| Number of original studies (N) | Total number of comparisons (N) | Pooled SMD (if applicable) | Favors |
---|---|---|---|---|
Neuroinflammation markers | ||||
Brainstem | Â | Â | Â | Â |
 1.1.1 Microglia (Iba1) | 1 | 1 | N.A. (see Additional file 3 C1) |  |
Dorsal horn | Â | Â | Â | Â |
 1.2.1 Microglia (Iba1 or CD−11b+) | 6 | 13 | − 1.34 [− 1.99, − 0.68] | EXP |
 1.2.2 BDNF + Iba1 | 1 | 3 | N.A. (see Additional file 3 C1) |  |
 1.2.3 Astrocytes (GFAP) | 3 | 7 | − 1.40 [− 2.39, − 0.41] | EXP |
 1.2.4 HDAC + nuclei | 1 | 1 | N.A. (see Additional file 3 C1) |  |
Ventral horn (Motoneurons) | Â | Â | Â | Â |
 1.3.1 Microgliaa (Iba1) | 2 | 6 | − 1.62 [− 3.70, 0.45] | NS |
 1.3.2 Astrocytesa (GFAP) | 2 | 6 | 7.50 [3.33, 11.68] | EXP |
Dorsal root ganglion | Â | Â | Â | Â |
 1.4.1 Astrocytes | 1 | 1 | N.A. (see Additional file 3 C1) |  |
Macrophages | Â | Â | Â | Â |
Spinal cord (unspecified) | Â | Â | Â | Â |
 2.1.1 Macrophage density | 1 | 3 | N.A. (see Additional file 3 C2) |  |
Nerve | Â | Â | Â | Â |
 2.2.1 Number of macrophages (F4/80) | 2 | 2 | − 0.38 [− 1.85, 1.09] | NS |
 2.2.2 Number of CD68 + macrophages | 1 | 1 | N.A. (see Additional file 3 C2) |  |
 2.2.3 Number of CD206 + macrophages | 1 | 1 | N.A. (see Additional file 3 C2) |  |
 2.2.4. Relative proportion M1 Macrophagesb (% of total macrophages) | 1 | 1 | N.A. (see Additional file 3 C2) |  |
 2.2.5. Relative proportion M2 Macrophagesb (% of total macrophages) | 1 | 1 | N.A. (see Additional file 3 C2) |  |
 2.2.6. Relative proportion Intermediate Macrophagesb (% of total macrophages) | 1 | 0 | N.A |  |
Neurotrophins | Â | Â | Â | Â |
Brain | Â | Â | Â | Â |
 A) Cerebral cortex  3.1.1 BDNF | 1 | 2 | N.A. (see Additional file 3 C3) |  |
 B) Brainstem  3.2.1 BDNF | 2 | 3 | 0.49 [− 0.13, 1.11] | NS |
Spinal cord (unspecified) | Â | Â | Â | Â |
 3.3.1 BDNF | 2 | 3 | − 0.99 [− 1.69, − 0.29] | EXP |
 3.3.4 β-NGF | 1 | 1 | N.A. (see Additional file 3 C3) |  |
Dorsal horn | Â | Â | Â | Â |
 3.4.1 BDNF | 1 | 5 | N.A. (see Additional file 3 C3) |  |
 3.4.3 NT3 | 1 | 1 | N.A. (see Additional file 3 C3) |  |
Ventral horn | Â | Â | Â | Â |
 3.5.1 BDNF mRNA | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.5.2 NT3 mRNA | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.5.3 NGF mRNA | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.5.4 GDNF mRNA | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.5.5 TrkB receptor | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.5.6 TrkC receptor | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.5.7 p-AKT/AKT | 1 | 1 | N.A. (see Additional file 3 C3) |  |
Dorsal root ganglion | Â | Â | Â | Â |
 3.6.1 BDNF / BDNF mRNA | 2 | 2 | − 1.01 [− 1.70, − 0.31] | EXP |
 3.6.2 NGF / NGF mRNA | 3 | 4 | − 0.64 [− 1.29, 0.00] | EXP |
 3.6.3 GDNF / GDNF mRNA | 2 | 2 | − 1.30 [− 3.30, 0.69] | NS |
 3.6.4 NT3 mRNA | 1 | 1 | N.A. (see Additional file 3 C3) |  |
