Role of Physical Fitness Training in the

Fibrositis/Fibromyalgia Syndrome

GLENN A. McCAIN, M.D., F.R.C.P.(C) Cardiovascular fitness training has been suggested as a treatment
London, Ontario, Canada
for the fibrositislfibromyalgia syndrome. Thirty-four patients with
fibrositis/fibromyalgfa who met Smythe’s original criteria were ran-
domly assigned to enter either a cardiovascular fitness training pro-
gram or a program consisting only of flexibility exercises. Patients
met in supervised groups three times weekly for a 20-week observa-
tion period. The cardiovascular fitness group underwent gradual
heart rate-elevated training using a bicycle ergometer and achieved
a 29.1 f 24.4 percent increase in peak work capacity at 170 beats
per minute (PWC-170). Patients undergoing flexibility training had a
net reduction in their PWC-170 scores of 4.3 -c 9.4 percent. Patients
in the cardiovascular fitness group had statistically significant im-
provements in the visual analogue pain scale of current pain inten-
sity; total myalgic scores in which pain thresholds at five fibrositic
tender points selected for acceptable intra-rater and inter-rater relia-
bility were measured using a dolorimeter; percentage total body
area affected as measured by self-administered pain diagrams; and
patients’ and physicians’ global assessment scores. Psychologic
profiles as measured by Symptom Checklist-9OR also improved in
the cardiovascular fitness group compared with the flexibility train-
ing group. It is concluded that cardiovascular fitness training is fea-
sible in patients with fibrositislfibromyalgia and that such training
improves subjective measurements of pain-reporting behavior. A
theoretic basis for improvements in pain measurement scales and
psychologic profiles is discussed in light of recent literature.

Voltaire has described the art of medicine as the “ability to keep the
patient entertained while the disease runs its inevitable course.” Nowhere
does this axiom apply more succinctly than to the treatment of patients
with the fibrositis/fibromyalgia syndrome. Patients with a diagnosis of fi-
brositis/fibromyalgia undergo various forms of physical, pharmacologic,
and psychologic therapy. Only recently, however, has substantiation for
one form of intervention, i.e., treatment with the tricyclic antidepressant
amitriptyline, been forthcoming [1,2]. Exercise in the form of cardiovascu-
From the Department of Medicine, Rheumatic Dis-
lar fitness training was suggested as a possible treatment for the fibro-
eases Unit, University Hospital, University of West- sitis/fibromyalgia syndrome by Moldofsky [3]. This seminal observation
ern Ontario, London, Ontario, Canada. This work was prompted by the great difficulty he had in inducing fibrositic tender
was supported in part by a grant from the Canadian points in a marathon runner who, as it happened, was participating in his
Arthritis Society. Requests for reprints should be sleep studies [3]. Fibrositic tender points could not be induced in this
addressed to Dr. Glenn A. McCain, Department of
Medicine, Rheumatic Diseases Unit, University
normal subject after experimental induction of alpha intrusion during his
Hospital, University of Western Ontario, London, usual slow-wave stage four or delta rhythm sleep. Of course, in other
Ontario, Canada N6A 5A5. normal subjects, florid tender points and a nonrestorative sleep pattern

September 29, 1988 The American Journal of Medicine Volume 81 (suppl 3A) 73
SYMPOSIUM ON FlBROSlTlS/FlBROMYALGIA-McCAIN

