Journal of Rehabilitation Medicine 51-10 | Page 65

Effect of exercise on neurotrophin levels in patients with FM
BDNF levels correlated with severity of insomnia (52,
53). Insomnia is common in patients with severe chro-
nic pain conditions. It was not registered in the present
study; however, assuming that fatigue is a proxy for
that, we found no relationship in a multivariate context
between fatigue aspects and BDNF levels. Reason­
ably, and in agreement with the present multivariate
analysis, the increased BDNF plasma levels in the
present group of patients with FM cannot be explained
by the presence of depressive symptoms or insomnia.
Hence, this finding supports the interpretation that
the increased levels of BDNF in FM are related to
nociception and/or pain.
Taken together, these results for NGF and BDNF
indicate alterations in the pattern of the 2 NTs, which
are involved in important processes, such as growth,
repair, and sensitization. However, with respect to the
latter, no correlations were found between BDNF and
NGF levels and PPT, which partially contradicts the
results of an earlier study reporting that a high level of
BDNF was associated with low PPT (21). It cannot be
excluded that ceiling effects may be present for pain
sensitivity (i.e. PPT) in patients with FM.
The current study found no associations between
BDNF levels and other clinical characteristics in FM.
This agrees with other FM studies, which have not
been able to establish significant correlations between
BDNF blood levels and age (17), gender (47), disease
duration (17, 47), pain intensity (17), number of tender
points (17), and disease severity according to FIQ (20).
As reported elsewhere, for the larger cohort of pa-
tients with FM we found positive clinical changes in
the resistance exercise group (Table IV) (31). Previous
studies of the same cohort have shown no, or only
significant, effects in a few cytokines (IL-1ra and IL-
1β) in plasma or in microdialysis samples from vastus
lateralis after exercise, whereas levels of metabolites
(glutamate and pyruvate) in muscle were normalized
after the 15 weeks of exercise intervention (28, 54, 55).
These findings, together with the present finding con-
cerning NGF and BDNF, may suggest that the exercise
programme affects the metabolic profile in muscle, but
does not affect the immune profile in plasma in FM.
Hence, the FM group shows a chronic inflammatory
profile that is not normalized after 15 weeks of resis-
tance exercise. Future studies analysing other specific
proteins involved in muscle strength are warranted.
Strengths and limitations
One of the greatest strengths of this study is its design.
Multi-centre study design provides relatively large
study population, which would otherwise be difficult
to achieve. The limitation of this study is the lack of
785
recovery time after the interventions, which is possibly
needed to normalize the plasma levels of NGF and
BDNF. Post-interventional blood samples were taken
one week after therapy programmes ended and there
were no follow-up re-examinations. Some previous
neuropeptide studies have reached a post-therapy
reduction in neuropeptides when the follow-up time
was several months (56).
Conclusion
This study found alterations in 2 molecules involved in
sensitization and plasticity and recovery of the nervous
system. This study, the first to investigate circulating
NGF in FM, found significantly lowered levels of
circulating NGF. These results do not indicate a role
of anti-NGF treatment in FM. Plasma levels of NGF
were significantly lower in patients with FM, whereas
levels of BDNF were significantly higher in patients
with FM. Progressive resistance exercise therapy or
relaxation therapy for FM had no effect on the levels
of these substances. No correlations existed between
the 2 NTs and clinical characteristics, including pain
sensitivity and intervention outcomes. The present
study indicates that peripheral factors (i.e. alterations
in NGF and BDNF) may be important for nociception
and pain in patients with FM.
ACKNOWLEDGEMENT
The study was supported by the Swedish Rheumatism As-
sociation, the Health and Medical Care Executive Board of
Västra Götaland Region, ALF-LUA at Sahlgrenska University
Hospital, Stockholm County Council (ALF), and ALF grants at
Region Östergötland. Linköping University Hospital Research
Fund. Swedish Research Council (K2013-52X-22199-01-3,
K2015-99x-21874-05-4, 521-2010–2893), Karolinska Institute
Foundation and AFA Insurance (140341) and NEURO Sweden.
The funders had no role in the study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
The authors have no conflicts of interest to declare.
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