsylvania, Feb 13 1938
40. Gedney, E. Disc syndrome, Osteo prof, Sept, pp 11-15, 38-46 1951 50.
41. Gedney, E. Use of sclerosing solution may change therapy in vertebral disk
problem, The osteopathic profession; pp. 34, 38 and 39, 1113 April 1952
42. Gedney, E. Technic for sclerotherapy in the management of hypermobile
sacroiliac; The Osteopathic Profession; 16-19 and 37-38; August 1952
43. Gedney, E. Progress report on use of sclerosing solutions in low back
syndromes. The Osteopathic Profession; 18-21, 40-44 August 1954
44. Gedney, E. "The Application of Sclerotherapy in Spondylolisthesis and
Spondylolysis", The Osteopathic Profession, pp 66-69 and 102-105, Sept.
1964
45. Gray's anatomy, 38th British edition, Churchill Livingston, Pearson
Professional Limited; 1995
46. Grayson, M. Sterile meningitis after lumbosacral ligament sclerosing
injections; The Journal of orthopaedic medicine: 16:3; 1994
47. Green, S. "Hypermobility of joints: causes, treatment and technic of
sclerotherapy", The Osteopathic Profession; pp 26-27 and pp 42-47; April
1956
48. Green, S. "The study of ligamentous tissue is regarded as key to
sclerotherapy"; The Osteopathic Prof; pp 26-29; January 1958
49. Hackett, G. Ligament and Tendon relaxation (skeletal disability)- treated by
prolotherapy, (fibro-osseous proliferation), 3rd edition, Springfield, IL,
Charles C. Thomas; 1958
50. Hackett, G. et al Ligament and tendon relaxation-treated by prolotherapy,5th
edition; 1991
51. Hackett, G. Joint stabilization through induced ligament sclerosis. Ohio
State Med. J.; 49:877-884; Oct 1953
52. Hackett, G. and Henderson, D. Joint stabilization: an experimental,
histologic study with comments on the clinical application in ligament
proliferation, American Journal of Surgery; 89;968-973 May 1955
53. Hackett, G. Joint ligament relaxation treated by fibro-osseous
proliferation, first edition, Charles C. Thomas publisher 1956
54. Hackett, G. Ligament relaxation and osteoarthritis, loose jointed vs. closed
jointed. Rheumatism, Lond;15:2:28-33, April 1959
55. Hackett, G. "Low back pain", Indust. Med. Surg., 28:416-419; Sept
1959
56. Hackett, G. "Prolotherapy in whiplash and low back pain", Postgrad.
Med. 27:214-219; 1960
57. Hackett, G. "Prolotherapy in low back pain from ligament relaxation and
bone dystrophy", Clinical Medicine 7:12, pp 2551-2561 Dec 1960
58. Hackett, G. et al "Back pain following trauma and disease prolotherapy",
military medicine; pp 517-525; July 1961
59. Hackett, G. "Prolotherapy for sciatic from weak pelvic ligament and
bone dystrophy", Clin, Med., 8:2301-2316; Dec 1961
60. Hackett, G. et al "Prolotherapy for headache: pain in the head and
neck, and neuritis", Headache, 2:20-28; April 1962.
