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. 2019 Nov 22;10:1382. doi: 10.3389/fphar.2019.01382

Table 3.

MANCOVA model to compare the treatment effect in the Δ-value of psychophysical pain measures and the neuroplasticity state considering melatonin’s effect, depressive symptoms and sleep quality (n = 36).

(A) Main effects
Corrected model Type III sum of squares df Mean square F P-value η² partial
Dependent variables
Δ- Changes on NPS0–10 during CPM-task 102.47a 4 25.62 10.99 <0.01 0.60
Δ- Heat pain threshold 285.03b 4 71.26 13.18 <0.01 0.65
Δ-Heat pain tolerance 79.17c 4 19.79 5.56 <0.01 0.43
Δ-Brain-derived neurotrophic factor (BDNF) 5,176.77d 4 1,294.19 7.89 <0.01 0.52
Δ- Tropomyosin receptor kinase B (TrkB) 0.62e 4 0.16 6.13 <0.01 0.46
Δ- S100 calcium binding protein B (S-100B) 1,871.64f 4 467.91 3.88 0.01 0.35
Intercept
Δ- Changes on NPS0–10 during CPM-task 4.40 1 4.40 1.89 0.18 0.06
Δ- Heat pain threshold 1.18 1 1.18 0.22 0.65 0.01
Δ-Heat pain tolerance 1.47 1 1.47 0.41 0.53 0.01
Δ-Brain-derived neurotrophic factor (BDNF) 2,133.52 1 2,133.52 13.01 <0.01 0.31
Δ- Tropomyosin receptor kinase B (TrkB) 0.16 1 0.16 6.37 0.02 0.18
Δ- S100 calcium binding protein B (S-100B) 405.62 1 405.61 3.36 0.08 0.10
Treatment group
Δ- Changes on NPS0–10 during CPM-task 59.85 1 59.85 25.69 <0.01 0.47
Δ- Heat pain threshold 154.14 1 154.14 28.50 <0.01 0.49
Δ-Heat pain tolerance 60.56 1 60.56 17.01 <0.01 0.37
Δ-Brain-derived neurotrophic factor (BDNF) 2,375.01 1 2,375.01 14.48 <0.01 0.33
Δ- Tropomyosin receptor kinase B (TrkB) 0.45 1 0.46 18.01 <0.01 0.38
Δ- S100 calcium binding protein B (S-100B) 703.52 1 703.52 5.83 0.02 0.17
Δ-Pittsburgh Sleep Quality Index
Δ- Changes on NPS0–10 during CPM-task 9.95 1 9.95 4.27 0.048 0.13
Δ- Heat pain threshold 24.57 1 24.57 4.54 0.042 0.14
Δ-Heat pain tolerance 14.37 1 14.37 4.04 0.054 0.12
Δ-Brain-derived neurotrophic factor (BDNF) 208.11 1 208.11 1.27 0.269 0.04
Δ- Tropomyosin receptor kinase B (TrkB) 0.11 1 0.11 4.32 0.047 0.13
Δ- S100 calcium binding protein B (S-100B) 8.18 1 8.175 0.08 0.796 <0.01
Δ-Beck Depression Inventory-II
Δ- Changes on NPS0–10 during 0.32 1 0.32 0.14 0.71 <0.01
Δ- Heat pain threshold 0.03 1 0.03 0.01 0.94 <0.01
Δ-Heat pain tolerance 4.79 1 4.79 1.35 0.26 0.04
Δ-Brain-derived neurotrophic factor (BDNF) 2.47 1 2.47 0.06 0.90 <0.01
Δ- Tropomyosin receptor kinase B (TrkB) 0.04 1 0.04 1.59 0.22 0.05
Δ- S100 calcium binding protein B (S-100B) 14.71 1 14.71 0.12 0.73 <0.01
Grupo * Δ-Pittsburgh Sleep Quality Index
Δ- Changes on NPS0–10 during CPM-task 1.42 1 1.41 0.61 0.44 0.02
Δ- Heat pain threshold 0.13 1 0.11 0.02 0.89 <0.01
Δ-Heat pain tolerance 3.86 1 3.86 1.09 0.31 0.04
Δ-Brain-derived neurotrophic factor (BDNF) 419.34 1 419.34 2.56 0.12 0.08
Δ- Tropomyosin receptor kinase B (TrkB) 0.08 1 0.08 3.00 0.09 0.09
