TREATMENT OF CONSECUTIVE SEVERE FIBROMYALGIA PATIENTS WITH PROLOTHERAPY

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TREATMENT OF CONSECUTIVE SEVERE FIBROMYALGIA PATIENTS WITH PROLOTHERAPY

K DEAN REEVES MD

Kansas City,Kansas

_http://www.prolotherapy.com/articles/reeves.htm_

(http://www.prolotherapy.com/articles/reeves.htm)

(http://www.prolotherapy.com/articles/reeves.htm)

ABSTRACT

The potential of tendon and ligament triggers as primary nociceptors in

fibromyalgia led to treatment of primary fibromyalgia patients with tendon and

ligament strengthening injection. Trigger injection of ligament and tendon with

proliferant (TILT therapy or prolotherapy) offers the advantage of creating

increased strength of the connective tissue in the region of injection as

well as affecting the pain cycle. Reduction in pain levels and increased

functional abilities were seen in excess of 75 % of patients with severe

fibromyalgia in this study. The implications of this for further study are

considered.

INTRODUCTION

The search for *central factors* in the cause of fibromyalgia has revealed

evidence of possible alteration of pain modulation in the body such as a

decrease in circulating serotonin and possibly antibodies that block serotonin

receptors. 27,39 Evidence has also been found for central factors affecting

soft

tissue homeostasis. (Possible glucocorticoid deficiency or deficient

production of growth hormone related factors. 3,14,24) Search continues for the

primary nociceptor in fibromyalgia. It is notable that the classical tender

points in fibromyalgia are over tendon and ligament insertions. Semi-elastic

tissues are generally recognized to be the sites of acute damage in sprain and

strain. 35 Tendon and Ligament attachments to periosteum have the lowest pain

threshold of any deep somatic structure. 4 Inman and Saunders reported

stimulating periosteum in a variety of ways including pressure, and elicited

severe

referred pain to muscles or bony prominences in the referral zone in

reproducible patterns. 23 De Valera, Gorrell, Hackett, Kelgren, Kraus, Leriche

and

Travell have all described referral pain from tendinoligamentous structures,

with patterns of referral most meticulously set out by Hackett.

8,12,15-22,25,29,40,41,42 Tendon or ligament laxity or weakness has been

proposed to cause

chronic nociception via inadequate skeletal support, intermittent stretch of

fixed-length sensory fibers, or development of myofascial trigger points. 19,35

The premise of this study is that weak or lax tendons or ligaments are

potential nociceptors in fibromyalgia and that this is potentially a

correctable

nociceptor source.