61. Hackett, G. "Arteriosclerosis, carcinogenesis, neuritis and
osteoporosis", angiology, Vol 17:109-118, Feb 1966
62. Hackett, G. "Cause and mechanism of headache, pain and neuritis",
Headache 6:88-92, July 1966
63. Hackett, G. "Uninhibited reversible antidromic vasodilation in
pathophysiologic diseases: arteriosclerosis, carcinogenesis, neuritis and
osteoporosis", Angiology, Vol 17, #2, February 1966
64. Hackett, G. "Uninhibited reversible antidromic vasodilatation in
bronchiogenic pathophysiologic diseases", Lancet 86:398-404, Aug 1966
65. Hackett, G. "Prevention of cancer, heart, lung and other
diseases", Clin, Med. 74:19, Sept 1967
66. Haldeman, K. et al The diagnosis and treatment of sacroiliac conditions by
the injection of procaine (novocain), Journal of bone and joint surgery, vol. xx,
no. 3, July pp. 675-685; 1938
67. Hirsch, C. "An attempt to diagnose the level of a disc lesion
clinically by disc puncture"; Acta Orthop. Scand; 18:131-140; 1948
68. Hirschberg, G. et al "Treatment of the chronic iliolumbar syndrome by
infiltration of the iliolumbar ligament"; Western J. of Medicine; 136:
372-374; Apr 1982
69. Hirschberg, G. et al Diagnosis and treatment of iliocostal friction
syndromes; J of Ortho Med: 14:2: p 35-39; 1992
70. Hunt, W "Complications following injections of sclerosing agent to
precipitate fibro-osseous proliferation"; J Neurosurg; 18:461-465; 1961
71. Jozsa, L. Human tendons, anatomy, physiology and pathology, Human Kinetics,
Champaign, IL; 1997
72. Kang, H. et al "Ideal concentration of growth factors in rabbit's
flexor tendon culture": Yonsei medical journal: 40:1;pp 26-29; 1999
73. Kayfetz, D. et al "Whiplash injury and other ligamentous headache-its
management with prolotherapy"; Headache; Vol III: No I; Apr 1963
74. Kayfetz, D. "Occipito-cervical (whiplash) injuries treated by
prolotherapy", Med Trial Tech Quar, Callaghan and Co; pp.147-167 pp.09-112;
1963
75. Kellgren, J.H. "On the Distribution of Pain Arising From Deep Somatic
Structures with Charts of Segmental Pain Areas", Somatic Pain pp.35-46;
1939
76. Kidd, R. "Recent Developments in the Understanding of Osgood-Schlatter
Disease: A Literature Review," The J. of Ortho. Med., Vol. 15, No. 3,
pp.59-61, 1993
77. Kidd, R. "Treatment of Osgood-Schlatter Disease by Prolotherapy - A
Case Report," The J. of Ortho. Med., Vol 15, No 3, pp.62-63, 1993
78. Klein, R. et al "Proliferation Injections for Low Back Pain: Histologic
Changes of Injected Ligaments and Objective Measurements of Lumbar Spine
Mobility Before and After Treatment", J of Neuro and Ortho Med and Surg,
Vol 10, Issue 2, July 1989
79. Klein, R. et al "Prolotherapy: An Alternative Approach to Managing Low
Back Pain", The Journal of Musculoskeletal Medicine, pp.45-59, May 1997
80. Klein, R. Diagnosis and treatment of gluteus medius syndrome; J Orth. Med:
1373-76; 1991
81. Klein, R. Interdiscal injection Therapy for Chronic Discogenic Pain, a
prospective trial in progress, presentation at the Amer. Assn. Of Ortho. Med
workshop, Daly City, CA, Feb. 2001
82. Klein, R. et al. A randomized double-blind trial of dextrose-glycerine-phenol
injections for chronic, low back pain; J of Spinal Disorders: 6:1; p.23-33; 1993
et al
83. Koudele, C. "Treatment of joint pain"; Osteopathic Annals: 6:12;
42-45; Dec 1978
84. Leadbetter, W. Cell-matrix response in tendon injury; Clin sports med 11;
533-578; 1992
85. Leadbetter, W. Anti-inflammatory therapy and sport injury: the role of
non-steroidal drugs and corticosteroid injections; Clin sports med 14; 353-410;
1995
86. Leadbetter, W. Soft Tissue athletic Injuries: Sports Injuries: Mechanisms,
Prevention, Treatment; Williams and Wilkins, pp.736-737; 1994
87. Lee, J. et al "Growth factor expression in healing rabbit medial
collateral and anterior cruciate ligaments": Iowa Orthopaedic Journal:18
pp.19-25; 1998
88. Leedy, R. et al "Analysis of 50 low back cases 6 years after treatment
by joint ligament sclerotherapy"; Osteo Med:6; 1976
89. Leedy, R. "Applications of sclerotherapy to specific problems";
Osteopathic Medicine; pp.79-81,85,86,89-91, 94-96; Aug 1977
90. Leriche, R. Effets de l'anesthesia a la novocaine des ligaments et des
insertion tenineuses periarticulares dans certanes maladies articulares et dans
les vices de positions foncitionnells des articulations, Gaz D. Hop., 103:1294;
1930
91. Linetsky, F. et al "Regenerative Injection Therapy: History of
Application in Pain Management, Part I 1930s-1950s"; The Pain Clinic; Vol.
