Role of Sensory Pathway Injury in Central Post-Stroke Pain: A Narrative Review of Its Pathogenetic Mechanism

Figures & data

Figure 1 Anatomical schematic diagram of the sensory pathway (left). After stroke, the body corresponds to the possible range of CPSP (right).

Table 1 Clinical Study of Spinal Thalamic Tract Injury in Central Pain After Stroke

Author Year	Number of Patients	Type of Lesion	Localization of Lesion	Detection Method	Subjects Grouping	Results	Conclusion
Garcia-Larrea, Convers et al, 2002^Citation25	30	Wallenberg stroke	Brainstem Thalamo-cort	LEP	Unilateral neuropathic central pain VS lateralized pain of non-organic origin	LEPs significantly diminished after stimulation of painful areas	LEPs reflect deafferentation of spinothalamic afferents
Veciana, Valls-Solé et al, 2005^Citation26	7	Stroke	Lateral medulla	LEP	Affected side VS Non-affected side	LEPs were absent, markedly reduced and delayed	Spinothalamic tract lesions can be demonstrated by abnormal LEP on the affected side
Hong, Bai et al, 2010^Citation68	30	Intracerebral hemorrhage	Corona radiata and basal ganglia	DTT	CPSP VS Non-CPSP	DTT parameters: TV decreases, FA, MD remain unchanged	CPSP patients STP partially damaged
Hong, Choi et al, 2012^Citation32	52	Intracerebral hemorrhage	Corona radiata, basal ganglia and thalamus	DTT	STP Preserved VS STP Disrupted	Prevalence of CPSP 47% VS 17%	Partial STP injury is more likely to lead to CPSP than complete injury
Jang, Chang et al, 2017^Citation69	1	Intracerebral hemorrhage	Corpus Callosum	DTT	3-year VS 1-month postonset	STT had become thinner	Delayed central pain due to STT degeneration
Jang, Lee et al, 2017^Citation70	5	Cerebral infarction	Corona radiata, Thalamus, Pre- and post-central gyrus	DTT	CPSP VS control DTT	Parameters: TV, FA decreases and MD increases	STT injury may be the cause of CPSP in patients with cerebral infarction
Jang, Kim et al, 2018^Citation71	1	Intracerebral hemorrhage	Thalamus	DTT	14-month VS 2-week postonset	STT partial tearing and thinning	Late onset CPSP may be attributed to degenerative peripheral neurological changes in STT

Abbreviations: LEP, Laser evoked potentials; DTT, diffusion tensor tractography; TV, tract volume; FA, fractional anisotropy; MD, mean diffusivity; STP, spino-thalamo-cortical pathway; STT, spinothalamic tract.

Table 2 Molecular Mechanism Studies of CPSP

Author Year	Animal	Model	Molecules Cells	Mechanism
Infantino et al, 2022^Citation58	CD1 mice	TH	MED1/BDNF/TrkB microglia	Activation of microglia around thalamic injury and and depression-related molecules were expressed in hippocampus
Lu et al, 2021^Citation47	Sprague-Dawley rats	TH	P2X4R/TNF-a/TNFR1/GABAaR microglia	Elevated TNF-a levels around thalamic injury, surface GABAaR endocytosis
Fu, Du et al, 2021^Citation50	CD1 mice, C57BL/6J mice	TH	FTO/TLR4 neurons	FTO participates in the occurrence of CPSP by stabilizing the up-regulation of TLR4 in thalamic neurons
Hiraga, Itokazu et al, 2020^Citation44	C57BL/6J mice	TH	_microglia	The microglia in the damaged thalamus and ipsilateral primary sensory cortex were activated, and lesion-induced neural network reorganization occurred
Huang, Fu et al, 2020^Citation72	CD1 male mice	TH	Fgr/NF-ΚB, ERK/TNF-α microglia	The increase of Fgr in the damaged part of thalamus mediates the up-regulation of inflammatory factor TNF-αand participates in the production and maintenance of CPSP
Chen et al, 2019^Citation55	Sprague-Dawley rats	TH	AP/δGABAaR neurons^Citation45	Reduced concentration of AP in the VPL and downregulation of δGABAAR expression in the medial thalamus
Cai et al, 2018^Citation56	CD1 mice	TH	PSD-95 /nNOS neurons	Protein-protein interactions between PSD-95 and thalamic nNOS mediate CPSP production
Yang et al, 2017^Citation18	Sprague-Dawley rats	TH	SDF1/CXCR4 astrocytes/ microglia	SDF1 binds to CXCR4 around thalamic injury and mediates microglial-astrocyte neuronal interactions and release of pro-inflammatory mediators
Shih, Kuan et al, 2017^Citation73	Sprague Dawley rats	TH	P2X4R/BDNF microglia	P2X4R leads to phosphorylation of p38 mitogen-activated protein kinase, allowing BDNF release leading to CPSP
Y. Yang et al, 2016^Citation53	Sprague–Dawley rats	TH	a2d-1 subunit neurons	Upregulation of a2d-1 on thalamic and spinal cord neurons early in CPSP
Kuan, Shih et al, 2015^Citation48	Sprague–Dawley rats	TH	P2X7R/ IL-1β microglia	P2X7R promotes downstream secretion of IL-1β and contributes to hyperexcitability of neurons, leading to CPSP

Abbreviations: TH, Thalamic hemorrhage; MED1, Mediator Complex Subunit 1; BDNF, Brain Derived Neurotrophic Factor; TrkB, tropomyosin receptor kinase B; P2X4R, P2X4 receptors; TNF, tumor necrosis factor; (δ)GABAaR, (δ-subunit) gamma-aminobutyric acid A receptors; ERK, extracellular regulated protein kinases; FTO, fat-mass and obesity-associated protein; TLR4, Toll-like receptor 4; AP, allopregnanolone; PSD-95, postsynaptic density protein 95; nNOS, neuronal nitric oxide synthase; SDF1, stromal cell-derived factor 1; CXCR4, Chemokine receptors 4; P2X7R, P2X7 receptors; IL-1β, interleukin-1β.

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