Prolotherapy involves injecting an area of ligament or tendon laxity or

weakness with a solution that stimulates fibroblast proliferation. The goal of

proliferation therapy is to restore normal connective tissue length and

strength in the affected area, and in so doing to restore adequate skeletal

support

and eliminate sources of myofascial trigger perpetuation. 2 Borden

demonstrated the ability of a simple dextrose solution in 12.5% concentration or

more

to create a prompt inflammatory reaction. 6 The simple dextrose solution is

thought to create irritation by an osmotic gradient. Cells in the area lose

water, and desiccate to the point of an injury response. Animal studies have

shown a 40% increase in diameter and strength of injected tendons compared to

contralateral tendons. 17,32 Changes persisted more than 12 months post

injection and were not dependent on any difference in exercise levels of the

animals. Human studies have demonstrated collagen fiber diameter increases and

increased cellularity on biopsy of injected areas. Disability, range of motion,

and pain levels all improved significantly in patients injected after 5 or more

years of chronic pain. 26 In human knees with reproducible ligamental laxity

as measured by a computerized knee analysis device, a statistically

significant reduction in ligamental laxity was demonstrated with a P value less

than

0.05. 37 Randomized double-blind control studies with saline injected controls

have demonstrated statistically significant improvements in low back pain

and disability rating in treated patients compared to controls. 28,36

METHOD

Patient Population

Consecutive patients with severe fibromyalgia were treated with

tendon/ligament strengthening injection. The fibromyalgia was sufficiently

severe in each

case that all the patients desired intervention trial. All patients had

experienced continuous upper body, back, and lower body pain for more than 6

months, with average duration 7 years and 10 months. Tender points were present

in at least 7/9 classic regions on both sides of the body. Functional

questionnaires indicated that 37% had regular narcotic intake, sexual function

was

limited in 48%, arm numbness made handling small objects difficult in 55%, 70%

of patients had to lay down during the day due to pain, lifting arms overhead

increased pain in 70% of patients and bending, twisting and squatting

frequently was intolerable to more than 80% of the patients. Awakening from pain

averaged 3.1 times per night. Sitting tolerance was 33 minutes; standing

tolerance 27 minutes; light work tolerance 45 minutes; heavy work tolerance 19

minutes; and writing tolerance l7 minutes.

Solution used

The solution used was made by combining 3cc of 50% dextrose with 2cc of 1 %

xylocaine (lignocaine) and 7cc of benzyl alcohol type bacteriostatic water,

making a dextrose concentration of was 12.5%.

Typical first session

There are several *methods* of prolotherapy, and two representative texts

can be referenced for details. 9,22 Because of the very diffuse number of

painful entheses, the method of injection was the meticulous one of Hackett.

22,38

A typical comprehensive first injection session for upper and lower body

included the following numbers and sites of injections, with 0.5 cc to 0.75cc

injected at each site, assuming both sides of the body treatment in almost all

potential injection sites. Semi-spinalis, splenius and rectus capitus

insertions on base of skull (24); cervical facet ligaments (14) ; cervical

intertransversarii (28); posterior superior trapezius insertions on back of

clavicle

(8); lateral costotransverse ligament attachment to ribs (14); infraspinatus,

teres major and minor attachments to scapulae posteriorly (28); scalene

attachments ant and post tubercles (16); subscapularis, biceps and pectoralis

insertions on anterior portion of humerus (16); common extensor attachments at

elbow(6); lumbar intertransversarii (10) ; lumbar facets (10); lumbosacral

junction (6 with several needle redirections) ; Crest of ilium (6); iliolumbar

ligament (4 with several needle redirections); SI ligament (6 with several

needle redirections); gluteus maximus, medius and minimus insertions on iliac

bone (30); deep articular ligaments of hip (6 with several needle

re-directions); external rotator and gluteii attachments posterior trochanter

(24); distal

adductor attachments knee (2); hamstring attachments in anserine bursa (16).

It can immediately be seen that this is a time consuming and exacting

procedure when done comprehensively. The volume of solution used can be as much

as

200cc with treatment, but the concentration of Xylocaine in the solution of

less than .2%, coupled with the length of the procedure causes no problems in

terms of anesthetic toxicity.

Sedation

Oral vistaril (hydroxyzine) was used for nausea prophylaxis to avoid rare

anaphylaxis with compazine. An anesthetic gun was used to numb the skin in all

patients who preferred it to the needle insertion sensation. Intravenous

demerol (pethidine) was used as the exclusive sedation except for those with

demerol allergy or with prolonged nausea after demerol use. Valium (diazepam)

was

added or used exclusively when demerol was not feasible as a sole agent.

Continuous oximetry was used with an office attendant present to ensure

oximetry

values above 87% and regular breathing patterns. Narcan (naloxone) was

immediately available. It is important to note that demerol should be titrated

in

25-50mg increments for first one to two sessions. Careful record keeping

should allow determination of ideal amounts for sedation by session. 3 Oximetry

or close observation of breathing patterns was considered particularly

critical with use of 40mg of demerol or more in the elderly or 75mg or more in

the

young. Demerol was titrated with first the first one to two sessions to

determine the patients' reaction and careful records kept as to ideal amounts

for

future reference. Note that the reason for significant amounts of demerol was

the substantial time period required for comprehensive injection.

