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

Central post-stroke pain (CPSP) is a severe chronic neuropathic pain syndrome that is a direct result of cerebrovascular lesions affecting the central somatosensory system. The pathogenesis of this condition remains unclear owing to its extensive clinical manifestations. Nevertheless, clinical and animal experiments have allowed a comprehensive understanding of the mechanisms underlying CPSP occurrence, based on which different theoretical hypotheses have been proposed. We reviewed and collected the literature and on the mechanisms of CPSP by searching the English literature in PubMed and EMBASE databases for the period 2002-2022. Recent studies have reported that CPSP occurrence is mainly due to post-stroke nerve injury and microglial activation, with an inflammatory response leading to central sensitization and de-inhibition. In addition to the primary injury at the stroke site, peripheral nerves, spinal cord, and brain regions outside the stroke site are involved in the occurrence and development of CPSP. In the present study, we reviewed the mechanism of action of CPSP from both clinical studies and basic research based on its sensory pathway. Through this review, we hope to increase the understanding of the mechanism of CPSP.

[High myopia and retinal ultrastructure of albino guinea-pigs].

OBJECTIVE: To explore the relationship between melanin synthesis and the congenital high myopia of albino guinea-pigs. METHODS: Twelve albino guinea-pigs and 12 pigmented guinea-pigs of 220~250 grams (aged 5~6 weeks) were chosen at random. The eyes were examined with retinoscopy, A-scan ultrasonography and vernier caliper. The retinal structures were examined with light and electronic microscope. RESULTS: The diopter was -19.17 D in albino guinea-pigs and +0.63 D in pigmented guinea-pigs on average. Compared with the pigmented guinea-pigs, the axial dimensions of the albino guinea-pigs were elongated. There was significant difference between the albino guinea-pigs and the pigmented guinea-pigs. The retinal thickness, pigment granules and membrane disc of the outer segment of the visual cells decreased in the albino guinea-pigs, and the membrane disc space became narrow. The normal retinal thickness, plenty of pigment granules , membrane disc and wide membrane disc space could be observed in the pigmented guinea-pigs. CONCLUSION: Albino guinea-pigs have high myopia, and pigmented guinea pigs have light hyperopia. There are structural differences in the retina between albino guinea-pigs and pigmented guinea-pigs. The abnormity of albino guinea-pigs provides optical foundation for its high myopia.

[Antisense c-fos oligonucleotides-induced myopia in guinea pigs].

OBJECTIVE: To characterize the antisense c-fos oligonucleotides that control the expression of immediate-early gene c-fos in retina in order to better understand the mechanism by which antisense c-fos oligonucleotides induced myopia. In this study the signal transduction in the pathway linking visual experience and the regulation of the eye's growth was investigated. METHODS: Thirty-one 3-week guinea pigs were assigned into 3 groups: antisense and sense c-fos oligonucleotides were intravitreally injected every 3 days to the eyes of the experimental guinea pigs at different concentrations; and saline vehicle to control guinea pigs in the same way. The refraction and axial length of the eyes were measured before and after the treatment, and the immediate-early gene c-fos expression in the retina was quantified by immunohistochemistry and RT-PCR. RESULTS: The moderate myopia was induced in high (1 nmol) and low (0.1 nmol) level of antisense c-fos oligonucleotide intravitreous injection (-5.425 D and -5.575 D, respectively) compared with the control ateral eyes. The refraction and axial length of the treated eyes increased, and the expression of immediate-early gene c-fos decreased significantly in the antisense c-fos oligonucleotides intravitreously injected eyes compared with the sense c-fos oligonucleotide intravitreously and saline vehicle injected eyes (P<0.01). The refraction and axial length were of no statistically significant differences among the sense c-fos oligonucleotides-treated eyes and saline-treated eyes and non-treated eyes (P>0.05). CONCLUSION: The obvious myopia can be induced by antisense c-fos oligonucleotides in guinea pigs; antisense c-fos oligonucleotides inhibit c-fos expression in the retina. Immediate-early gene c-fos may be a potential factor in the prevention of myopia and plays an important role in the signal transduction of the retina.

[Apoptosis and c-myc protein expression in the retinal of form-deprivation myopia].

OBJECTIVE: To study the apoptosis of retina and the expression of c-myc protein in form-deprivation myopia. METHODS: Two-day-old chickens were sutured with right eyelid for 4, 8 and 12 weeks. After measurement of refracation, the eyeballs were observed by light microscope and taken photos. Retinal apoptotic cells were measured by TUNEL staining and flow cytometry. C-myc protein were examined by immunohistochemistry and flow cytometry. RESULTS: Lacquer crack lesions were found in sutured eyes at 12 weeks. Apoptotic cells were observed in retinal outer and inner nuclear layer of the sutured eyes at 12 weeks and obvious peak of apoptosis was observed in sutured eyes at 12 weeks. The expression of c-myc protein was significantly more than control eyes at 8 and 12 weeks. CONCLUSION: The apoptosis of retinal was present in form-deprivation myopia with the degeneration of retina. C-myc protein plays an important role in retinal apoptosis of myopia.

[Dynamic expression of VIPR2 in form deprivation myopia].

