Journal of Rehabilitation Medicine 51-10 | Page 61
Effect of exercise on neurotrophin levels in patients with FM
interest in participating in the study. After telephone screening,
177 women took part in a medical examination, of whom 130
fulfilled the inclusion criteria and were included in the study.
Age, weight, height, and blood pressure were registered, and
body mass index (BMI) was recorded. Subjects answered a
range of questionnaires about their pain and general and psy-
chological health. Functional tests and tender-point thresholds
testing were performed. A 20-ml blood sample was collected.
Finally, the women with FM were randomized into 2 groups:
those who received resistance exercise and those who received
relaxation therapy (34). A 20-ml blood sample was also collected
after the intervention.
The control group (healthy controls; HC) included 130 heal-
thy, age-matched, and pain-free women. The control group
underwent the same procedures and similar data were collected
for baseline comparison (34).
Subjects
As described above, there were originally 260 participants in the
multi-centre study: 130 women with FM and 130 HC. Plasma
levels of cytokines and chemokines for the total cohort were
previously analysed (28). Plasma samples from 100 participants
were available for analysis of NGF and BDNF and consequently
only those subjects were included in this study; 75 out of the
100 were women with FM and 25 were HC.
After receiving verbal and written information about the study,
all subjects signed a consent form, which was in accordance
with the Declaration of Helsinki. The study was approved by
the Regional Ethics Committee in Stockholm (Dnr: 2010/1121-
31/3) and was registered on 21 October 2010 (Clinicaltrials.
gov NCT01226784).
Variables registered
Age, BMI, and systolic and diastolic blood pressures were
registered at baseline, as well as FM duration and number of
tender points. Psychometric variables and PPT were registered
at baseline (both FM and HC) and after the interventions (only
in FM). Data have previously been presented for the total co-
hort (FM: n = 130 and HC: n = 125) (28, 31). Details about the
variables are presented in those studies (28, 31). Global pain
intensity was measured using a 0–100-mm visual analogue
scale (VAS), where 0=no pain and 100=worst pain imaginable.
The Hospital Anxiety and Depression Scale (HADS) and Pain
Catastrophizing Scale (PCS) were used to detect psychological
distress of study participants. Two summary components from
the Short-Form Health Survey (SF36), physical (SF36-PSC)
and mental (SF36-MSC), were used to define quality of life;
a high score indicates better health. The Fibromyalgia Impact
Questionnaire (FIQ) was used to portray the grade of symptoms
and disabilities. The Multidimensional Fatigue Inventory (MFI)
was used to evaluate different dimensions of fatigue. A higher
score on FIQ and MFI indicates lower health (28, 31). PPTs
were measured with an electronic pressure algometer (Somedic,
Hörby, Sweden) over 4 bilateral points, as recently described
in detail (28, 31).
Resistance exercise therapy and relaxation therapy
The women with FM were randomized to 2 intervention groups:
resistance exercise or relaxation therapy (as reported earlier)
(31). In this sub-study, 41 out of 75 subjects (54.7%) were ran-
domized to the resistance exercise group and 34 subjects were
781
randomized to the relaxation therapy group. All the healthy
controls underwent the resistance exercise intervention, but
data from them were not collected afterwards.
Both interventions lasted 15 weeks and have been described in
detail elsewhere (31). The programme of progressive resistance
exercise included training twice per week and was supervised by
physical therapists. All sessions started with a 10-min warm-up
and continued with 50 min of strength training focussing on the
lower body. The training programme started with 40% of the
maximum voluntary capacity (MVC) and continuously deve-
loped up to 70–80% of MVC during the 15-week period (31).
The relaxation therapy was selected as an active control
intervention. It was provided twice a week as a 25-min session
under the supervision of physiotherapists. The intervention
contained mental exercises, e.g. relaxation and autosuggestion.
The patients were guided through all the body parts, where
each part was in focus one at a time. All sessions ended with
stretching (31).
Blood samples
At baseline and after the 15-week intervention, 20 ml of blood
were collected from all study participants. The blood was taken
from the decubital vein. Samples were directly placed on ice
and transported to the local laboratories. Blood was centrifuged
and plasma was separated, aliquoted, and stored at –86°C until
analysis (28).
Biochemical analysis
Plasma samples were analysed for NGF and BDNF using the
customized multiplex electrochemiluminescence assay panel
from Meso Scale Discovery (MSD, Rockville, MD, USA) ac-
cording to the manufacturer’s protocol. The limits of detection
(LOD) were 0.33 pg/ml for NFG and 5.09 pg/ml for BDNF.
Levels of cytokines and chemokines (IFN-ɣ, IL-1β, IL-2,
IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IL-1ra, eotaxin, IP-10,
and MCP-1) have been reported for the total cohort (i.e. FM:
n = 125 and HC: n = 130) (28). From these analyses, we have
used results from 75 women with FM and 25 healthy controls,
which were included in this study. Analyses were performed
using Luminex technology (Bio-Plex, Bio-Rad Laboratories
Inc., Hercules, CA, USA) standard kits.
Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics
(version 24.0: IBM Corporation, Somers, NY, USA) for tradi-
tional statistical analyses, and SIMCA v.14.0 (UMETRICS,
Umeå, Sweden) was used for advanced multivariate analysis
(MVDA). Mann–Whitney U test was used for comparisons bet-
ween FM and HC. The Wilcoxon signed-rank test was used for
comparisons within groups (i.e. before vs after the intervention).
Significance of the statistical tests was set at p < 0.05. Unless
stated otherwise, data are expressed as mean (standard deviation;
SD). Survey data regarding FM duration, tender points, VAS
global pain, PPT, and PCS were missing from 3 subjects in the
FM group. Survey data regarding PPT, SF36, and MFI were
missing from one healthy control. These subjects were excluded
from the calculation regarding these variables.
To investigate the multivariate correlations between the
neuropeptides, cytokines/chemokines, clinical outcomes, and
group belonging orthogonal partial least squares discriminant
analysis (OPLS-DA) were applied. First, data were overviewed
J Rehabil Med 51, 2019