Injection follow-up

Because of healing cascade length of 8 weeks, follow-ups were scheduled at

that interval in general, though other pain areas may have been treated in the

interim. At follow-up, pain areas and palpation determined areas of

injection. All sore areas to palpation were not reinjected, but rather

potential

trigger areas for current pain were addressed. Patients received an average of

3.5 injection sessions to any particular pain region.

Questionnaire use

Questionnaires were sent out to all patients who had received one or more

treatments, with the first treatment occurring at least 6 months before

questionnaire mailing. This questionnaire asked about pain levels pre- and

post-

treatment by body region. Other questions requested assessment of overall

frequency and intensity of pain, and tolerance of sitting, standing, walking,

sleeping, light work, and heavy work. Patients were also asked to compare

tendon/ligament strengthening injection to other treatments they had received

in the

past, and asked about complications. If questionnaires were not returned,

follow-up 'phone contact confirmed if one was received, and the patient was

encouraged to return the questionnaire. 'Phone interviews were decided against

to

avoid leading the answers. 31 of 40 consecutive fibromyalgia patients

returned follow-up questionnaires, or 78% of the patients so treated.

RESULTS

Table 1 depicts the average pain levels of the 31 patients by area, using a

10 point scale with '10' the worst pain imaginable and '0' being no pain at

all ever. The 16 regions chosen were rated at 4.86 out of 10 pre-injection and

3.30 post-injection for a reduction of 32.1 %. All regions of the body were

noted to have less average pain after injection.

Region

Average Pain before RX

Average Pain after RX

Head

5.81

3.77

Neck

7.00

4.45

Front of Shoulder

4.52

3.03

Top of Shoulder

5.68

3.55

Back of Shoulder

7.03

4.26

Elbow/Forearm

3.52

2.26

Wrist/Hand

3.00

2.00

Upper Back

6.23

4.03

Front of Chest

4.10

2.81

Mid Back

6.71

4.77

Low Back

6.77

4.90

Buttock/Hip

5.42

4.26

Thigh

3.94

2.81

Knee/Calf

3.10

2.42

Ankle

2.19

1.81

Foot

2.68

1.7

Whole Body (average of above)

4.86

3.30

Table 1

Pain before and after tendon/ligament strengthening injection (prolotherapy)

Table 2 depicts the functional outcome of injection. 21/31 patients

indicated their pain frequency was better, much better or gone, and 18/31

indicated

their pain intensity was better, much better, or none. The questionnaire asked

for an explanation of *worse* or *much worse* responses, with reasons given

of stress in 3/5, work in 2/5, needing to follow-up with no insurance in 2/5,

and don*t know in 1/5. Two of these patients had only one treatment.

Improvement in sitting, standing, walking and sleeping ability in minutes was

noted

to be about the same for each. Of particular interest from a functional point

of view was that of the 30 patients indicating problems with tolerating

light work,18 indicated they were better or much better at tolerating light

work,

and 2 indicated they tolerated light work less. The results were not so

favorable for heavy work, with 9 indicating they tolerated heavy work better

and

6 less. The 6 indicating they were worse again gave *stress*, *work*, *had to

stop treatment*, or *don't know* as the reason. Levels of Pain/Ability A:

never a problem B: back to normal C: much better D: better E: same

F: worse G: much worse A B C D E F G Frequency of Pain 0 1 8 12 5 3 2

Intensity of Pain 0 1 6 11 8 2 3 Sitting Ability 0 2 5 10 10 4 0 Standing

Ability 0 2 3 13 6 6 1 Walking Ability 1 3 2 12 6 6 1 Sleeping Ability 1 2

4 6 13 4 1 Light Work Ability 1 1 5 12 10 1 1 Heavy Work Ability 0 1 1 7

16 4 2

Table 2

Functional results of tendon/ligament strengthening injection;

