HSPA1A can alleviate CFA-induced inflammatory pain by modulating macrophages
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE304075 | GEO | 2025/07/31
REPOSITORIES: GEO
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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.
2025-07-30 | PXD066909 |
Project description:HSPA1A can alleviate CFA-induced inflammatory pain by modulating macrophages
| PRJNA1298869 | ENA
Project description:Although several underlying pathophysiological processes have been explored, the origin and precise pathomechanism of migraine are still being debated. Inflammatory pathways have been suggested to play role in migraine, trigeminal nociceptor sensitisation, thereby causing hyperalgesia and allodynia. The aim of the present study was to investigate gene expression changes in trigeminal ganglia (TRG), central trigeminal nucleus caudalis (TNC) and peripheral blood mononuclear cells (PBMC) evoked by Complete Freund’s Adjuvant (CFA) induced peripheral inflammation. 512 differentially expressed genes were found between CFA-treated and contralateral TRG samples 7 days after CFA injection. The mRNA expression changes of G-protein coupled receptor 39 (Gpr39), kisspeptin-1 receptor (Kiss1r), kisspeptin (Kiss1) and Lkaaear1 were selected for validation. They were most upregulated on day 3 in TRGs of the CFA-treated side. CFA-induced significant orofacial mechanical allodynia in one day with a maximum on day 3. This correlated with patterns of neuronal (Fosb), glial (Iba1), and astrocyte (Gfap) activation markers in both TRG and TNC, and surprisingly in PBMCs. Similar transcriptional changes of Cgrp, the well-known key molecule in migraine pathophysiology, were also revealed. In TNCs, gene expression changes similar to TRGs were observed but Kiss1r transcripts were not significantly altered while Neurod2 was observed only in TNC. These results could indicate the involvement of Gpr39, Kiss1r and synaptic plasticity associated Lkaaear1, Neurod2 genes in the cascade of events resulting in the sensitization underlying migraine headache and the accompanying facial allodynia.
2018-12-14 | GSE111160 | GEO
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.
2010-10-07 | E-GEOD-24431 | biostudies-arrayexpress
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.
2010-10-07 | GSE24431 | GEO
Project description:Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP’s limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund’s adjuvant (CFA)-induced inflammatory pain against no treatment and vehicle controls.
2025-08-06 | GSE286589 | GEO
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.
2018-06-11 | E-MTAB-6864 | biostudies-arrayexpress
Project description:Inflammation-associated chronic pain is a global clinical problem, affecting millions of people worldwide. However, the underlying mechanisms that mediate inflammation-associated chronic pain remain unclear. A rat model of cutaneous inflammation induced by Complete Freund’s Adjuvant (CFA) has been widely used as an inflammation-induced pain hypersensitivity model. We present the transcriptomics profile of CFA-induced inflammation in the rat dorsal root ganglion (DRG) via an approach that targets gene expression, DNA methylation, and post-transcriptional regulation.
2021-05-19 | GSE174631 | GEO
Project description:Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, post-surgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute post-surgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively anti-allodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects. In addition, the selective NaV1.7 inhibitors ProTx-II and PF-04856264 as well as the clinical candidate CNV1014802 also reduced mechanical allodynia. Interestingly, co-administration of the opioid receptor antagonist naloxone completely reversed analgesic effects of Pn3a, indicating an involvement of endogenous opioids in the analgesic activity of Pn3a. Additionally, we found super-additive antinociceptive effects of sub-therapeutic Pn3a doses not only with the opioid oxycodone but also with the GABAB receptor agonist baclofen. Transcriptomic analysis of gene expression changes in dorsal root ganglia of mice post-surgery revealed decreased expression of several pro-nociceptive genes including N- and P/Q-type voltage-gated calcium channels important for neurotransmitter release, which suggest a reactive compensatory mechanism to reduce excessive pain similar to the endogenous opioid system. In summary, these findings suggest that pain after surgery can be successfully treated with NaV1.7 inhibitors alone or in combination with baclofen or opioids, which may present a novel and safe treatment strategy for this frequent and poorly managed condition.
2019-05-01 | GSE125076 | GEO
Project description:Temporomandibular joint (TMJ) osteoarthritis (OA) is a highly prevalent disorder affecting patient’s quality of life due to joint pain and dysfunction. A comprehensive understanding of cell type diversity and their dynamics of TMJ along joint degeneration and pain is lacking. Here we established an inflammatory TMJOA mouse model via intra-articular injection of CFA (Complete Freund’s Adjuvant). TMJOA mice exhibited OA and orofacial pain, recapitulating hallmark symptoms in patients. We performed single-cell transcriptomic profiling of TMJ followed by the validation. We revealed cellular diversity, anatomic position, and cell dynamics of TMJ at single cell resolution along the joint degeneration and pain.
2025-04-02 | GSE267942 | GEO