A light-responsive monocyte subset reprogrammed by danger signals to suppress pathological pain
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE306021 | GEO | 2025/08/27
REPOSITORIES: GEO
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Project description:A light-responsive monocyte subset reprogrammed by danger signals to suppress pathological pain
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Project description:Analyse of gene expression modification after chronic analgesic treatment. The hypothesis tested in the present study was that oxycodone and morphine induced gene expression modification. Results provide important information to understand the analgesic effects of oxycodone as compared to morphine in a neuropathic pain model Total RNA obtained from DRG of neuropathic or control animals after oxycodone or morphine treatment
2014-01-09 | E-GEOD-53897 | biostudies-arrayexpress
Project description:Analyse of gene expression modification after chronic analgesic treatment. The hypothesis tested in the present study was that oxycodone and morphine induced gene expression modification. Results provide important information to understand the analgesic effects of oxycodone as compared to morphine in a neuropathic pain model
2014-01-09 | GSE53897 | GEO
Project description:Neuropathic pain (NP) is a complex chronic pain due to the nervous system damage or diseases.Yuan-Hu Zhi Tong Prescription (YZP) is a well-known Traditional Chinese Medicine (TCM) formula for pain relief, which is composed of Corydalis Rhizoma (Yuanhu, YH) and Angelicae Dahuricae Radix (Baizhi, BZ). However, understanding of the analgesic and compatibility mechanisms of YZP remains limited. The present study found that YZP was more effective in relieving mechanical allodynia and thermal hypersensitivity than YH and BZ administered alone. To understand the potential analgesic and compatibility mechanisms of YZP on neuropathic pain (NP), RNA-seq and bioinformatics analyses were performed. The results revealed that YZP exerts analgesic effects mainly by relieving inflammation in the spinal cord through various mechanisms, such as suppressing leukocyte activation and cytokine-mediated signaling pathways. Moreover, YZP can relieve NP by modulating the neuropeptide signaling pathway and promoting damaged tissue regeneration. In terms of compatibility, YH and BZ demonstrated synergistic effects on the inflammatory response and neuropeptide signaling pathway. Furthermore, BZ was found to regulate calcium ion transport and promote skeletal muscle tissue regeneration, thereby alleviating concomitant symptoms of NP. Hub genes such as Ucn, Ptgs2, Gal, and others may play a pivotal role in YZP analgesia and the synergistic effects of YH-BZ compatibility.
2024-11-11 | GSE245768 | GEO
Project description:Background and aims: Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods: This was a double-blind, randomized, parallel-group, multi-center study in patients with sym- metric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years. Concomitant treatment with neuropathic pain medications (e.g. anticon- vulsants, tricyclic antidepressants, serotonin-noradrenaline uptake inhibitors, opioids, topical lidocaine or capsaicin) was not allowed. 134 patients with PDN were equally randomized to 28 days oral admin- istration of 20 mg AZD2423, 150 mg AZD2423, or placebo. The primary efficacy variable was the change of average pain score from 5-days baseline to the last 5 days of treatment, measured with numerical rating scale (NRS, 0–10). The secondary efficacy measures included NRS worst pain scores, patient global impression of change, pain interference on sleep and activity, and neuropathic pain symptom inventory (NPSI). Results: The change of NRS average pain score was not significantly different between treatment groups (AZD2423 20 mg: −1.50; AZD2423 150 mg: −1.35; placebo: −1.61). The NPSI total score and three out of five subscores (evoked pain, pressing/deep pain and paresthesia/dysesthesia) tended to be reduced more by AZD2423 150 mg than by placebo. No other secondary efficacy variables differed between treatment groups. The frequency and type of adverse events for AZD2423 were similar to placebo. The achieved plasma levels of AZD2423 in the two dose groups were in line with predictions from pharmacokinetic data previously obtained in healthy volunteers. Dose-dependent increase of plasma levels of the ligand of CCR2 (CCL2; chemokine ligand 2) and decrease of the mean levels of monocytes (−27% by AZD2423 150 mg) suggested that the administrated doses of AZD2423 interacted with the CCR2 target. Conclusion: The CCR2-antagonist AZD2423 showed no analgesic efficacy in PDN based on NRS average pain scores and global and functional pain outcome measures. The NPSI data suggested possible effects on certain sensory components of pain. There were no major safety or tolerability concerns.
2025-07-16 | GSE302658 | GEO
Project description:BVAC-B is immunotherapeutic vaccine using B-Cell and Monocytes as antigen presenting cell. This study is Open-label, Accelerated titration, Multiple dosing study to evaluate the safety, tolerability, immune response and pre-efficacy of BVAC-B in patients with progressive or recurrent HER2/neu positive gastric cancer after failure to standard care. 9-27 patients will be enrolled.
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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:Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6Chi blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear. Here, using a variety of in vivo murine models and orthogonal approaches, including surgical myocardial infarction, splenectomy, parabiosis, cell adoptive transfer, lineage tracing and cell tracking, RNA sequencing, and functional characterization, we establish in mice an essential role for splenic CD169+Tim4+ marginal metallophilic macrophages (MMMs) in post-MI wound healing. Splenic CD169+Tim4+ MMMs circulate in blood as Ly6Clow monocytes expressing macrophage markers and help populate CD169+Tim4+CCR2-LYVE1low macrophages in the naïve heart. After acute MI, splenic MMMs augment phagocytosis, CCR3 and CCR4 expression, and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169+Tim4+LyVE1low macrophages with an immunomodulatory and pro-resolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Liver X receptor-a agonist-induced expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling. Finally, humans with acute ST-elevation MI also exhibit expansion of circulating CD169+Tim4+ cells, primarily within the intermediate (CD14+CD16+) monocyte population. We conclude that splenic CD169+Tim4+ MMMs are required for pro-resolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure.
2025-06-18 | GSE289921 | GEO
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.
2025-07-31 | GSE304075 | GEO
Project description:In this study, blood was collected from human participants with osteoarthritis pain, along with radiographic scores (Kellgren & Lawrence Score (KL)) and pain scores (Numerical Rating Scale (NRS)). Peripheral blood mononuclear cells were isolated from whole blood, and classical and intermediate monocytes were further isolated using fluorescence-activated cell sorting. mRNA was then extracted from monocytes for sequencing.
2024-12-31 | E-MTAB-14402 | biostudies-arrayexpress