The pathophysiological mechanism of CPSP caused by thalamus haemorrhage in rodents and non-human primates
| Animals | Model of CPSP | Behavioural testing | Mechanism and lesion site | Experimental design | Ref |
| SD rats | Right VPL Collagenase (Coll) IV (0.025U) | PWMT (FBP, 7–28 days, n=8) OFT, novelty-suppressed feeding test, elevated plus maze test, FST | HIF-1α/NLRP3↑ | Blind (B), Randomisation (R) | 2 |
| PWMT (FBP, 28 days, n=14) | Endoplasmic reticulum stress/ inflammation interactions/ central sensitisation | B, R | 42 | ||
| PWMT (FBP, 28 days, n=10), PWTL (no changes) | 14,15-EET↓/StAR/allopregnanolone/δGABAAR signaling-reversed normal thalamic inhibition | B, R | 37 | ||
| PWMT (FBP, 7–28 days, n=10) | HIF-1α/SDF1/CXCR4 signalling-microglia-astrocytes-neurons interactions. | B, R | 35 | ||
| PWMT (FBP, 7–28 days, n=8) | Spinal neuronal MCP-1 as a distant trigger for central sensitisation | B, R | 53 | ||
| PWMT (FBP, 7–28 days, n=7) | Inflammation and apoptosis | B, R | 27 | ||
| PWMT\PWTL (FBP,7, 14 days, n=5), | Chronic melatonin administrations↓ stimulating complex I and IV activities | B, R | 85 | ||
| Right VPL 25 µL autologous blood | PWMT (FBP 1–21 days, n=7), PWTL (no changes) | MiR-133b-3p/purinergic P2X4 receptors↓ in VPL | Not clarified | 32 | |
| PWMT (FBP, 1–21 days, n=8–14), PWTL (no changes) | P2X4 receptor↑ in microglia of thalamic perilesional tissues | R | 36 | ||
| Right VPM/VPL Coll IV (0.125U) | PWMT (FCP, 7–35 days, n=25), PWTL (7–35 days, n=25) | Activation of P2X7 receptors on microglia and BDNF and IL1β-glutamate. | Not clarified | 43 | |
| Right VBC Coll IV (0.125U) | PWMT (FBP, 7–35 days, n=8), PWTL (FBP, 21–49 days, n=8), Rotarod tests (no changes) | The noxious response in the medial thalamus and the alteration of the oscillation pattern of the thalamocortical pathway | B, R | 40 | |
| PWMT/ PWTL (FBP, 7–35 days, n=6–10) | The brain’s pain matrix and spinothalamocortical pathway | R | 86 | ||
| Right VBC and posterior thalamic nucleus Coll IV (0.025U) | PWMT (FBP, 7–21 days, n=6–8) | α2δ−1 subunit↑ in the thalamus and the dorsal horn | R | 52 | |
| CD1 mice | Right VPL Coll IV (0.07U) | PWMT (FCP, 3 days, n=8), tail suspension test (21–28 days, n=8) | Mediator complex subunit 1/BDNF/TrkB pathway | B, R | 87 |
| Right VPM and VPL Coll IV (0.01U/10 µL saline) | PWMT (FBP, 1–14 days, n=8), PWTL/cold pain (1–14 days, n=8) | TLR4/NF-κB/ERK1/2 in microglia | B | 33 | |
| PWMT/PWTL/cold pain (FCP, 1–28 days, n=10) | The protein–protein collaboration between neuronal nitric oxide synthase and postsynaptic density protein 95 in the thalamus | B | 38 | ||
| C57BL/6J mice | VPM and VPL (right/left) Coll IV (0.075 U) | Bederson score, von Frey test, thermal plate test | Inhibition of Panx1 attenuated proinflammatory factors transcription and neurite disassembly | R | 88 |
| Rhesus macaques | VPL (right/left) Coll IV (200 U/mL saline) | PWMT (FCP, 56 days, n=6) | Neuronal morphology alteration, including ipsilateral—PIC/SII synaptic loss | B | 28 |
| PWMT (FCP, 56–84 days, n=4), PWTL (FCP, 28–84 days, n=4) | Microglia-astrocyte interaction-abnormal excitability of surviving neurons | B | 39 | ||
| Japanese monkeys | Left VPL Coll IV (0.8U/site) | PWMT (FCP, 43 days/98–119 days), PWTL (FCP, 98–119 days), cold pain (FCP) (n=2) | Functional connectivity↑ between mediodorsal nucleus of the thalamus and amygdala | B | 34 |
| Macaca mulatta | VPL (right/left) Coll IV | PWMT (FCP, 63–273 days, n=5) | Cortical activity↑ | B | 41 |
BDNF, brain-derived neurotrophic factor; Coll, collagenase; Contra, hind paw contralateral; CPSP, central poststroke pain; CXCR4, C-X-C chemokine receptor type 4; 14,15-EET, 14,15-Epoxyeicosatrienoic acid; ERK, extracellular signal-regulated kinase; FBP, frequency bilateral pain; FCP, frequency contralateral pain; HIF-1α, hypoxia inducible factor 1α; MCP-1, Monocyte Chemoattractant Protein-1; NLRP3, NOD-like receptor family, pyrin domain containing 3; OFT, Open field test; PIC, posterior insular cortex; PWMT, paw-withdrawal mechanical threshold; PWTL, paw-withdrawal thermal latency; SDF1, stromal cell-derived factor 1; SII, secondary somatosensory cortex; StAR, steroidogenic acute regulatory protein; TLR4, Toll-like receptor 4; TrkB, neurotrophic receptor tyrosine kinase 2; VBC, ventral basal complex; VPL, ventral posterolateral nucleus; VPM, ventral posteromedial nucleus; δGABAAR, δ-subunit gamma-aminobutyric acid A receptor.