2:2; pp.8-13, Apr 2000
92. Linetsky, F. et al "Regenerative Injection Therapy: History of
Applications in Pain Management, Part II 1930s-1950s"; The Pain Clinic;
Vol. 3:2, pp.32-36, Apr 2001
93. Linetsky, F. et al., "Pain Management with Regenerative Injection
Therapy (RIT)", a chapter in Pain Management: A Practical Guide for
Clinicians (6th Ed.) in print
94. Liu, Y. et al "An in Situ Study of the Influence of a Sclerosing
Solution in Rabbit Medial Collateral Ligaments and its Junction Strength",
Connective Tissue Research, Vol 11, pp.95-102; 1983
95. Maher, R. "Neuron Selection in Relief of Pain. Further Experiences with
Intrathecal Injections", The Lancet; pp.16-19; Jan 1957
96. Marui, T. et al "Effect of growth factors on matrix synthesis by
ligament fibroblasts": J. or ortho research: 15:pp.18-23; 1997
97. Massie, J. et al Is it possible to stimulate fibroplasia within the
intervertebral disc?; J of Ortho Med: 15:3; p.83; 1993
98. Matthews, J. A new approach to the treatment of osteoarthritis of the knee:
Prolotherapy of the ipsilateral sacroiliac ligaments: Am J of Pain Management;
5:3; p.91-93; 1995
99. Maynard, J. et al "Morphological and Biochemical Effects of Sodium
Morrhuate on Tendons", J of Ortho Research, 3:234-248; 1985
100. Merskey, H. et al Classification of Chronic Pain, Descriptions of Chronic
Pain Syndromes and Definitions of Pain Terms (2nd Ed), IASP Press, Seattle; 1994
101. Mirman, M. Sclerotherapy, 4th Edition, Springfield, PA 19064; 1989
102. Mooney, V. Sclerotherapy in back pain? Yes if clinician is skilled; J of
Musculoskeletal medicine; p.13; Jan 1993
103. Mooney, V. Understanding, examining for, and treating sacroiliac pain; The
Journal of musculoskeletal medicine; pp.37-49; July 1993
104. Myers, A. "Prolotherapy treatment of low back pain and sciatica",
Bull Hosp Joint Disease: 22:p.48-55; 1961
105. Nakamura, N. et al "Early biological effect of in vivo gene transfer
of platelet-derived growth factor (PDGF)-B into healing patellar ligament":
Gene Therapy; 5: pp.1165-1170; 1998
106. Neff, F."A new approach in the treatment of chronic back
disabilities", The Family Physician; 9:3; Mar 1959
107. Neff, F. Low back pain and disability," Western Med.; 1:12 June 1960
108. Ombregt, L. et al A system of orthopaedic medicine, WB Saunders Co, Ltd;
1995
109. Ongley, M. et al "A New Approach to the Treatment of Chronic Low Back
Pain", The Lancet, July 18, pp.143-146; 1987
110. Ongley, M. et al Ligament instability of knees: A new approach to
treatment; Manual Medicine: 3:pp.152-154; 1988.
