Whole Blood Transcriptome Analysis in Patients with Trigeminal Neuralgia: a Prospective Clinical Study.

Trigeminal neuralgia (TN) brings a huge burden to patients, without long-term effective treatment. This study aimed to explore the differentially expressed genes (DEGs) and related enrichment pathways in patients with TN. This was a study of transcriptome sequencing and bioinformatics analysis of human samples. Whole blood samples were collected from the TN patients and pain-free controls. RNA was extracted to conduct the RNA-sequencing and the subsequent bioinformatics analysis. DEGs between the two groups were derived. Kyoto encyclopedia of genes and genomes (KEGG) and Gene ontology (GO) was used to find the enrichment pathways of DEGs. Protein protein interaction (PPI) network was used to depict the interaction between DEGs and find the most important gene, hub gene. Compared with the control group, there were 117 up-regulated DEGs and 103 down-regulated DEGs in the whole blood of patients in the TN group. Pathway enrichment analysis showed that DEGs were mainly enriched in the neuroimmune and metabolic pathways. The PPI network demonstrated that colony stimulating factor 2 (CSF2) was the most important hub gene in the whole blood of TN patients. This study shows the expression of the transcriptome in the whole blood samples of TN patients. The neuroimmune responses and key hub gene CSF2 in the whole blood cells play a vital role in the occurrence of TN. Our research provides a theoretical basis for the diagnosis and treatments of TN. This study was registered at clinicaltrials.gov in June 2021 (No. NCT04923399).

The CSF1-CSF1R pathway in the trigeminal ganglion mediates trigeminal neuralgia via inflammatory responses in mice.

BACKGROUND: Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. METHODS: Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. RESULTS: The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. CONCLUSIONS: The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.

The modified lymphocyte C-reactive protein score is a promising indicator for predicting 3-year mortality in elderly patients with intertrochanteric fractures.

BACKGROUND: Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery. METHODS: A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743-16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit. CONCLUSIONS: mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.