changes post injection

Table 3 provides results when patients were asked to compare the outcome of

tendon-ligament strengthening injection with any previous treatments they had

received. They were given a series of statements to choose from, and asked

to pick the one that described their opinion. Note that all patients (other

than those unable to take time off work for therapy) were offered 6-9 sessions

of physical therapy for postural exercise, stretching and massage

instruction, instruction in proper heat use, encouragement to walk, and

amitriptyline or

flexeril. 22/31 had previously received physical therapy; 14/31 had

previously received manipulation; 6/31 acupuncture; and 17/31 massage. Of the

31

patients, 12 indicated that it was the only really effective treatment they had

received, and 23 of 31 indicated it was more helpful than any past treatment.

Patients were asked to indicate their status with respect to future

treatment, and were given several responses to choose from.

Only really effective treatment was injection

12/31

Injection was much more effective than other treatments I have received

8/31

Injection was helpful but effects did not last

5/31

Injection was more effective than other treatments

3/31

Injection was as helpful as any other treatment

1/31

Injection not as helpful as other treatments

1/31

Injection not helpful

1/31

Table 3

Comparison of prolotherapy with other treatments previously received

Table 4 displays their answers. Particularly notable was that of those not

desiring follow-up at the time of the questionnaire mailing, 6 were better or

plateau, two did not specify, and only one thought the treatment was too much

to go through. Despite the use of sedation and skin anesthesia with a jet

gun, there is no way to truly make this treatment pleasant. Patient tolerance

of treatment was impressive, however, in that only l/3l stated they were not

continuing treatment because it was too much to go through. Patients did need

substantial support not only during the treatment sessions which averaged 1

hour and 30 minutes in length, but also between treatments with questions that

arise. The implication is that this treatment at this level of intensity

would be impractical for the busy clinician.

Follow-up planned because my original pain needs to get better

21/31

I am enough better and don't need treatment now

3/31

No treatment planned. I am as good as I think I will get

2/31

No follow-up planned because I am all better

1/31

Follow-up planned because new pains have developed

1/31

Insurance or workman's compensation does not cover treatment

1/31

Treatment is too much to go through

1/31

I am not better. I don’t think treatment will help

0/31

Other (Non specified)

2/31

Table 4

Follow-up plans post prolotherapy

When patients were asked if they had any significant complications or side

effects from treatment they answered as in Table 5. Note that, of what would

truly be considered a complication, one had superficial phlebitis of a vein

injected for sedation purposes and one had a spinal headache. It is important

to warn patients of temporary new pains, variable pain periods after

injection, small marks from anesthetic gun if it is used, nausea, and, if

injections

are given over posterior rib attachments, pneumothorax. In this practitioner's

experience with this particular injection method a symptomatic pneumothorax

has occurred approximately once each year when injections over posterior

thorax average 100 or more per day - given the large numbers of injections in

each session could be significantly high if the clinician is not trained in

angles to use, lengths of needles to use, and depths of injection. Injections

of

arterial structures are rare since injection never occurs unless bone is

touched, and aspiration occurs in critical areas such as the neck laterally.

The

amount of anesthetic injected at any one time is substantially smaller than

the smallest amount ever shown to cause a seizure or cessation of respiration,

even with direct vertebral artery instillation. 5 Nerve damage has never

been reported with use of dextrose instillation and generally thin caliber

needles used. If electrical sensation occurs, however, the needle should be

repositioned.

New pains for a while

11

Not specified

5

Vein irritated from sedative agents

1

Longer recuperation after some treatments

1

Spinal headache

1

Pain after injection

1

Appearance (Small marks from anesthetic gun)

1

Nausea for several days

1

Table 5

Side effects/complications of prolotherapy in severe fibromyalgia syndrome

A complicating factor in follow-up exam of these patients is that the number

of tender points diminished as symptoms improved. Note that the 'tender

points' were often injected during the course of treatment. (i.e. common

extensors elbow, distal adductors knee, cervical paraspinals, costotransverse

ligaments, upper trapezius).