OBJECTIVE: To investigate the dynamic expression and significance of vasoactive intestinal peptide receptor 2 (VIPR2) on retina-choroid-clera in high myopia. METHODS: Twenty-one yellow chicks of 1 day old were used in the research. The right eyes were the experimental group, covered continuously for 1 week, 2 weeks and 4 weeks respectively. The left eyes were not covered as the normal control group. Both groups were detected diopter degrees using retinoscopic refraction, determinated eyeball axis using ophthalmology ultra-A, and investigated VIPR2 expression on retina-choroid-sclera in both groups at three stages by SP immunohistochemical staining. RESULTS: The experimental eyes changed from hypermetropia at pre-experiment to high myopia during the experiment stages, and the diopter degrees were deeper and eyeball axis was longer along with the period of being covered. Both groups had strong expression of VIPR2 on photoreceptor-outer segment of the retina and choroids. The expression was down-regulated with the time in both groups. Compared with the control group, VIPR2 expression of the experimental group was significantly up-regulated (P < 0.05). CONCLUSION: Form deprivation could induce high myopia. The expression of VIPR2 existed on photoreceptor-outer segment of the retina and choroids. VIPR2 may play an important role on the formation and development of myopia.

[Dynamic changes of MMP-2 activity in the posterior sclera of chicks with form-deprivation myopia].

OBJECTIVE: To investigate the effect of form-deprivation on level of gelatinase in the posterior sclera in chicks. METHODS: Fifty 1-day-old chicks were monocularly deprived to establish the animal model of form-deprivation myopia (FDM). According to the duration of form-deprivation the experimental chicks were divided randomly and equivalently into 5 groups, which were deprived for 3, 7, 14, 21 and 30 days respectively. Meanwhile the other eyes of the deprived chicks were used as self-control groups and chicks of the same days were chosen randomly as the normal control groups for each FDM group. At each form-deprivation point the changes of degree of diopters and axial length of chicks in each group were recorded. The levels of gelatinase in posterior sclera of the experimental eyes were measured by gelatin enzymography. RESULTS: Compared with the normal and self-control groups, the levels of MMP-2 activity in FDM groups were much higher (P <0.01). With the increase of the time of monocular deprivation these changes became more significant and reached the top after 14 days' deprivation with an inter-group statistical difference (P <0.01). The dynamic changes of MMP-2 activity were the same as those of axial length and degree of diopters in each experimental groups. There was positive correlation between the MMP-2 activity and axial length (r = 0.989, P < 0.01). But there was a negative correlation between the MMP-2 activity and refractive degree. CONCLUSION: Increase of MMP-2 activity in the posterior sclera of chicks would be a direct key factor to trigger sclera ECM remodeling process in chick FDM.

[The treatment of retinal apoptosis by Caspase 3 inhibitor Ac-DEVD-CHO in experimental myopia].

OBJECTIVE: To investigate the mechanism of retinal apoptosis in chick experimental myopia and the therapy of Caspase 3 inhibitor Ac-DEVD-CHO. METHODS: Chick myopia was induced by lid-suture. After Ac-DEVD-CHO had been injected into vitreous, myopia was confirmed by optometry. Subsequently, chick eyeballs removed were measured its extro-dimensions, and the change of fundus were observed. Retinal apoptotic cells were determined by electron microscopy, TUNEL technique and flow cytometry. Retinal Caspase 3 proteins and its activities were measured by immunohistochemistry, flow cytometry and a colorimetric method using Ac-DEVD-pNA as a substrate. RESULTS: Ocular diopters and extro-diameters in all sutured eyes remarkly increased in comparison with its control eyes at 12 weeks after lid-suture. Lacquer crack lesions were found in 41 of 90 sutured eyes (45.56%). Apoptotic cells were observed in retinal outer and inner nuclear layer of the sutured eyes, and its apoptotic rate was significantly more than in control eyes (P < 0.05). Moreover, the expression of retinal Caspase 3 proteins and its activities were increased. After Ac-DEVD-CHO was injected into vitreous, the decrease of retinal apoptotic rate, Caspase 3 proteins and its activities was found. The treated effect of Ac-DEVD-CHO was in a dose dependent manner. CONCLUSIONS: Caspase 3 plays an important role in retinal apoptosis of chick myopia. Ac-DEVD-CHO can effectively ameliorate retinal apoptosis by blocked the effect of Caspase 3.

[Matrix metalloproteinase-2 mRNA expression in the posterior sclera of chick form-deprivation myopia].

OBJECTIVE: To investigate the dynamic changes of matrix metalloproteinase-2 (MMP-2) mRNA expression in the posterior sclera of chick form-deprivation myopia (FDM) and its possible molecular mechanism. METHODS: Fifty white 1-day-old leghorn chicks were divided randomly and equally into 5 groups. The right eye of each chick was covered with a plastic goggle at 4, 7, 14, 21, and 30 postborn days respectively to induce FDM, and the left eye served as a self-control. Meanwhile, normal age-matched chicks were provided as negative control speciments for each group. Removing the goggle at every experiment point, refractive status and axial length were determined with streak retinoscopy (without cycloplegia) and A-scan ultra-sonography under topical anaesthesia, respectively. Both eyes were collected after the chicks were killed. The total RNA in the posterior sclera was extracted traditionally using TRIZOL reagent, and then the expression levels of MMP-2 messenger RNA were analyzed by one step reverse transcriptiontase-polymerase chain reaction. RESULTS: Compared with the normal and self-control groups, the expression levels of MMP-2 mRNA in the deprived eyes significantly increased (P < 0.001). With the delay of form-deprivation duration, MMP-2 mRNA expression levels increased significantly and especially reached a highest point at the 14th day of monocular deprivation. After that the level decreased slightly, but maintained at a high level. Although there was no significant difference between the normal control group and the self-control one (P > 0.05), MMP-2 mRNA expressed slightly higher in the self-controlled eyes. CONCLUSION: As a primary element to trigger early active sclera extracellular matrix remodeling process, MMP-2 gene is probably involved in the development of FDM by excessive degradation of extraceller matrix which can make sclera thinner and the eye axis longer.