Central post-stroke pain (CPSP) is an intractable neuropathic pain, which can be caused by primary lesion of central somatosensory system. It is also a common sequelae of the thalamic hemorrhagic stroke (THS). So far, the underlying mechanisms of CPSP remain largely unknown. Our previous studies have demonstrated that SDF1-CXCR4 signaling in the hemorrhagic region contributes to the maintenance of the THS pain hypersensitivity via mediation of the thalamic neuroinflammation. But whether the spinal dorsal horn, an initial point of spinothalamic tract (STT), suffers from retrograde axonal degeneration from the THS region is still unknown. In this study, neuronal degeneration and loss in the spinal dorsal horn were detected 7 days after the THS caused by intra-thalamic collagenase (ITC) injection by immunohistochemistry, TUNEL staining, electron microscopy, and extracellular multi-electrode array (MEA) recordings, suggesting the occurrence of secondary apoptosis and death of the STT projecting neuronal cell bodies following primary THS via retrograde axonal degeneration. This retrograde degeneration was accompanied by secondary neuroinflammation characterized by an activation of microglial and astrocytic cells and upregulation of SDF1-CXCR4 signaling in the spinal dorsal horn. As a consequence, central sensitization was detected by extracellular MEA recordings of the spinal dorsal horn neurons, characterized by hyperexcitability of both wide dynamic range and nociceptive specific neurons to suprathreshold mechanical stimuli. Finally, it was shown that suppression of spinal neuroinflammation by intrathecal administration of inhibitors of microglia (minocycline) and astrocytes (fluorocitrate) and antagonist of CXCR4 (AMD3100) could block the increase in expression levels of Iba-1, GFAP, SDF1, and CXCR4 proteins in the dorsal spinal cord and ameliorate the THS-induced bilateral mechanical pain hypersensitivity, implicating that, besides the primary damage at the thalamus, spinal secondary damage and neuroinflammation also play the important roles in maintaining the central post-THS pain hypersensitivity. In conclusion, secondary neuronal death and neuroinflammation in the spinal dorsal horn can be induced by primary thalamic neural damage via retrograde axonal degeneration process. SDF1-CXCR4 signaling is involved in the mediation of secondary spinal neuroinflammation and THS pain hypersensitivity. This finding would provide a new therapeutic target for treatment of CPSP at the spinal level.

Background: Clear aligners create an aligner–tooth interface that may retain saliva, microorganisms, and dietary substrates. Evidence linking interface properties, oral microecological responses, and preventive interventions remains fragmented. Objective: To map and synthesize evidence on clear aligner interface properties and microbial adhesion, oral microbial ecology during clear aligner wear, and strategies for biofilm control and caries-risk mitigation. Methods: Following Joanna Briggs Institute methodology and PRISMA-ScR guidance, PubMed, Embase, and Web of Science Core Collection were searched from inception to August 31, 2026, without language restrictions. Backward and forward citation searching supplemented database searches. Original clinical, in vitro , and ex vivo studies involving active clear aligner treatment, associated materials or interfaces, or clear-aligner-specific interventions were eligible when they reported microbial, biofilm, microbiome, metabolomic, caries-related, or mineral outcomes. Two reviewers independently screened records; two authors charted and verified data. Findings were synthesized descriptively within three evidence domains. Results: Of 988 records, 132 reports were included. Because reports could contribute to more than one domain, 62 informed interface properties and microbial adhesion, 47 oral microbial ecology during wear, and 76 biofilm control and caries-risk mitigation. No single polymer, manufacturing method, or surface parameter consistently predicted microbial adhesion or biofilm formation. Outcomes reflected interactions among material characteristics, local topography, salivary conditioning, aging and exposure, microbial species, and experimental models. Clinical microbial responses were compartment- and time-dependent. Salivary and tooth-associated communities often remained relatively stable at the community level, whereas the inner aligner surface sometimes exhibited localized taxonomic, functional, metabolic, and pH-related changes. Investigated interventions included cleaning, antimicrobial and antifouling interface modifications, anticaries and remineralizing approaches, probiotics, and environment-responsive systems. Although many strategies reduced microbial burden, biofilm-related outcomes, acidogenicity, or mineral loss under tested conditions, evidence was predominantly short-term and preclinical. Assessments of durability, material performance, and safety were heterogeneous. Conclusions: Clear aligner–microbiota interactions appear context-dependent rather than uniformly favorable or unfavorable. Evidence neither establishes causal relationships between interface or microecological changes and clinical disease nor identifies a universally superior intervention. More standardized, clinically representative evidence may clarify their clinical relevance and inform preventive management during clear aligner treatment.