PROLOTHERAPY: An Overview

Definition

Prolotherapy is a form of injection treatment. The ligaments of the body are subject to injuries; these are usually termed "sprains" or "strains". The natural healing of the ligamentous sprain is predicated on the inflammatory process. There are occasions when the healing of sprained ligaments is incomplete. The healing reparative process leaves the ligament less strong and less elastic than before the injury. The cycle of healing can be re-provoked without the need of re-spraining the ligament. This re-provocation can be achieved by triggering the inflammatory process through the injection of appropriate medication into the sprained ligament, particularly at its periosteal attachment. This process is called prolotherapy.

Experience with Prolotherapy

The term prolotherapy was coined by an industrial surgeon from Canton, Ohio1 in the 1950's. The concept was initially that of provoking a scar where weakness had occurred in connective tissue. The idea arose from the work of the herniologists of the last century and it was called in those days sclerotherapy2. It goes without saying, in modern times, that scar formation is not propitious. Hackett recognized that there was a disadvantage in creating scars and aimed to provoke the healing process just to the point of achieving hyperplasia of natural connective ligamentous tissues without actual scar formation. As is so often the case in therapeutics, it turned out to be a matter of the dose. A selection of the irritants used in the proliferant solution and their concentration governed the strength of the stimulus. Hypertrophy could be achieved without scarring. The first description of the use of sclerotherapy to an injured ligament hales to a Philadelphia osteopath.3 The significance of the osteopathic contribution will be come apparent presently, as it is within osteopathic circles that experience accumulated in the use of injection therapy for the refurbishment of ligaments, as it is now sometimes called, or reconstruction therapy. In contrast to the postwar style of the allopathic profession, the osteopaths reported on their experience in an informal way, anecdotally and, at best, with retrospective surveys. Even these reports were circulated mostly in osteopathic journals with a small and select readership. Accordingly, the information about prolotherapy, though having a fairly long pedigree, has not gained wide recognition by the medical profession until recently. Cumulatively, however, a fairly wide experience of the use of this technique has accumulated as confirmed by a recent survey4. The teaching has been by what is best described as a network rather than an authoritarian hierarchy university-based style. The authors if this article became aware of this technique in the early 1980's; because it was unfamiliar, skepticism was strong. Nonetheless, the clinical benefit in cases of recalcitrant back pain due to ligamentous injury (more about this later) was salutary; and it is through the experience of finding cures for patients, whose cases were hitherto seemingly hopeless, that a degree of enthusiasm was generated.

A surprise:

The prevailing approach of the management of pain is an anti-approach - to wit, anti-inflammatories and analgesics; it was therefore difficult for us, a rheumatologists and an internists/cardiologists, to adjust our thinking to one of promoting the body's natural healing. Some support came from the realization that the healing of surgical scars is also based on the stimulation of the hyperplasia of the connective tissue and to the laying down of new collagen. After all, surgical scars do not hold indefinitely by suture material alone. After a period of about five years of improving clinical results with these methods, combined with an increasing surprise, not only from our own experience, but also surprised reactions by colleagues, it became apparent that: 1) prolotherapy was a remarkably effective form of treatment in select cases, and 2) there was no independent unbiased confirmation of this impression. We found it impossible to generate enthusiasm in the research-granting establishment for these ideas. There seemed something strongly counter-intuitive about the whole approach. It generated antagonism. Only in recent years, and on the basis of quite extensive research conducted, mostly by our small circle in California, that a better understanding of the role of prolotherapy, its mechanism of action, and the selection of cases has come to pass, dissipating what was a natural skepticism.

Helpful concepts

The space allotted in this article is too short to give the reader a proper understanding of all the concepts necessary to understand the intellectual process of orthopædic medicine (medicine, not surgery) without which it is difficult to make a diagnosis of ligament injuries reliably. One of us (TAD) has written a textbook on the subject which can serve as a reference.5 In order to give the reader an inkling, however, of the process involved, there follows a brief outline of some useful clinical concepts in orthopaedic medicine, the most important of which are the two new paradigms of asymlocation and tensegrity.