DISCUSSION

There is an accumulating body of evidence for peripheral soft tissue changes

in fibromyalgia. An example would be strong evidence for an increase in

tissue compliance and reactive skin hyperemia in fibromyalgia. 3 Searching in

skeletal muscle has not yielded consistent findings on biopsy, though changes

of

degeneration are often seen. 10 Bennett postulated that a defect in repair

processes after micro or macrotrauma in fibromyalgia may prevent resolution of

such injuries, with development of chronic pathology. 3 Recent evidence has

indicated that Somatomedin C (a growth hormone-related factor important in

musculoskeletal homeostasis) is deficient in fibromyalgia patients. 3 Note that

growth hormone-related factors are secreted primarily during stage IV sleep

and that stage IV sleep disturbance by alpha wave intrusion is characteristic

of fibromyalgia. 3,33,34 Jacobsen et al's finding of somewhat lower levels

of Type III procollagen in serum in fibromyalgia patients is interesting, in

that procollagen is a critical precursor in the healing of connective tissue.

24 The healing cascade after semi-elastic tissue damage is critical in making

the ligament/tendon sufficiently tight and thick to continue normal

function, but is time-limited to 2-3 months after injury, and is dependent on

adequacy of fibroblast density, procollagen deposition, maturation to collagen,

cross band formation with shortening of the tendon and ligament laxity. 7

Injection of tendon and ligament triggers, since it includes anesthetic, may be

considered capable of having acupuncture effects or effects on breaking the

pain

cycle; but acupuncture points were not specifically treated in this study,

and trigger injection with anesthetic alone has not been convincingly

demonstrated to be effective in allowing a sustainable improvement in function

or pain

level in the presence of whole body pain of fibromyalgia.

With respect to the study patients, there can be little doubt that they have

severe fibromyalgia - given sitting and standing tolerance less than 30

minutes, having to lay down during the day due to pain in 70%, light work

tolerance only 45 minutes, and intolerance of bending, twisting, and squatting.

In

addition the average duration of whole body pain of 7 years 10 months suggests

strongly that spontaneous remissions to marked degree would not be expected

in this population and that spontaneous worsening would be at least as

likely. This is supported by Ledingham's long term study showing 97% of

patients

persisting with symptoms, 85% still fulfilling criteria after 4 years post

onset, with 60% rating their symptoms as worse and 26% better than at

presentation 4 years post onset. 30 His study included fibromyalgia patients

without

severe functional impairment at onset of study. Results in this study of

resuming the healing cascade in areas of proposed ligamental laxity indicate 33%

pain reduction. This can mean that the treatment is only partially effective,

that there are perpetuating factors preventing full resolution, or that the

critical ligamental laxities were not addressed.

Further studies are under way using various combinations of ligaments.

Functional status after treatment indicates improvability of pain frequency and

intensity, sitting, standing, walking and sleeping. Since for most fibromyalgia

patients a key goal is to keep working with their disease, 18/31

experiencing improvement in light work ability and 2/31 a worsening is of

particular

functional significance. The rating of this treatment by 22/31 as better than

any previously received over the average 7 years of fibromyalgia and less

effective in only 2/31 is encouraging for a potential unique role of this

treatment in refractory fibromyalgia.

SUMMARY

The improvements in pain levels and functional ability after injection is

supportive of tendon and ligaments being a major source of symptomatology in

fibromyalgia. In order to make this treatment more practical further studies to

determine the relative importance of various ligament/tendon nociceptors in

fibromyalgia will be important. In addition it is hoped that this study will

encourage basic science investigators to further research homeostasis of

connective tissue in fibromyalgia, as even microtrauma of daily living in the

presence of impaired homeostasis may sufficient to explain onset of symptoms.