PRO-OPIOCORTIN ,31K, receptor antagonist, can abolish post-run hypoalgesia

under certain conditions, indicating that strenuous exer-
cise activates the body’s own endogenous opioid system
[8]. Although there is at present conflicting evidence in
humans as to whether beta-endorphin or enkephalin mol-
ACTH I ecules are also naloxone-sensitive, animal studies sug-
gest that exercise-induced analgesia is mediated by the
p - LPH
neural components of the endogenous opiate system [8-
91.
Available data suggest that in response to exercise, in-
creases in serum levels of beta-endorphin or beta-
lypotropin as well as elevated concentrations of opioids in
structures such as the amygdala and hypothalamus re-
sult. Some authors consider the elevated plasma endor-
phin concentrations to only reflect increased tissue levels
igure 7. Schematic representation of pro-opiocortin, the within the central nervous system. This is partly supported
precursor for ACTH and related opiates. by studies showing that intravenous injection of the opioid
beta-endorphin does not affect perception of pain or mood
and does not alter beta-endorphin concentrations in the
developed. Dr. Moidofsky suggested quite adroitly that cerebrospinal fluid [lo]. An alternative explanation for in-
since this man’s Olympian spirit was the only attribute that creased serum levels of beta-endorphin-like immunoreac-
singled him out from his peers, cardiovascular fitness tivity after exercise in that they may simply reflect a role of
training might be favorable in patients with the fibrositis/ opioid systems in the cardiorespiratory and ventilatory
fibromyalgia syndrome. Formal proof of this hypothesis response to exercise since intra-arterial injection of met-
has, however, been lacking. enkephalin inhibits carotid body chemoreceptor dis-
Before presenting preliminary data concerning such an charge, an effect that is blocked by naloxone, and since
exercise program carried out at the University of Western endogenous opiates are found in the brain stem and ca-
Ontario, speculation on the theoretic reasons why cardio- rotid body, two structures responsible for regulation of
vascular fitness training might be expected to benefit pa- ventilation [7]. True modulation of pain sensitivity may
tients with fibrositis/fibromyalgia is in order. therefore depend on tissue levels of endogenous opioids,
specifically those within the central nervous system com-
POSSIBLE MECHANISMS OF ACTION OF STRENUOUS
EXERCISE IN FIBROSITIS/FIBROMYALGIA partment.
These concepts are made more feasible in light of the
Exercise whether administered short-term to unfit persons origin of the naturally occurring opiates. The amino acid
or long-term to fit persons leads to significant alterations in sequence of both methionine enkephalin and beta-endor-
opioid and non-opioid as well as neural and hormonal in- phin are contained in a precursor molecule pro-opiocortin
trinsic pain regulatory systems. For example, strenuous (Figure l), which is synthesized in the hypothalamus, a
exercise leads to predictable increases in serum levels of structure that modulates via its numerous connections
beta-endorphin-like immunoreactivity, ACTH, prolactin, multiple levels of neuronal activity throughout the brain.
and growth hormone [4-71. Furthermore, such alterations These rich connections include the periaqueductal grey of
are associated with decreased pain sensitivity, commonly the brain at which site beta-endorphin may act to modu-
known as “post-run hypoalgesia.” Naloxone, an opioid late ascending and descending pain pathways. A further
interesting notation is that during exercise beta-endorphin
is always co-released with ACTH [4].
TABLE I Central Nervous System Sites for Additional evidence for the role of naturally occurring
Endogenous Opiate Production opiates in the modulation of pain can be seen in Table I,
Opiate Site of Production
which depicts brain-rich areas for each endogenous opi-
oid. Release or activation of these substances during ex-
Pro-opiocortin Neuronal perikarya of hypothalamus ercise might be expected to modulate pain in the fibrositis/
Periaqueductal gray of midbrain
Enkephalin Basal ganglia, limbic system, hypothalamus,
fibromyalgia syndrome. For example, enkephalin in the
substantia gelantinosa of spinal cord spinal cord could conceivably modulate input in the fine
Met-enkephalin Gut, adrenal medulla, autonomic nervous fiber pain afferents, adjusting the “gate” as postulated by
system Melzack and Wall [ll].
Dynorphins Posterior pituitary Exercise might also confer benefits through two addi-
(leu-enkephalin) Spinal cord
tional mechanisms. First, a large body of evidence indi-

