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Table 3 Characteristics of included trials related to neuropeptides

From: Effects of non-pharmacological interventions on inflammatory biomarker expression in patients with fibromyalgia: a systematic review

Reference Participants Study design Diagnosis of FM Treatment group Control group Study duration Outcomes Findings
Bojner-Horwitz et al. (2003) [36] N = 36 RCT ACR 1990 Dance/movement Waiting control 14 months PRL, NPY, DHEA-S, cortisol The levels of serum PRL in both groups increased across the study interval, with the largest increase in the intervention group
Mean age: (n = 20) (n = 16)   4 time points (at baseline, and at months 4, 6, and
14 of the study)
57 ± 7.2 years (total) 6 months 6 months   There were no significant differences between baseline and 14 months in the levels of serum PRL between the two groups
Gender: once a week   
female only 1 h each serum, saliva The levels of serum NPY in both groups increased from baseline to month 4, decreased from months 4 − 6, and increased from months 6 − 14
There were no significant differences in the levels of serum NPY between the two groups across the study interval
Lund et al. (2006) [32] N = 19 RCT ACR 1990 Massage Guided relaxation 10 weeks CRF-LI In the massage group, the concentrations of urinary CRF-LI decreased after 6 weeks of massage treatment (p = 0.01) and 1 month after completion of treatments (p <0.5)
Mean age: (n = 10) (n = 9) 3 time points (prior to treatment, after 6-week treatment and 1 month after completed treatment) urine
50.7 ± 9.7 years (total) 6 weeks 6 weeks
Gender: twice weekly twice weekly
f+emale only 30 minutes each (feet and legs 18 minutes, hands and arm 8 minutes, face 4 minutes) 30 minutes each
Bjersing et al. (2012) [26] N = 49 RCT ACR 1990 Nordic walking Active control: low-intensity walking 30 weeks SP, NPY, The change in the levels of serum IGF-1 correlated positively with alterations in CSF SP (p <0.1), NPY (p <0.01) and pain threshold (p <0.1)
Mean age: (N = 26) (n = 23) IL-6, IL-8, IGF-1, IGFBP3, NGF, MMP-3
52 years (total) 15 weeks 15 weeks 3 time points
Gender: twice a week twice a week (baseline, after 15 weeks of exercise, 30 weeks of follow up)
female only 40–45 minutes each 40–45 minutes each
serum, CSF
Bazzichi et al. (2013) [33] N = 41 RCT ACR 1990 Balneotherapy Active control: mud-bath therapy 12 weeks BDNF, oxytocin, The concentrations of serum BDNF significantly decreased in both balneo-therapy and mud-bath therapy after 12 weeks (p < 0.05, p < 0.01, respectively), while there was no significant change in the levels of oxytocin.
Mean age: (n = 20) (n = 21) SERT binding parameters, ATP
54.0 ± 7.2 years (balneotherapy) 2 weeks 2 weeks 3 time points
52.8 ± 10.2 years (mud-bath therapy) 6 days a week 6 days a week (at baseline, after 2 weeks and after 12 weeks)
Gender: 20 minutes each 20 minutes each (mud pack 10 minutes and immersion in thermal water 10 minutes)  
19/1 female/male (balneotherapy)   plasma, serum, salivary adiponectin, leptin, resistin, NPY, IGF-1, IGFBP3, NGF
20/1 female/male (mud-bath therapy)  
Bjersing et al. (2013) [27] N = 48 RCT ACR 1990 Nordic walking Active control: low-intensity walking 30 weeks   The levels of serum resistin increased in the group as a whole after 30 weeks (p <0.05) which correlated with decreased fatigue
Mean age: (n = 26) (n = 22)
52.0 years (lean group) (lean 4, overweight 15, obese 7) (lean 5, overweight 11, obese 6) 3 time points The levels of serum NPY increased in the group as a whole after 30 weeks (p <0.05). This increase was only significant in obese patients (p <0.05)
(BMI 18.5 to 24.9, n = 9) 15 weeks 15 weeks (baseline, after 15 weeks of exercise, 30 weeks of follow up) serum, CSF
53.0 years (overweight group) twice a week twice a week
(BMI 25 to 29.9, n = 26) 40–45 minutes each 40–45 minutes each
51.0 years (obese group)   
(BMI ≥30, n = 13)   
Gender:   
female only   
  1. ACR American College of Rheumatology, ATP adenosine 5′-triphosphate, BDNF brain-derived neurotrophic factor, BMI body mass index, CRF-L1 corticotropin releasing factor-like immunoreactivity, CSF cerebrospinal fluid, DHEA-S dehydroepiandrosterone sulfate, IGFBP-3 insulin-like growth factor-binding protein-3, IGF-1, insulin-like growth factor-1, IL interleukin, MMP-3 matrix metallopeptidase-3, NGF nerve growth factor, Non-RCT non-randomized controlled trial, NPY neuropeptide Y, PRL prolactin, RCT randomized controlled trial, SERT serotonin transporter, SP surfactant protein