Pain 109 (2004) 497–499
Exercise lowers pain threshold in chronic fatigue syndrome
Alan Whitesidea, Stig Hansena, Abhijit Chaudhurib,*
aDepartments of Clinical Physics, Institute of Neurological Sciences, South Glasgow University Hospitals NHS Trust, Glasgow, UK
bDepartment of Neurology, Institute of Neurological Sciences, South Glasgow University Hospitals NHS Trust, 1345 Govan Road, Glasgow G51 4TF, UK
Received 17 December 2003; received in revised form 17 February 2004; accepted 23 February 2004
Post-exertional muscle pain is an important reason for disability in patients who are diagnosed to have Chronic Fatigue Syndrome (CFS).
We compared changes in pain threshold in ﬁve CFS patients with ﬁve age and sex matched controls following graded exercise. Pain
thresholds, measured in the skin web between thumb and index ﬁnger, increased in control subjects with exercise while it decreased in the
CFS subjects. Increased perception of pain and/or fatigue after exercise may be indicative of a dysfunction of the central anti-nociceptive
mechanism in CFS patients.
q 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Keywords: Chronic fatigue syndrome; Exercise; Pain threshold
from all subjects. All pain related treatment and anti-
depressants with analgesic effects were withdrawn 48 h
Chronic Fatigue Syndrome (CFS) is a debilitating
before testing and subjects were asked not to undertake
condition that is characterised by chronic fatigue, impair-
physical exertion for 24 h prior to the investigation.
ment of short-term memory and musculoskeletal pain
The exercise consisted of three 5-min periods on a
(Fukuda et al., 1994). The cause of CFS is not known.
treadmill, set to a speed of 5 km h21, with an increasing
Pain is considered to be an important reason for disability
incline of 5, 10 and 158 at each stage of the graded exercise
in CFS. Patients with CFS experience muscle pain and post-
test. Pain thresholds were measured in the skin web between
exertional malaise following sustained exercise. The mech-
thumb and index ﬁnger using an Algometer designed
anism of increased muscle pain after exercise in CFS is not
in-house. A force is applied on both sides of the skin web
known but is considered to be an important reason for low
with a pair of tweezers. The area of contact is 16 mm2 and
compliance with graded exercise therapy (Chaudhuri, 2002).
the force is measured with strain gauges. The force is
In this study, we compared changes in pain threshold in
gradually increased at a rate of 3 N s21 until the subject
ﬁve CFS patient with ﬁve age and sex matched control
indicates that the pain level has been reached. The threshold
subjects following exercise. All CFS patients had been
is determined as the mean of the three closest values out of
previously assessed and evaluated by one of us (AC) and
ﬁve measurements. Pain thresholds were obtained before
fulﬁlled the CDC criteria for CFS (Fukuda et al., 1994). The
start of the exercise (baseline), immediately after each
selected patients were relatively less disabled and more
exercise period and a ﬁnal pain threshold 20 min after the
functional in their daily activities.
ﬁnal exercise stage.
The study was approved by the local ethics committee
Five CFS patients (median age 46 years range 28 – 49) and
(EC/02/S/57) and informed, written consent was obtained
ﬁve control subjects (median age 44 years range 30 – 54) were
studied. Each group consisted of one female and four male
* Corresponding author. Tel.: þ44-141-201-2492; fax: þ44-141-201-
volunteers. Age of the participants in both groups was
comparable, with the female volunteer being oldest in her
firstname.lastname@example.org (A. Chaudhuri).
0304-3959/$20.00 q 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
A. Whiteside et al. / Pain 109 (2004) 497–499
after a level of exertion that does not cause any tissue
damage. A reduced level of beta-endorphin in the peripheral
mononuclear cells of CFS patients has been observed
(Panerai et al., 2002) but its clinical signiﬁcance is unclear.