111. Poritt, A. The injection treatment of hydrocele, varicocele, bursae and
nevi, Proc. Royal Soc. Med., 24:81; 1931
112. Ranney, D. Chronic musculoskeletal injuries in the workplace, W.B.
Saunders, Co.; 1997
113. Reeves, K.D. Prolotherapy: Basic Science Clinical Studies and Technique as
in Lennard Pain Procedures in Clinical practice; Hanley and Belfus Inc;
Philadelphia; 2000
114. Reeves, K.D. "Prolotherapy: Present and Future Applications in Soft-
Tissue Pain and Disability", Physical Medicine and Rehabilitation Clinics
of North America, Vol 6, No. 4, pp.917-926; Nov.1995
115. Reeves, K.D. et al Randomized prospective double-blind placebo-controlled
study of dextrose prolotherapy for knee osteoarthritis with or without ACL
laxity, Alern Ther Health Med, 6(2) 68-74, pp.77-80, March 2000
116. Reeves, K.D. "Randomized, Prospective, Placebo-Controlled Double-Blind
Study of Dextrose Prolotherapy for Osteoarthritis Thumb and Finger Joints;"
The Journal of Alter. and Compl. Med.," 6(4): pp.311-320; 2000
117. Reeves, K.D. "Treatment of Consecutive Severe Fibromyalgia Patients
with Prolotherapy," The J. of Ortho. Med., Vol. 16, No. 3, pp.84-89, 1994
118. Riddle, P. Injection treatment, Philadelphia, PA, W.B. Saunders Co.; 1940
119. Roosth, H. Low back and leg pain attributed to gluteal tendinosis:
Orthopedics today; Nov 1991
120. Schultz, L. "A treatment for subluxation of the temporomandibular
joint"; Journal of AMA; Sept 256, 1937
121. Schultz, L. Twenty years' experience in treating hypermobility of the
temporomandibular joints, Amer jour of Surg, Vol 92 Dec.1956
122. Schwartz, R. et al Prolotherapy: A literature review and retrospective
study; J Neurol Orthop Med Surg; 1991
123. Shevelev, A. et al Interosseous receptor system as the modulator of
trigeminal afferent reactions; Worldwide Pain Conference; Pain and
Neuromodulation: the new millennium (hosted by the International and American
Neuromodulation societies); Proceedings of The 9th World Congress: The Pain
clinic; Hosted by the World Society of Pain Clinicians; San Francisco, CA p 34;
715-21/2000
124. Shuman, D. Low back pain, Philadelphia, PA, David Shuman publisher; 1958
125. Shuman, D. Luxation recurring in shoulder; Osteopathic Profession 8:6;
p.11-13; 1941
126. Shuman, D. Sclerotherapy--injections may be best way to restrengthen
ligaments in case of slipped knee cartilage, Osteopathic profession, Mar 1949
127. Shuman, D. The place of joint sclerotherapy in today's practice. Bulletin
of the New Jersey Association of Osteopathic Physicians and Surgeons; Oct 1949
128. Shuman, D. Sclerotherapy: statistics on its effectiveness for unstable
joint conditions, The osteopathic profession, July, pp.11-15 and pp.37-38, 1954
129. Sokov. E. et al Are herniated disks the main cause of low back pain;
Worldwide Pain Conference; Pain and neuromodulation: the new millennium (hosted
by the International and American Neuromodulation societies); Proceedings of The
9th World Congress: The Pain clinic; Hosted by the World Society of Pain
Clinicians; San Francisco, CA p 74; 715-21/2000
130. Spindler, K. et al "Patellar tendon and anterior cruciate ligament
have different mitogenic responses to platelet-derived growth factor and
transforming growth factor b"; J or Ortho research: 14:542-546; 1996
131. Steindler, A. et al: Differential diagnosis of pain low in the back;
allocation of the source of pain by the procaine hydrochloride method, J.A.M.A.,
110:106-113; 1938
132. Vanderschot, L. The American version of acupuncture. Prolotherapy: coming
to an understanding; Am J Acupuncture; 4:309-316; 1976
133. Vanderschot, L. Trigger pints vs. acupuncture points; Am J.
134. Vlemming, A. et al Movement, stability and low back pain: the essential
role of the pelvis, Churchill Livingstone; 1997
135. Wilkinson, H. A. The Failed Back Syndrome Etiology and Therapy, 2nd
Edition, Springer-Verlag; 1992
136. Willard, F. "The lumbosacral connection: The ligamentous structure of
the low back and its relation to back pain as in Proceedings of the Second
interdisciplinary world congress on low back pain, the integrated function of
the lumbar spine and sacroiliac joints; Part I; pp.29-58; San Diego, CA; Nov
9-11, 1995.
137. Yahia, H. et al A light and electron microscopic study of spinal ligament
innervation; Z. mikrosk. -Anat.102; 1989
138. Zoppi, M. et al From intraosseous pain syndrome to osteoarthritis;
Worldwide Pain Conference; Pain and neuromodulation: the new millennium (hosted
by the International and American Neuromodulation societies); Proceedings of The
9th World Congress: The Pain Clinic; Hosted by the World Society of Pain
Clinicians; San Francisco, CA p.412; 715-21/2000.
