Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 119173 - 119173
Published: Nov. 1, 2024
Language: Английский
Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12
Published: July 29, 2024
Approximately one-third of the patients with diabetes worldwide suffer from neuropathic pain, mainly categorized by spontaneous and stimulus-induced pain. Microglia are a class immune effector cells residing in central nervous system play pivotal role diabetic pain (DNP). specifically respond to hyperglycemia along inflammatory cytokines adenosine triphosphate produced during hyperglycemic damage nerve fibers. Because presence multiple receptors on microglial surface, microglia dynamically highly responsive their immediate environment. Following peripheral sensitization caused hyperglycemia, affected cascade factors other substances accordingly, resulting change functional state for DNP pathogenesis. Inhibition such as P2X reporters, reducing cytokine expression levels reactivity mechanisms, inhibiting intracellular signaling pathways can effectively alleviate DNP. A variety drugs attenuate aforementioned processes induced reactivity. In this review, we summarize pathological mechanisms which promote maintain DNP, therapeutic techniques available, latest advances field.
Language: Английский
Citations
5
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 4, 2025
ABSTRACT The interaction between non-neuronal cells and nerve endings in the epidermis significantly influences development of various diseases, including Painful Diabetic Neuropathy (PDN). PDN is a common challenging complication diabetes, characterized by changes skin innervation accompanied neuropathic pain. While there growing evidence that epidermal cells, such as resident immune play crucial role progression PDN, underlying mechanisms this neuropathy remain poorly understood. In our studies, we utilized transgenic methods, pain behavioral assessments, single-cell RNA sequencing (scRNAseq) clinically relevant high-fat diet (HFD) mouse model biopsy samples from patients, to investigate Langerhans (LCs) condition. We observed an increased density LCs male mice coinciding with onset mechanical allodynia. Furthermore, found correlated small fiber degeneration HFD biopsies taken well-characterized patients compared healthy controls. Importantly, selective ablation using diphtheria-toxin strategy was prevent nociceptive behavior mice. This indicates are both necessary sufficient for allodynia spontaneous Interestingly, when were ablated female mice, it did not but rather promoted behavior, suggesting existence sex-specific mediated LCs. scRNAseq transcriptomic analysis paw which included males females, revealed significant sex-mediated differences expression specific target genes within model. identified differentially expressed associated axonal guidance responses Additionally, integrating data dorsal root ganglia (DRG) uncovered altered communication cutaneous afferents through Semaphorin-Plexin signaling pathways PDN. These findings highlight key contributors suggest their potential therapeutic targets innovative treatments, particularly topical therapies aimed at modulating cell activity neuroimmune skin. Our investigations indicate may different roles sensation under normal pathological conditions, underscores importance considering sex developing more effective treatments. BRIEF SUMMARY plays (PDN), diabetes. Using transcriptomics tissues these revealed, first time, dimorphic Single-cell related guidance, pathways.
Language: Английский
Citations
0
CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)
Published: Feb. 1, 2025
ABSTRACT Aims This study aimed to test the hypothesis that nuclear factor of activated T cells 1 (NFAT1) signaling contributes bone cancer pain by regulating interleukin (IL)‐18 expression in spinal microglia. Methods was performed on male mice using a Lewis lung carcinoma‐induced model. Nociceptive behaviors were evaluated measuring mechanical allodynia, thermal hyperalgesia, and spontaneous pain. Expression levels measured via real‐time quantitative polymerase chain reaction, western blotting, immunofluorescence analysis. The effect pharmacologic intervention NFAT1/IL‐18 primary outcome. Results NFAT1 upregulated microglia after tumor inoculation. Pharmacological inhibition upregulation prevented reversed cancer‐related behaviors. In microglia, decreased p38 MAPK phosphorylation IL‐18 production. Blocking suppressed tumor‐induced neuronal sensitization microglial activation as well N‐methyl‐D‐aspartate receptor subsequent Ca 2+ ‐dependent signaling. Conclusion Microglia NFAT1‐p38 through IL‐18‐mediated central could be potential target for therapeutic prevent
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3835 - 3835
Published: April 18, 2025
Chronic pain is an extremely prevalent healthcare issue that has a profound impact on individuals and society. Sex sex hormones regulate the threshold differently in males females processing. However, regulatory mechanisms of differences response to painful stimuli are still unclear, which contributes difficulty analgesic drug development. Interleukins mediate neuroinflammation involved development chronic pain. Recent studies have found regulation thresholds by interleukins. Most previous used male animals study effects treatments due complexity estrogen. This review summarizes only female or both sexes examine interleukin-regulated pain, provide theoretical basis for more targeted precision medicines
Language: Английский
Citations
0
Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 119173 - 119173
Published: Nov. 1, 2024
Language: Английский
Citations
0