Project description:Current clinical approaches for managing inflammatory pain are frequently accompanied by adverse effects, significantly compromising patients' quality of life. This study investigates the analgesic potential of murine HSPA1A protein administration in alleviating Complete Freund’s Adjuvant (CFA)-induced inflammatory pain. Findings indicate that HSPA1A mitigates CFA-induced mechanical allodynia positively correlated with macrophage abundance. Transcriptomic RNA sequencing suggests involvement of inflammation-associated pathways in plantar tissues after HSPA1A injection.
Project description:Current clinical approaches for managing inflammatory pain are frequently accompanied by adverse effects, significantly compromising patients' quality of life. This study investigates the analgesic potential of murine HSPA1A protein administration in alleviating Complete Freund’s Adjuvant (CFA)-induced inflammatory pain. Findings indicate that HSPA1A mitigates CFA-induced mechanical allodynia positively correlated with macrophage abundance.
Project description:Background: We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential to reduce osteoarthritic pain. The aim of this study was to identify genes altered in this model of osteoarthritic pain and use this information to infer analgesic potential of compounds based on their own gene expression profiles using the Connectivity Map approach. Results: Using microarrays, we identified differentially expressed genes in L4 and L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for 4 days compared to matched, untreated control animals. Analysis of these data indicated that the two groups were distinguishable by differences in genes important in immune responses, nerve growth and regeneration. This list of differentially expressed genes defined a âCFA signatureâ. We used the Connectivity Map approach to identify pharmacologic agents in the Broad Institute Build02 database that had gene expression signatures that were inversely related (ânegatively connectedâ) with our CFA signature. To test the predictive nature of the Connectivity Map methodology, we tested phenoxybenzamine (an alpha adrenergic receptor antagonist) â one of the most negatively connected compounds identified in this database - for analgesic activity in the CFA model. Our results indicate that at 10mg/kg, phenoxybenzamine demonstrated analgesia comparable to that of Naproxen in this model. Conclusion: Evaluation of phenoxybenzamine-induced analgesia in the current study lends support to the utility of the Connectivity Map approach for identifying compounds with analgesic properties in the CFA model. A naive (control) group of rats (n = 6) and a group of rats injected with CFA (n = 6) were used for gene expression profiling experiments. One animal from the control group did not yield sufficient amount of RNA for microarray and thus was omitted from further processing. In total, 5 microarrays each from the 5 animals in the control group, and 6 microarrays each from the 6 animals in the CFA group were analyzed.
Project description:Background: We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential to reduce osteoarthritic pain. The aim of this study was to identify genes altered in this model of osteoarthritic pain and use this information to infer analgesic potential of compounds based on their own gene expression profiles using the Connectivity Map approach. Results: Using microarrays, we identified differentially expressed genes in L4 and L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for 4 days compared to matched, untreated control animals. Analysis of these data indicated that the two groups were distinguishable by differences in genes important in immune responses, nerve growth and regeneration. This list of differentially expressed genes defined a “CFA signature”. We used the Connectivity Map approach to identify pharmacologic agents in the Broad Institute Build02 database that had gene expression signatures that were inversely related (‘negatively connected’) with our CFA signature. To test the predictive nature of the Connectivity Map methodology, we tested phenoxybenzamine (an alpha adrenergic receptor antagonist) – one of the most negatively connected compounds identified in this database - for analgesic activity in the CFA model. Our results indicate that at 10mg/kg, phenoxybenzamine demonstrated analgesia comparable to that of Naproxen in this model. Conclusion: Evaluation of phenoxybenzamine-induced analgesia in the current study lends support to the utility of the Connectivity Map approach for identifying compounds with analgesic properties in the CFA model.
Project description:We show here that the up-regulation of SUMO1-conjugated protein levels in a CFA-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels. We further demonstrate that hnRNPA1 binds to TRPA1 mRNA and its SUMOylation, up-regulated in CFA-induced inflammatory pain, contributes to stabilizing TRPA1 mRNA by accumulating hnRNPA1 in the cytoplasm.
Project description:Six different mouse pain models were studied: (1) tumour-injection model for bone cancer pain; (2) partial sciatic nerve ligation (PSL) for neuropathic pain; (3) mechanical joint loading for osteoarthritis pain; (4) oxaliplatin-induced painful neuropathy for chemotherapy-induced pain; (5) hyperalgesic priming model for chronic muscle pain; and (6) complete Freund’s adjuvant (CFA)-injection for inflammatory pain. Transcriptomic microarray analyses were performed using RNA isolated from dorsal root ganglia.
Project description:We show here that the up-regulation of SUMO1-conjugated protein levels in a CFA-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels.
Project description:The goal of this study was to evaluate the role of HDAC4 in spinal sensitization. We analyzed gene expression changes associated with the subcellular localization of HDAC4 in the spinal cord dorsal horn following CFA-induced inflammatory pain. The analysis was performed in basal conditions and after intraplantar injection of CFA to the hind paw of mice that received intraspinal injection of rAAV-constructs influencing the subcellular localization of HDAC4.
Project description:Purpose: In this study, we aimed to analyze lncRNA expression in the whole transcriptome of trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in a chronic inflammatory TMJ pain mouse model. Chronic inflammatory TMJ pain was induced by intra-TMJ injection of complete Freund's adjuvant (CFA). The lncRNA expression patterns in the whole transcriptome of TG and Sp5C were profiled with RNA sequencing.
Project description:To identify common mechanisms and targets regulating different types of pathological pain, we established models for neuropathic pain induced by spinal nerve ligation (SNL), inflammatory pain induced by complete Freund's adjuvant (CFA), chemotherapy pain induced by paclitaxel (PTX), and bone cancer pain induced by Lewis lung carcinoma (LLC) cells. We then collected dorsal root ganglion (DRG) tissues from mice for RNA-seq analysis.