Asymlocation

The term asymlocation was introduced in the mid 1980's from the words asymmetric and location. It was recognized that in osteopathic circles somatic dysfunction was a term used promiscuously for asymmetrical alignments within the axial skeleton, whether or not they were associated with clinical pain. The osteopaths have found that through palpation they can quickly identify asymmetric alignment of the vertebrae, pelvis, and even the head and neck, and through manual manipulation restore the alignment towards symmetry. Coincidental with this restoration, there is usually a diminution in pain and, at times, an improvement in various other bodily functions, seemingly through serendipity. A fairly large number of theories have been attached to these observations, and the theories have created the professions, or one might say cults of various manual traditions, including the profession of chiropractic. It is, however, both naive and niggardly to deny the fact that intermittent temporary relief of pain is procured through manipulation in many cases. On the other hand, asymmetries in the alignment of the axial skeleton can often be identified in asymptomatic individuals. From the traditional allopathic perspective, the concept of disease in the absence of symptoms, or obvious dysfunction is paradoxical. We have found substantial pointers to the observation that, with an increasing tendency to asymmetrical alignment, there is a corresponding propensity to pain and dysfunction, though a clear stochiometric relationship between asymlocation and pain is not present. Accordingly, it has been proposed that the term somatic dysfunction be reserved for symptomatic and functional dysfunctions due to mal-alignment and the term asymlocation be used for the (still) asymptomatic ones. We might ask why it is that these asymmetries are so prevalent in the axial skeleton and how it is that, when they become marked, symptoms arise - either locally or at a distance.

Tensegrity:

The word tensegrity was coined by the famous architect Buckminster Fuller from the components of tension and integrity6, and the concept introduced into orthopaedic medicine by an orthopaedic surgeon in the 1980's.7 This concept, which is so helpful in understanding the mechanics of the musculoskeletal system, which is perhaps better called a fascial-ligamentous skeletal system has been reviewed elegantly by Levin8, which reference contains a number of additional useful articles on this subject. The tension members in a tensegrity model, which includes our own bodies, govern form and function in a manner akin to the role of the cables in a suspension bridge, or the down guides in a tent on a campsite. The role of the ligaments in our bodies therefore is not merely to bind structures together, but also that of modulating tension, and affecting the alignment and function of remote parts. Though this concept is, at first encounter, somewhat strange, the physician who can incorporate it into his interpretive armamentarium will find it immensely useful in understanding function and dysfunction of the soft tissues. In summary, it should be said that alterations in tension, e.g., due to a sprain of some ligament or other, can alter the alignment of the sacrum between the ilia or occasionally induce an asymmetry in one or more vertebra. As each vertebra has a degree of movement in three planes, the potential for complexity is large.

Sacral Bracing: A Unique Phenomenon:

A moderately large amount of research has been conducted in the last decade on function, dysfunction, and the role of the human pelvis in locomotion. There are two good references available on the subject9,10, and an additional textbook is in preparation11. A major new understanding of the unique properties of the human sacroiliac articulation is cardinal to this issue12. In a series of elegant research projects at Erasmus University in Rotterdam, Holland, has led to the introduction of the concept of self-bracing at this joint. In contrast to the other synovial joints of the body, the sacroiliac joint has a rough surface, and it turns out that the role of this joint is akin to the role of a clutch in an automobile with shift gears. The ilia toggle slightly with every step we take, bracing on the stance side and releasing stored energy on the swing side. The energy is stored and released, both antigravitationally and through winding of the ligamentous-fascial organ. The ligamentous-fascial organ, in contrast to most other organs of the body, is diffuse, i.e., the tissue is not concentrated in one site, nonetheless, the main concentration of collagenous tissue, for the purpose of this discussion, is in the posterior sacroiliac ligaments just behind the articulation itself. This research not only reconfirms the previously recognized observation that movement of the sacroiliac articulation is normal,13 it elucidated the physiological role of the movement. From this observation, it is only a small step to understanding dysfunction, i.e., the pathological phenomenon of asymmetrical entrapment which, when severe, is a source of additional strain on the ligaments. This is truly somatic dysfunction.