Nerve | Â | Â | Â | Â |
 3.7.1 BDNF / BDNF mRNA | 3 | 3 | 0.21 [− 1.38, 1.81] | NS |
 3.7.2 GDNF | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.7.3 IGF-1 | 2 | 2 | 1.72 [0.87, 2.57] | EXP |
Blood/serum | Â | Â | Â | Â |
 3.8.1 BDNFc | 1 | 0 | N.A |  |
 3.8.2 GDNF | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.8.3 IGF-1 | 2 | 2 | 3.35 [− 2.59, 9.28] | NS |
Muscle | Â | Â | Â | Â |
 3.9.1 BDNF | 2 | 3 | 3.12 [2.00, 4.24] | EXP |
 3.9.2 GDNF | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.9.3 IGF-1 / IGF-1 mRNAd | 3 | 3 | 0.97 [− 1.27, 3.22] | NS |
 3.9.4 TrkB kinase | 1 | 1 | N.A. (see Additional file 3 C3) |  |
 3.9.5 p-TrkB receptors | 1 | 1 | N.A. (see Additional file 3 C3) |  |
Liver | Â | Â | Â | Â |
 3.10.1 IGF-1 mRNA | 1 | 1 | N.A. (see Additional file 3 C3) |  |
Cytokines | Â | Â | Â | Â |
Cerebral cortex | Â | Â | Â | Â |
 4.1.1 IL-1β | 1 | 2 | N.A. (see Additional file 3 C4) |  |
 4.1.2 IL-4 | 1 | 2 | N.A. (see Additional file 3 C4) |  |
Brainstem | Â | Â | Â | Â |
 4.2.1 TNF-α | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.2.2 IL-1β | 2 | 3 | 0.24 [− 1.43, 1.91] | NS |
 4.2.3 IL-4 | 1 | 2 | N.A. (see Additional file 3 C4) |  |
Spinal cord (unspecified) | Â | Â | Â | Â |
 4.3.1 TNF-α | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.3.2 IL-1β | 2 | 3 | − 0.54 [− 1.18, 0.10] | NS |
 4.3.4 IL-4 | 1 | 2 | N.A. (see Additional file 3 C4) |  |
 4.3.6 IL-6 | 1 | 2 | N.A. (see Additional file 3 C4) |  |
 4.3.7 IL-6 receptor | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.3.8 IL-10 | 2 | 3 | 0.60 [− 0.39, 1.60] | NS |
 4.3.9 Irisin | 1 | 1 | N.A. (see Additional file 3 C4) |  |
Dorsal horn | Â | Â | Â | Â |
 4.4.1 IL-1 receptor antagonist | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.4.2 IL-4 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.4.3 IL-5 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.4.4 IL-6 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
Nerve | Â | Â | Â | Â |
 4.5.1 TNF-α | 5 | 10 | -1.10 [− 1.81, − 0.39] | EXP |
 4.5.2 IL-1β | 3 | 4 | − 0.89 [− 1.98, 0.21] | NS |
 4.5.3 IL-1 receptor antagonist | 2 | 2 | 0.64 [− 0.70, 1.99] | NS |
4.5.4 IL-4 | 2 | 2 | 0.54 [− 0.62, 1.69] | NS |
 4.5.5 IL-5 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.5.6 IL-6 | 4 | 8 | − 0.42 [− 1.78, 0.93] | NS |
 4.5.7 IL-6 receptor | 2 | 2 | 1.36 [− 3.16, 5.88] | NS |
 4.5.8 STAT3 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.5.9 IL-10 | 3 | 7 | 0.40 [− 0.54, 1.35] | NS |
Blood/serum | Â | Â | Â | Â |
 4.6.1 IL-6 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
Muscle | Â | Â | Â | Â |
 4.7.1 TNF-α | 2 | 2 | − 1.06 [− 2.12, − 0.01] | EXP |
 4.7.2 IL-1β | 2 | 2 | − 0.57 [− 1.52, 0.39] | NS |
 4.7.3 IL-1ra | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.7.4 IL-4 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
 4.7.5 IL-6 | 1 | 1 | N.A. (see Additional file 3 C4) |  |