74 September 29, 1666 The American Journal of Medicine Volume 61 (suppl 3A)
 SYMPOSIUM ON FlSROSlTlS/FlBROMYALGIA-&CAIN

cates that exercise improves mental status [12]. Ratings TABLE II Group Comparison at Entry
of self-esteem and Beck Depression Inventory scores
Cardiovascular
were significantly improved after cardiovascular fitness Flexibility Fitness
training compared with the ratings of the placebo and no- Group Group
treatment control groups [8,13,14]. Although normal indi- (II = 16) (n = 16)
viduals’ ratings of energy, fatigue, and anxiety are gener-
Age (years) 46 ‘- 8 39-t 10
ally unaffected by exercise, mood as judged by joy and Sex (male/female) 0116 6112
euphoria measurement probes increases. Interestingly, Disease duration (months) 41 ? 41 34 i- 54
reports of enhanced joy and euphoria following exercise Number of tender points 13 ? 1 132 1
can be blunted by treatment with naloxone, indicating Weight loss 1 6
Fatigue 16 16
another link with the endogenous opiate system [8]. Sec-
Altered mood 11 9
ond, exercise may benefit fibrositis/fibromyalgia patients Crying spells 7 7
because of its effects on slow-wave sleep. Although con- Decreased libido 6 5
clusive data are lacking, it appears that exercise results in Sleep difficulty
a delay and decrease of rapid-eye-movement sleep, an Nights per week 4.0 2 1.6 4.8 t 2.1
Hours per night 6.2 k 1.9 2.0 * 2.0
increase in stage two sleep, and a weak decrease in slow- Nonrestorative sleep pattern 16 16
wave sleep latency. Spectral analysis of the electroen- Joint stiffness 14 14
cephalogram shows an increase in the power density of Joint pain 12 15
the delta band in response to exercise, but no such analy- Subjective swelling 10 12
sis has been performed in patients with fibrositis/
fibromyalgia [15]. Helpful effects of strenuous exercise via
its effects on slow-wave sleep are therefore presently
conjectural. program consisted of a 20-week program in which partici-
A word of caution is in order with respect to extrapola- pants met three times weekly. These patients were sub-
tion of the results derived from the exercise studies men- jected to sustained heart rate elevated training via a bicy-
tioned thus far. Strenuous exercise at sustained levels not cle ergometer. Heart rates were maintained in excess of
only induces physiologic changes but may also be re- 150 beats per minute for gradually incremental durations.
sponsible for the development of a stress response. By The flexibility group (placebo group) met at similar inter-
itself, stress could theoretically alter the endogenous opi- vals over a 20-week period. Exercise consisted of flexibil-
ate system, subsequent hormone release, or both. Stress ity maneuvers such that sustained heart rate responses
induction might also be expected to alter the reporting greater than 115 beats per minutes were not attained.
behavior of subjects. In addition, a U-shaped relation be- Table II shows the demographic characteristics of pa-
tween exercise and slow-wave sleep due to the develop- tients in each group at entry. There were no significant
ment of stress at high exertion levels has been previously differences in any categories listed except that due to an
described. Future studies must therefore address the artifact in the randomization process no males appeared
question of stress, which is presently a confounder in clini- in the flexibility group. Outcome measurements were per-
cal studies concerning patients with fibrositis/fibromyalgia. formed at entry and at the end of the 20-week observation
The role that stress plays in the induction or perpetuation period. The following scores were tabulated: (1) A total
of the fibrositis/fibromyalgia syndrome awaits further elu- myalgic score was computed using a g-kg Chattillon
cidation. dolorimeter. The device and technique were standardized
in a preliminary trial [l] and can be used to measure pain
A RANDOMIZED CLINICAL TRIAL OF EXERCISE IN thresholds at five designated fibrositic tender points. A
FlBROSlTlS/FlBROMYALGIA maximum score of 360 kg is possible. However, scores of
During the last three years, we have entered patients from 300 f 48 kg were noted in our normal control population.
our clinics at University Hospital, London, Ontario, into a Our first 64 unselected consecutive patients with
clinical trial that is studying the effects of a double-blind fibromyalgitifibrositis had scores well beyond two
supervised exercise program on the manifestations of the standard deviations of the values of normal subjects at
fibrositis/fibromyalgia syndrome. Preliminary results from 150 * 53 kg (Figure 2). (2) A visual analogue pain score
this trial are now available. was ascertained whereby patients indicated their current
Thirty-four patients fulfilling Smythe’s criteria for primary pain intensity on a line 100 mm long. Data are expressed
fibrositis/fibromyalgia were randomly assigned to enter in millimeters with lower numbers indicating lesser de-
either a cardiovascular fitness training program or a pla- grees of pain. (3) A pain diagram was reported by each
cebo exercise group consisting primarily of flexibility ma- subject. Diagrams showed the total body area affected by
neuvers. Both patients and assessors were blinded to pain and were used to express the percent of body area
group membership. The cardiovascular fitness training affected by fibromyalgia complaints.