Additional Clinical Tools

What is the effect of excessive pull on a ligament (strain)? It provokes pain. Typically the patient will report first an aching and at times a burning sensation. Additionally, deep structures refer pain to remote sites. This phenomenon of referred pain is familiar to medicine at large. We all recognize the referred pain from the myocardium, the gallbladder, and the other internal organs. Ligament are no exception to this rule. There has, however, been only a passing acquaintance, by the medical establishment , with the patterns of these referrals. The initial research was performed by Kellgren.14 It was, however, Hackett who transferred the recognition of referred patterns of pain to clinical use. The experienced orthopaedic physician has placed in permanent storage in his mind the equivalent of anatomical maps. These consist not only in knowledge of the attachment and location of the ligaments of the body, but also maps of the typical patterns of referred pain. Thus, when a patient presents with a painful condition, the pain diagram is the main clue for the clinician in recognizing the likely pain provocater, often a deep ligament. It is a characteristic of ligaments that the amount of pain, including the referred pain, is proportionate to three things: 1) the severity of the strain, 2) whether there is an underlying sprain in that ligament itself, and 3) the duration. The extent of the stimulus bears a relationship to the extent of the distribution of the referred pain within the relevant dermatome, i.e., the greater the stimulus, the further the pain is referred. Referred pains follow a number of rules. In this context, the word rule is merely a study of a pattern in nature. The pattern, which physicians have discovered, over generations, of the behavior of these pains, is an experiential, empirical science, which is, however, invaluable to the practicing clinician. Readers interested in acquiring these skills may wish to peruse Cyriax's15 textbooks, as well as the other two books alluded to earlier. The term posain has been coined to convey the concept of persistent pain on maintaining one position for a long time. This is a distinct ligament characteristic. Nulliness is the clinical phenomenon of a numb-like feeling a patient has as a referred ligamentous phenomenon, occurring in the same distribution as posain without neurologic deficit. It is a second characteristic of ligaments.

A New Category of Diseases:

It can be seen from this brief summary that we, in medicine, require a new category of diseases in which to house the accumulating information and experience which relates to diseases, injury, dysfunction and treatment of the fascial-ligamentous organ. There is a growing body of knowledge about its anatomy, pathological processes, which are usually dysfunctions of a mechanical nature, and management. The main therapeutic tools are manipulation and prolotherapy. Perhaps this category should be called mechanical disease. The organization of the categories of medicine, which hale to the early part of this century, does not include a mechanical category16. The reason for this omission are unknown. It seems likely, however, that the prevalence of these mechanical problems is increasing. It behooves us, therefore, contemporaneously, to modify the excellent categorization of medicine we inherited from our forebears.

The Evidence for Prolotherapy

In summary, then the main points offered here, as evidence for the effectiveness of prolotherapy, can be categorized thusly: 1) The injection of select chemicals onto collagenous tissue stimulates fibroblasts into to hyperplasia and the laying down of new collagen. This leads to mechanical changes in the ligaments, as evidenced in the experimental animal model17 and also in human tissue18. These histological changes have a mechanical counterpart which is salutary. There is increasing thickness and mechanical strength, and improvement in function of the affected ligaments19. These studies were conducted on rabbit and human knees, respectively, for technical reasons; 2) A recognition of the asymmetry in a normal human population, and its exaggeration in patients with chronic back pain has been confirmed20, and this study also showed a restoration towards symmetry with treatment. 3) The intermittent temporary beneficial role of manipulation has been well established21, but the long-term benefit from the combination of manipulation to restore symmetry, and the use of prolotherapy selectively into the clinically recognized affected ligaments has been confirmed in two separate double-blind controlled studies22,23. This clinical experience has led to an important contribution to the understanding the role of ligaments, particularly in the human pelvis, as organs which store and release elastic energy as part of the efficient mechanism of human walking24. The unique properties of the human sacroiliac articulation, in facilitating this pelvic function, which has been termed transduction,25 has brought forth a deeper understanding of the seeming paradox of the maintenance and recurrence of axial skeletal asymlocation, at times amounting to somatic dysfunction and its permanent correction with prolotherapy; 4) Two independent retrospective surveys have shown the benefit of prolotherapy to last for at least five years26.

Conclusion:

In conclusion, then, prolotherapy has been shown to be a technique with a salutary affect in patients with chronic ligamentous sprains, most characteristically presenting with chronic back pain and at times buttock and leg pain. The diagnosis of the site of the sprain and a clinical decision on the suitability of any particular case for this treatment remains an art based on a thorough grounding in the concepts of orthopædic medicine. The clinical skill, in learning the diagnostic approach of orthopædic medicine also calls for a thorough understanding of anatomy and a meticulous study of referred patterns of pain - a laborious intellectual pursuit. On the other hand, the application of the therapy does not call for complex pharmacological or technological accouterments. The technique of prolotherapy has appealed to a small cadre of clinicians who handle difficult cases of chronic pain and who have developed a high level of clinical skills dependent very little on technology. It should be remembered that ligaments are a tissue which images poorly, and its dysfunction has no laboratory counterpart.

Further Resources:

Addition resources can be found in the footnote. 27

References:

1Hackett GS. Ligament and tendon relaxation treated by prolotherapy. 3rd Ed. Springfield: Charles C. Thomas, 1958.