Cerebrospinal fluid | Â | Â | Â | Â |
 4.8.1 TNF-α | 1 | 1 | N.A. (see Additional file 3 C4) |  |
Neurotransmitters | Â | Â | Â | Â |
(nor)adrenergic | Â | Â | Â | Â |
 Brainstem |  |  |  |  |
  5.1.1 α1a receptor | 1 | 1 | N.A. (see Additional file 3 C5) |  |
  5.1.2 β2 receptor | 1 | 1 | N.A. (see Additional file 3 C5) |  |
 Dorsal horn |  |  |  |  |
  5.2.1 α1a receptor | 1 | 1 | N.A. (see Additional file 3 C5) |  |
  5.2.2 β2 receptor | 1 | 1 | N.A. (see Additional file 3 C5) |  |
Serotonin | Â | Â | Â | Â |
 Brainstem |  |  |  |  |
  6.1.1 5-HT (unspecified)e | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.2 5-HT 1A receptor | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.3 5-HT 1B receptor | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.4 5-HT 2A receptor/receptor mRNA | 2 | 2 | 1.25 [0.49, 2.01] | EXP |
  6.1.5 5-HT 2C receptor | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.6 5-HT 3A receptor | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.7 5-HT 7 receptor | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.8 SERT (serotonin transporter) | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.1.9 Tryptophan hydroxylase 2 (Tph2) | 1 | 1 | N.A. (see Additional file 3 C6) |  |
 Dorsal horn |  |  |  |  |
  6.2.1 5-HT receptor (unspecified) | 1 | 1 | N.A. (see Additional file 3 C6) |  |
  6.2.2 5-HT 2A receptor | 1 | 1 | N.A. (see Additional file 3 C6) |  |
 Ventral horn |  |  |  |  |
  6.3.1 5-HT receptor (unspecified) | 1 | 1 | N.A. (see Additional file 3 C6) |  |
GABA | Â | Â | Â | Â |
 SPINAL CORD (unspecified) |  |  |  |  |
  7.1.1 GAD65 | 1 | 1 | N.A. (see Additional file 3 C7) |  |
 Dorsal horn |  |  |  |  |
  7.2.1 GABA | 1 | 1 | N.A. (see Additional file 3 C7) |  |
  7.2.2 GABA + /NeuN + neurons | 1 | 1 | N.A. (see Additional file 3 C7) |  |
  7.2.4 GAD65/67 (no distinction) | 1 | 1 | N.A. (see Additional file 3 C7) |  |
  7.2.6 Rnf34 | 1 | 3 | N.A. (see Additional file 3 C7) |  |
 Ventral horn |  |  |  |  |
  7.1.5 GAD67 | 2 | 5 | 0.88 [-0.38, 2.13] | NS |
Dopamine | Â | Â | Â | Â |
 Brainstem |  |  |  |  |
  8.1.1 TH immunoreactivity | 1 | 1 | N.A. (see Additional file 3 C8) |  |
Purine | Â | Â | Â | Â |
 Spinal cord (unspecified) |  |  |  |  |
  9.1.1 P2X3 (ATP receptor) | 1 | 1 | N.A. (see Additional file 3 C9) |  |
Opioid system | Â | Â | Â | Â |
 Brainstem |  |  |  |  |
  10.1.1 μ-opioid receptor | 1 | 1 | N.A. (SEE Additional file 3 C10) |  |
  10.1.2 β-endorphin | 1 | 5 | N.A. (see Additional file 3 C10) |  |
 Spinal cord (unspecified) |  |  |  |  |
  10.2.1 μ-opioid receptor | 1 | 1 | N.A. (see Additional file 3 C10) |  |
 Dorsal horn |  |  |  |  |
  10.3.1 μ-opioid receptor | 1 | 5 | N.A. (see Additional file 3 C10) |  |
Neuropeptides | Â | Â | Â | Â |
Dorsal horn | Â | Â | Â | Â |
 11.1.1 CGRP | 1 | 3 | N.A. (see Additional file 3 C11) |  |
 11.1.2 PACAP mRNA | 1 | 3 | N.A. (see Additional file 3 C11) |  |