Δ- S100 calcium binding protein B (S-100B) 71.13 1 71.13 0.59 0.45 0.02
(B) Coefficients
Beta SEM t P-value CI 95%
Dependent variable: Δ-changes on NPS (0–10) during the CPM-task
Treatment group Melatonin −4.97 0.98 −5.07 0.00* (−6.98 to −2.97)
Placebo 0reference
Δ-Pittsburgh Sleep Quality Index −0.37 0.17 −2.20 0.03* (−0.70 to −0.03)
Δ-Beck Depression Inventory-II −0.02 0.05 −0.37 0.71 (−0.12 to 0.09)
Interaction
Melatonin* Δ-Pittsburgh Sleep Quality Index 0.20 0.27 0.78 0.44 (−0.33 to 0.75)
Placebo* Δ-Pittsburgh Sleep Quality Index 0reference
Dependent variable: Δ-heat pain threshold
Treatment group Melatonin 7.981 1.49 5.34 0.00* (4.92 to 11.03)
Placebo 0reference
Δ-Pittsburgh Sleep Quality Index 0.44 0.25 1.75 0.09 (−0.07 to 0.96)
Δ-Beck Depression Inventory-II −0.006 0.08 −0.08 0.94 (−0.16 to 0.15)
Interaction
Melatonin* Δ-Pittsburgh Sleep Quality Index −0.06 0.40 −0.14 0.88 (−0.88 to 0.77)
Placebo* Δ-Pittsburgh Sleep Quality Index 0reference
Dependent variable: Δ-heat pain tolerance
Treatment group Melatonin 5.00 1.21 4.12 0.00* (2.52 to 7.48)
Placebo 0reference
Δ-Pittsburgh Sleep Quality Index 0.49 0.20 2.38 0.02* (0.06 to 0.90)
Δ-Beck Depression Inventory-II 0.07 0.06 1.16 0.25 (−0.006 to 0.20)
Interaction
Melatonin* Δ-Pittsburgh Sleep Quality Index −0.34 0.33 −1.04 0.30 (−1.0 to 0.32)
Placebo * Δ-Pittsburgh Sleep Quality Index 0reference
Dependent variable: Δ-Brain-derived neurotrophic factor (BDNF)
Treatment group Melatonin −31.33 8.23 −3.80 0.00* (−48.16 to −14.49)
Placebo 0reference
Δ-Pittsburgh Sleep Quality Index 0.58 1.39 0.42 0.68 (−2.26 to 3.41)
Δ-Beck Depression Inventory-II −0.05 0.42 −0.12 0.90 (−0.93 to 0.82)
Interaction
Melatonin* Δ-Pittsburgh Sleep Quality Index −3.55 2.22 −1.56 0.12 (−8.09 to 0.90)
Placebo* Δ-Pittsburgh Sleep Quality Index 0reference
Dependent variable: Δ- Tropomyosin receptor kinase B (TrkB)
Treatment group Melatonin −0.43 0.102 −4.24 0.00* (−0.64 to −0.23)
Placebo 0reference
Δ-Pittsburgh Sleep Quality Index −0.004 0.017 0.20 0.84 (−0.04 to 0.03)
Δ-Beck Depression Inventory-II −0.007 0.005 −1.26 0.21 (−0.02 to 0.004)
Interaction
Melatonin* Δ-Pittsburgh Sleep Quality Index −0.05 0.03 −1.73 0.09 (−0.10 to 0.009)
Placebo* Δ-Pittsburgh Sleep Quality Index 0reference
Dependent variable: Δ- S100 calcium binding protein B (S-100B)
Treatment group Melatonin −17.05 7.06 −2.41 0.02* (−31.49 to −2.61)
Placebo 0reference
Δ-Pittsburgh Sleep Quality Index 0.49 1.18 0.41 0.68 (−1.94 to 2.92)
Δ-Beck Depression Inventory-II −0.13 0.36 −0.35 0.73 (−0.88 to 0.62)
Interaction
Melatonin* Δ-Pittsburgh Sleep Quality Index −1.46 1.90 −0.77 0.45 (−5.35 to 2.43)
Placebo* Δ-Pittsburgh Sleep Quality Index 0reference

R2 = 0.603 (adjusted R2 = 0.548)a

R2 = 0.645 (adjusted R2 = 0.596)b

R2 = 0.434 (adjusted R2 = 0.356)c

R2 = 0.521 (adjusted R2 = 0.455)d

R2 = 0.458 (adjusted R2 = 0.384)e

R2 = 0.349 (adjusted R2 = 0.259)f