Geptember 29, 1988 The American Journal of Medicine Volume 81 (suppl 3A) 75
SYMPOSIUM ON FIBROSITIS/FIBROMYALGIA-McCAIN

TABLE III Comparison of Outcome Measures in

360’
Each Group at Entry

Flexibility Cardiovascular
Gruip Fitness Group p Value

300 Initial total myalgic 154.0 ? 92 124.0 k 95 NS

score
Initial visual analogue 58.5 ?I 15 68.6 2 15 NS
pain score
250 Initial pain diagram 10.4 2 6.9 14.1 i- 8.0 NS
Initial PWC-170 664.5 ? 182.9 727.2 ? 248.9 NS
i+ NS = not significant.
s
0-J
” 200.
3
9
2 TABLE IV Summary of Study Results
1 150.
c Cardiovascular
P Flexibility Fitness
Gmup Group
100. PWG-170 (percent) -4.3 k 9.4 29.1 - 24.4
0 Total myalgic score
(kg/m’)
14.7 k 40.6 44.4 2 74.6

Total myalgic score 7.0 k 23.3 72.9 k 129.5

50- 2 (percent change
from baseline)
%3 Visual analogue pain -0.7 ‘- 21 -23.2 i 30.6
score (mm)
Q
I Pain diagram -0.12 ? 3.2 TBA -1.26 2 13 TBA
FI BROMYALGIA NORMAL (percent)
PATIENTS CONTROLS Pain diagram 0.6 L 40 22.7 2 114.4
(percent change
igufe 2. Total myalgic scores of 64 consecutive patients
from baseline)
with fibrositislfibromyalgia syndrome and normal control
subjects. ‘TBA = total body area.

The effects of each exercise program on cardiovascular
fitness was assessed by a simple two-stage heart rate
analysis known as PWC-170, which predicted the peak
work capacity at 170 beats per minute for each subject.
Table III shows no significant differences in any of these
variables between subjects randomly assigned to the car-
diovascular fitness or flexibility groups at entry. Subjects
in the cardiovascular fitness group had significantly more
pain-reporting behavior than did those in the flexibility
group. Higher PWC-170 values in the cardiovascular fit-
ness group at entry reflect the greater number of males in
this group, but this difference did not reach statistical sig-
nificance.
Table IV summarizes our results to date. Patients in the
flexibility group showed a mean decrease in cardiovascu-
lar fitness of 4.3 percent, compared with a net increase of
29.1 percent in the heart rate-elevated or cardiovascular
fitness group. This indicates that it is feasible to obtain
enhanced cardiovascular fitness in patients with fibrositisl
fibromyalgia using the techniques described. Only two of
18 patients in this group failed to increase their PWC-170
scores by 10 percent, an increase that we believe is indic-
ative of enhanced cardiovascular fitness. These subjects’
scores are, however, included in our statistical analysis.
The total myalgic score improved an average of 72.9
percent in the cardiovascular fitness group but only 7.0
percent in patients undergoing flexibility training. Similarly,
visual analogue pain scores improved by 23 percent in the
cardiovascular fitness group, whereas they improved only
7 percent in the flexibility group. This is also reflected in
the pain diagram scores in which 22.7 percent improve-
ment was noted in the cardiovascular fitness group versus
a 0.8 percent improvement in the flexibility group.
Although these results are preliminary and the statisti-
cal analysis is incomplete, the study does show that cardi-
ovascular fitness training improves objective measure-
ments of pain in the fibrositis/fibromyalgia syndrome. It
remains to be seen whether such a program can be ad-
ministered to larger numbers of fibrositic patients. It opens
up new considerations as to which of the many physio-
logic alterations induced by strenuous exercise is respon-
sible for these effects, and it generally supports the con-
cept that the fibromyalgia syndrome may be a pain modu-
lation disorder.

76 September 29, 1966 The American Journal of Medicine Volume 81 (suppl 3A)
 SYMPOSIUM ON FlBROSlTlS/FlBROMYALGIA-McCAIN

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