Bone | Â | Â | Â | Â |
 11.4.1 Substance P | 1 | 1 | N.A. (see Additional file 3 C11) |  |
(Sub)epidermis | Â | Â | Â | Â |
 11.5.1 Intraepidermal nerve fiber density | 1 | 2 | N.A. (see Additional file 3 C11) |  |
 11.5.2 CGRP | 1 | 3 | N.A. (see Additional file 3 C11) |  |
 11.5.4 PGP | 1 | 3 | N.A. (see Additional file 3 C11) |  |
Synaptic stripping | Â | Â | Â | Â |
Dorsal horn | Â | Â | Â | Â |
 12.1.1 Synaptophysin | 1 | 1 | N.A. (see Additional file 3 C12) |  |
Ventral horn (motoneurons) | Â | Â | Â | Â |
 12.2.1 Synaptophysine,f | 3 | 10 | 2.05 [1.32, 2.77] | EXP |
 12.2.2 Vglut1e,f | 5 | 15 | 1.38 [0.62, 2.15] | EXP |
 12.2.3 Gephyrin | 1 | 4 | N.A. (see Additional file 3 C12) |  |
 12.2.4 Perineuronal Netse | 3 | 10 | 0.39 [− 0.31, 1.09] | NS |
 12.2.5 VGat1e | 2 | 6 | − 2.99 [− 4.72, − 1.26] | EXP |
 C-Boutons | 1 | 5 | N.A. (see Additional file 3 C12) |  |
Other | Â | Â | Â | Â |
Potassium-chloride cotransporters (KCC) | Â | Â | Â | Â |
 Dorsal horn |  |  |  |  |
  13.1.1 KCC2e | 1 | 2 | N.A. (see Additional file 3 C13) |  |
  13.1.2 pKCC2 | 1 | 2 | N.A. (see Additional file 3 C13) |  |
 Dorsal root ganglion |  |  |  |  |
  13.2.1 NKCC1 | 1 | 2 | N.A. (see Additional file 3 C13) |  |
  13.2.2 pNKCC1 | 1 | 2 | N.A. (see Additional file 3 C13) |  |
MAPK signaling pathway | Â | Â | Â | Â |
 Nerve |  |  |  |  |
  14.1.1 p-ERK1/2 | 1 | 2 | N.A. (see Additional file 3 C14) |  |
  14.1.2 p-38MAPK | 1 | 2 | N.A. (see Additional file 3 C14) |  |
  14.1.3 c-Jun N-terminated kinase (JNK) | 1 | 2 | N.A. (see Additional file 3 C14) |  |
  14.1.4 p–c-Jun | 1 | 2 | N.A. (see Additional file 3 C14) |  |
  14.1.5 ATF3 | 1 | 2 | N.A. (see Additional file 3 C14) |  |
GAP43 | Â | Â | Â | Â |
 Dorsal root ganglion |  |  |  |  |
  15.1.1 CGRP + GAP43 | 1 | 1 | N.A. (see Additional file 3 C15) |  |
 Nerve |  |  |  |  |
  15.2.1 GAP43 | 2 | 3 | 0.76 [0.17, 1.35] | EXP |
 (Sub)epidermis |  |  |  |  |
  15.3.1 CGRP + GAP43g | 1 | 3 | N.A. (see Additional file 3 C15) |  |
CREB | Â | Â | Â | Â |
 Brainstem |  |  |  |  |
  16.1.1 p-CREB | 1 | 1 | N.A. (see Additional file 3 C16) |  |
  15.1.2 p-CREB/TH +  | 1 | 1 | N.A. (see Additional file 3 C16) |  |
 Dorsal horn |  |  |  |  |
  16.2.1 p-CREB | 1 | 1 | N.A. (see Additional file 3 C16) |  |
  16.2.2 total CREB | 1 | 1 | N.A. (see Additional file 3 C16) |  |
 Nerve |  |  |  |  |
  16.3.1 p-CREB | 1 | 2 | N.A. (see Additional file 3 C16) |  |
Oxidative stress | Â | Â | Â | Â |
 Serum |  |  |  |  |
  17.2.1 FRAP | 1 | 1 | N.A. (see Additional file 3 C17) |  |
  17.2.2 MDA | 1 | 1 | N.A. (see Additional file 3 C17) |  |
PLCy-1 | Â | Â | Â | Â |
 Dorsal horn |  |  |  |  |
  18.1.1 phosphorylated PLCy-1 | 1 | 1 | N.A. (see Additional file 3 C18) |  |
  18.1.2 total PLCy-1 | 1 | 1 | N.A. (see Additional file 3 C18) |  |
Heat shock protein 72 | Â | Â | Â | Â |
 Nerve |  |  |  |  |
  Heat shock protein 72h | 1 | 0 | N.A |  |