|
The Journal of Neurological
and Orthopadic Medicine and Surgery, Vol. 12. No. 3. 1991
Prolotherapy: A Literature
Review and Retrospective Study
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
manipulation 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 end of the
Prolotherapy 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.
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 (Table 1).
Table 1. Relief obtained in 43
patients after a series of prolotherapy injections (three injections, once
every other week).
No. Of
patients
0% 33%
50% 66%
75% 99%
(43 total)
Relief Relief
Relief Relief Relief
Relief
Reported
relief
3
1 4
4 11
20
Recurrence
(10 total)
----- 1
1 2
2 4
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 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 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.
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
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
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)
|