The tendency of ligaments and tendons to refer pain and numbness in

non-radicular patterns and to inhibit muscular function to create such symptoms

as

give-way weakness and a feeling of non-specific fatigue could go a long way in

explaining why physicians tend to mis-diagnose these patients as having

somatisation disorder. The lack of evidence for primary psychiatric disorders as

the

cause for fibromyalgia has been set out in the literature in a convincing

fashion, but until the symptomatology of ligament and tendon pathology is more

widely recognized, the symptoms of fibromyalgia will remain an enigma to most

practicing physicians. 1

REFERENCES

1 Ahles TA, Khan SA, Yunus MB et al Psychiatric status of patients with

primary fibromyalgia, patients with rheumatoid arthritis, and subjects without

pain: a blind comparison of DSM-III diagnoses. Am J Psychiatry 1991

148(12):1721-1725

2 Banks AR A rationale for prolotherapy J Ortho Med 1991 3:54-59

3 Bennett RM, Clark SR, Campbell SM. Burckhardt CS Low levels of somatomedin

C in patients with the fibromyalgia syndrome: a possible link between sleep

and muscle pain Arthritis Rheum 1992 35(10)1113-1116

4 Bonica JJ Anatomic and physiologic basis of nociception and pain In Bonica

JJ (ed): The Management of Pain 2nd Ed Philadelphia, Lea & Febiger 1990 p35

5 Bonica JJ Anatomic and physiologic basis of nociception and pain In Bonica

JJ (ed): The Management of Pain 2nd Ed Philadelphia, Lea & Febiger 1990

p1944

6 Borden AG: Some investigational aspects of prolotherapy in Animals and Man

Paper Presentation llth Annual Clinical Symposium of the Prolotherapy

Association June 16 1968 Bellevue Hotel, San Francisco, Ca

7 Clark RAF, Henson PM The molecular and cellular biology of wound repair

New York, Plenum Press 1988

8 de Valera E, Laftery H Lower abdominal and pelvic pain in women In Bonica

JJ, Albe Fessard D (eds) Advances in Pain Research and Therapy Vol 1 New

York, Raven Press 1976 pp 925-936

9 Dorman TA, Ravin TH Diagnosis and Injection Techniques in Orthopedic

Medicine Baltimore, Williams and Wilkins 1991

10 Drewes AM, Andreasen A, Schroder HD, Hogsaa B, Jennum P Pathology of

skeletal muscle in fibromyalgia: a histo-immuno-chemical and ultrastructural

study Br J Rheumatol 1993 32 (Suppl 6):479-483

11 Goldenberg DL Psychological symptoms and psychiatric diagnosis in

patients with fibromyalgia Jnl Rheumatol 1989 16(Suppl):127-130

12 Gorrell RL Troublesome ankle disorders and what to do about them

Consultant 1976 16:64-69

13 Granges G, Littlojohn GO A comparative study of clinical signs and

fibromyalgial fibrositis syndrome, healthy and exercising subjects. J Rheumatol

1993 20(2):344-351

14 Griep EN, Boersma JW, de-Kloet, ER Altered reactivity of the

hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome J

Rheumatol 1993

20(3):469-474

15 Hackett GS Joint stabilization through induced ligament sclerosis Ohio St

Med Jnl 1953 49(10):877-884

16 Hackett GS Shearing injury to the sacroiliac joint Jnl Intnl Coll Surg

1954 22(6):631-642

17 Hackett GS Ligament and Tendon RelaxationTreated by Prolotherapy 3rd Ed

Springfield, Charles C Thomas 1956 pp27-36

18 Hackett GS Ligament and Tendon Relaxation Treated by Prolotherapy 3rd Ed

Springfield, Charles C Thomas 1956 pp94-100

19 Hackett GS Prolotherapy in whiplash and low back pain Postgrad Med 1960

27(2):214-219

20 Hackett GS Prolotherapy for sciatica from weak pelvic ligaments and bone

dystrophy clinical medicine 1961 8(12):2301-23161961.