2Yeomans, FC, ed. Sclerosing therapy, the injection treatment of hernia, hydrocele, varicose veins and hemorrhoids. Baltimore: Williams and Wilkins, 1939.

3Gedney EH. Hypermobile joint. Osteopathic Profession 1937;4:30-31.

4Prolotherapy: A Survey Thomas A. Dorman. J Orthop Med 15:2. 1993.

5Dorman TA, Ravin T, Diagnosis and Injection Techniques in Orthopedic Medicine. Williams & Wilkins. Baltimore 1991.

6Fuller RB. World game lecture series. Philadelphia: Univ Pennsylvania Museum, 1975.

7Levin SM. Proceedings of the 30th annual meeting of the Society of General Systems Research, Philadelphia, Pennsylvania. May 26-30, 1986. 1 ppG14-26.

8Levin SM, The sacrum in three dimensional space. in Prolotherapy in the lumbar spine and pelvis: Spine: State of the art Reviews, Henly & Belfus, Philadelphia, 1996, p381-388. and The importance of soft tissues for the structural support of the body, p357-364.

9The sacrum in three dimensional space. in Prolotherapy in the lumbar spine and pelvis: Spine: State of the art Reviews, Henly & Belfus, Philadelphia, 1996.

10Congress books 1) & 2) Low back pain and its relation to the sacroiliac joint; The integrated function of the lumbar spine and sacroiliac joint. These are the syllabuses of the International congresses on this subject from 1992 and 1995. Available from UCSD Contin Med Ed 0617, 9500 Gilman Dr, La Jolla, CA 92093-0617

11 This is a textbook in progress, based on the above reference. [Churchill Livingstone]

12Dorman, T & Vleeming A, Self locking of the sacroiliac articulation in Prolotherapy in the lumbar spine and pelvis: Spine: State of the art Reviews, Henly & Belfus, Philadelphia, 1996 p407-418.

13Colachis SC, Worden RE, Bechtol CO et al. Movement of the sacro-iliac joint in the adult male: A preliminary report. Archiv Phys Med Rehabil 1963;44.

14Kellgren JH. Observations on referred pain arising from muscle. Clinical Science 1938;3:175-190.

15Cyriax J. Textbook of orthopaedic medicine. 8th ed. London: Bailliere Tindall, 1982.

16Flexner, Abraham. Medical Education in the United States and Canada. A report to the Carnegie Foundation for the Advancement of Teaching, 1910.

17King Liu Y, Tipton C, Matthews RD et al. An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Conn Tiss Research 1983;11:95-102.

18Ongley MJ, Dorman TA, Eek BC et al. Ligament instability of knees: A new approach to treatment. Manual Medicine 1988;3:151-154.

19Klein R, Dorman T, Johnson C. Prolotherapy in back pain. J Neurol & Orthop Med & Surg 1989;10:123-126.

20LaCourse M, Moore K, Davis K, Fune M, Dorman T. A report on the asymmetry of iliac inclination: A study comparing normal, laterality and change in a patient population with painful sacro-iliac dysfunction treated with prolotherapy. J Orthop Med. 12;3; 1990.

21Shekelle, PG, Adams, AH, Chassin, MR, Hurwitz, EL, Brook, RH. Spinal Manipulation for Low-Back Pain. Annals of Internal Medicine, 1992. October 1;117:7. 590-598.

22Ongley MJ, Klein RG, Dorman TA et al. A new approach to the treatment of chronic back pain. Lancet 1987:143-146.

23Klein RG, Eek BJ, DeLong B, Mooney V. A Randomized Double-Blind Trial of Dextrose-Glycerine-Phenol Injections for Chronic Low Back Pain. Journal of Spinal Disorders. 6:1 22-23. 1993.

24Dorman, T.A., Cohen R E., Dasig D., Jeng S., Fischer N., DeJong, A. Energy Efficiency During Human Walking; Before and After Prolotherapy. J Orthop Med 17:1, 1995

25Dorman T, Vleeming A, Self-locking of the sacroiliac articulation. In Henly & Belfus: Spine: State of the art reviews 9(2), May 1995. 407-418.

26Dorman TA. Treatment for spinal pain arising in ligaments - using prolotherapy: A retrospective survey. J Orthop Med. 1990;3.

27The American Association of Orthopaedic Medicine, 90 S Cascade Ave, Suite 1190, >Colorado Springs, CO 80903, USA, Phone: 800-992-2063.

Thomas Dorman, MD.

Wed, Jul 31, 1996