Sex differences in responses to experimental pain have been
widely reported, with men having higher pain tolerance than
women (Fillingim et al., 2002). Findings from both animal
and human research suggest that pain sensitivity changes
across the menstrual cycle with greater ischaemic but not
thermal pain sensitivity among females after the mid-cycle
surge of lutenising hormone (Fillingim et al., 1997).
In our experiment, male and female CFS patients did not
differ from healthy controls in terms of their pain threshold
Fig. 1. Median change in pain threshold relative to baseline following
graded exercise. Positive values indicate an increase and negative values a
at the beginning of the exercise protocol but had a
decrease in pain threshold. The error bars indicate the inter-quartile range.
progressive decline in sensory threshold to pain after
exercise. We did not observe any obvious evidence of a
respective group. All healthy volunteers and selected patients
difference in pain threshold between the sexes but the
completed the exercise protocol. None of the participants,
sample size was small and unequal ðM ¼ 4; F ¼ 1Þ for
including the CFS patients, reported any muscle pain
proper analysis. Despite the small number of subjects in the
immediately after the exercise. The median baseline pain
study, our results indicate that in comparison to the healthy
threshold was 28.6 N range 12.5 – 36.1 N for CFS subjects
controls, CFS subjects had incremental reduction in pain
and 24.9 N range 23.9 – 30.3 N for controls. The inﬂuence of
threshold after modest exercise. In normal circumstances, as
high inter-subject variability was reduced by analysing the
demonstrated by our control group, exercise increases pain
changes in pain threshold from baseline values. The pain
threshold and this is presumed to be due to the release of
threshold increased in control subjects with exercise while it
endogenous opioids and growth factors (Koltyn and
decreased in the CFS subjects as shown in Fig. 1. After the
Arbogast, 1998). Increased perception of pain and/or fatigue
third exercise period, the median increase in controls of
after exercise may be indicative of a dysfunction associated
2.7 N range 2 0.8 to 3.9 N was signiﬁcantly different from
with the central anti-nociceptive mechanism. Similar
the median decrease of 4.7 N range 1.1 – 13.3 N in CFS
observations have been made in patients with ﬁbromyalgia
subjects (P ¼ 0:0122; Mann –Whitney test). The difference
where increased perception of muscle pain is considered to
in baseline pain threshold between the single female
be due to an abnormal central nociceptive processing of the
participants in each group was not signiﬁcant. The pain
peripheral sensory input (Russell, 2002). Low serotonin
threshold for the female control did not change with exercise
(5-HT) and elevated substance P is implicated in the pain
while it was reduced in the female CFS patient.
ampliﬁcation syndrome in ﬁbromyalgia (Russell, 2002). A
similar mechanism may be responsible for pain ampliﬁca-
tion after exercise in CFS patients. Better understanding of
the central pain mechanism in CFS would be an important
step for more effective rehabilitation of the affected patients.
This is the ﬁrst study which has looked objectively at the
effect of graduated physical exercise on pain threshold in
patients with CDC deﬁned CFS. Post-exertional myalgia
and chronic muscle pain have implications for successful
rehabilitation programmes in CFS. Fatigue in CFS is
We wish to thank Lorna Paul and Rachael Crook,
primarily central (Chaudhuri and Behan, 2004) and none
Caledonian University, Glasgow for advice and use of the
of the patients in this study had exercise induced muscle
exercise facilities and Aled Evans and Donnie Smith at
fatigability or muscle cramp to suggest a peripheral origin of
DCPB, South Glasgow University Hospitals NHS Trust,
Glasgow for design and construction of the Algometer. AC
In normal physiology, a stimulus which causes or has the
is supported by the David & Frederick Barclay Foundation.
potential to cause tissue damage elicits a sensation of pain
by stimulating nociceptors. Different nociceptors are known
to have different thresholds and nociceptors with lower
thresholds may respond to pressure or heat that is not
sufﬁcient to cause tissue injury. It is considered that the low-
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- Exercise lowers pain threshold in chronic fatigue syndrome