21 Hackett GS, Huang TC, Raftery A Prolotherapy for headache 1962 Headache

2:20-28

22 Hackett GS, Hemwall GA, Montgomery GA Ligament and Tendon Relaxation

Treated by Prolotherapy 5th Ed Oak Park, III Gustav A Hemwall 1991

23 Inman VT, Saunders JB Referred pain from skeletal structures J Nerv Ment

Dis 1944 99:60-667

24 Jacobsen S, Jensen LT, Foldager M, Danneskiold- Samsoe B Primary

fibromyalgia: clinical parameters in relation to serum procollagen Type III

aminoterminal peptide Br J. Rheumatol 1990 29:174-177

25 Kelgren JH Observations on referred pain arising from muscle Clin Sci

1975 3:280-281

26 Klein RG, Dorman TA, Johnson CE Proliferant 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

1989 10(2):141-144

27 Klein R, Bansch M Berg PA Clinical relevance of antibodies against

serotonin and gangliosides in patients with primary fibromyalgia syndrome

Psychoneuroendocrinology 1992 17(6):593-598

28 Klein RG, Bjorn CE, DeLong B, Mooney V A randomized double-blind trial of

dextrose-glycerine-phenol injections for chronic low back pain J of Spinal

Disorders 1993 6(1 ):23-33

29 Kraus H Clinical treatment of back and neck pain New York, McGraw Hill

1970 pp95,107

30 Ledingham J, Doherty S, Doherty M Primary fibromyalgia syndrome: an

outcome study. Br J Rheumatol 1993 32(2j:139-142

31 Leriche R Des effetes de I'anesthesia a la novocaine des ligaments et des

insertions tendineuses peri-articulaires dans certaines maladies

articulaires et dans vices de position fonctionnels des articulations Gazette

des

Hopitaux 1930 103:1294

32 Liu YK, Tipton CM, Mathes RD, et al An in-situ study of the influence of

a sclerosing solution in rabbit medial collateral ligaments and its junction

strength Connect Tis Res 1983 11:95-102

33 Moldofsky H, Scarisbrick P, England KR, Smythe IH Musculoskeletal

symptoms and non-REM sleep disturbance in patients with 'fibrositis syndrome'

and

healthy subjects Psychosom Med 1975 37:341-351

34 Moldofsky H, Scarisbrick P Induction of neurasthenic musculoskeletal pain

syndrome by selective sleep stage deprivation Psychosom Med 1976 38:3-44

35 O'Donoghue DH Principles in the management of specific injuries ln

O'Donoghue DH (Ed): Treatment of Injuries to Athletes 4th Ed Philadelphia, W.B

Saunders 1984 p51

36 Ongley MJ, Dorman TA, Klein RG, et al A new approach to the treatment of

chronic low back pain Lancet 1987 July 8551 (2):143-146

37 Ongley MJ, Dorman TA, Esk BC, et al Ligament instability of knees: a new

approach to treatment Manual Medicine 1988 3:152-154

38 Reeves KD Technique of Prolotherapy In Ted Lennard (Ed) Procedures in

Physical Medicine and Rehabilitation Malvern, PA, Lea and Febiger 1994 pp

pending

39 Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA et al

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in

patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992 19(1 ):104-109

40 Travell J Pain Mechanisms in Connective tissue In Ragan C (Ed) Connective

Tissues Transactions of the 2nd Conference new York, Josiah Macy Jr

Foundation 1952 pp96-102,105-109,111

41 Travell JG, Simons DG (Eds) Myofascial Pain and Dysfunction: The Trigger

Point manual Baltimore, Williams and Wilkins 1983

42 Weiser HI Semi-membranosus insertion syndrome: a treatable and frequent

cause of persistent knee pain Arch Phys Med Rehabi) 1979 60:317-139

Address for correspondence:

K Dean Reeves MD

155 S. 18th St, Suite 180

Kansas City, KS 66102