Infrapatellar fat pad-derived MSC response to inflammation and fibrosis induces an immunomodulatory phenotype involving CD10-mediated Substance P degradation DOI Creative Commons
Dimitrios Kouroupis,

Annie C. Bowles,

Melissa A. Willman

et al.

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: July 26, 2019

The infrapatellar fat pad (IFP) serves as a reservoir of Mesenchymal Stem Cells (MSC), and with adjacent synovium plays key roles in joint disease including the production Substance P (SP) affecting local inflammatory responses transmitting nociceptive signals. Here, we interrogate human IFP-derived MSC (IFP-MSC) reaction to pro-fibrotic environments (cell priming by TNFα/IFNγ TNFα/IFNγ/CTGF exposure respectively), compared bone marrow-derived (BM-MSC). Naïve IFP-MSC exhibit increased clonogenicity chondrogenic potential BM-MSC. Primed cells experienced dramatic phenotypic changes, sharp increase CD10, upregulation immunomodulatory transcripts, secreted growth factors/cytokines pathways (IL-10, TNF-α, MAPK, Ras PI3K-Akt). Naïve, more so primed (both) induced SP degradation vitro, reproduced their supernatants abrogated thiorphan, CD10 inhibitor. These findings were vivo rat model acute synovitis, where transiently engrafted reduction. Functionally, demonstrated sustained antagonism activated peripheral blood mononuclear (PBMC) proliferation, significantly outperforming declining dose-dependent effect naïve cohorts. Collectively, our vitro data supports cell way enhance immunoregulatory properties IFP-MSC, which selectively engraft areas active synovitis/IFP fibrosis inducing degradation, resulting cell-based product alternative BM-MSC potentially treat degenerative/inflammatory diseases.

Language: Английский

Mechanisms of Transmission and Processing of Pain: A Narrative Review DOI Open Access
Girolamo Di Maio, Ines Villano, Ciro Rosario Ilardi

et al.

International Journal of Environmental Research and Public Health, Journal Year: 2023, Volume and Issue: 20(4), P. 3064 - 3064

Published: Feb. 9, 2023

Knowledge about the mechanisms of transmission and processing nociceptive information, both in healthy pathological states, has greatly expanded recent years. This rapid progress is due to a multidisciplinary approach involving simultaneous use different branches study, such as systems neurobiology, behavioral analysis, genetics, cell molecular techniques. narrative review aims clarify pain while also taking into account characteristics properties nociceptors how immune system influences perception. Moreover, several important aspects this crucial theme human life will be discussed. Nociceptor neurons play key role inflammation. The interactions between occur within peripheral sites injury central nervous system. modulation nociceptor activity or chemical mediators may provide promising novel approaches treatment chronic inflammatory disease. sensory fundamental host's protective response, understanding its pivotal process revealing new strategies for pain.

Language: Английский

Citations

27
Influence of polyethylene terephthalate (PET) microplastic on selected active substances in the intramural neurons of the porcine duodenum DOI Creative Commons
Ismena Gałęcka, Natalia Szyryńska, Jarosław Całka

et al.

Particle and Fibre Toxicology, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 6, 2024

Abstract Background Currently, society and industry generate huge amounts of plastics worldwide. The ubiquity microplastics is obvious, but its impact on the animal human organism remains not fully understood. digestive tract one first barriers between pathogens xenobiotics a living organism. Its proper functioning extremely important in order to maintain homeostasis. aim this study was determine effect microplastic enteric nervous system histological structure swine duodenum. experiment carried out 15 sexually immature gilts, approximately 8 weeks old. animals were randomly divided into 3 groups (n = 5/group). control group received empty gelatin capsules once day for 28 days, research daily with polyethylene terephthalate (PET) particles as mixture various sizes (maximum particle size 300 µm) at dose 0.1 g/animal/day. second ten times higher—1 Results A 1 g/day/animal causes more changes Statistically significant differences expression cocaine amphetamine regulated transcript, galanin, neuronal nitric oxide synthase, substance P, vesicular acetylcholine transporter vasoactive intestinal peptide high noted. histopathological frequently observed pigs receiving higher PET. Conclusion Based it may be assumed, that oral intake might have potential negative influence tract, dose-dependent.

Language: Английский

Citations

14
Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway DOI Creative Commons

Jing Lan,

Ziteng Deng,

Qiuzhen Wang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(7), P. 2507 - 2531

Published: Jan. 1, 2024

Neuropeptide substance P (SP) belongs to a family of bioactive peptides and regulates many human diseases. This study aims investigate the role underlying mechanisms SP in colitis. Here, activated SP-positive neurons increased expression were observed dextran sodium sulfate (DSS)-induced colitis lesions mice. Administration exogenous efficiently ameliorated clinical symptoms, impaired intestinal barrier function, inflammatory response. Mechanistically, protected mitochondria from damage caused by DSS or TNF-α exposure, preventing mitochondrial DNA (mtDNA) leakage into cytoplasm, thereby inhibiting cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway. can also directly prevent STING phosphorylation through neurokinin-1 receptor (NK1R), activation TBK1-IRF3 signaling Further studies revealed that alleviated TNF-α-induced ferroptosis process, which was associated with repressing cGAS-STING Notably, we identified NK1R inhibition reversed effects on inflammation via Collectively, unveil attenuates suppressing mtDNA-cGAS-STING acting pathway, contributing improving an NK1R-dependent manner. These findings provide novel mechanism regulating ulcerative (UC) disease.

Language: Английский

Citations

13
Substance P’s Impact on Chronic Pain and Psychiatric Conditions—A Narrative Review DOI Open Access

Charles W. Humes,

Aleksandar Sič,

Nebojša Nick Knežević

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5905 - 5905

Published: May 28, 2024

Substance P (SP) plays a crucial role in pain modulation, with significant implications for major depressive disorder (MDD), anxiety disorders, and post-traumatic stress (PTSD). Elevated SP levels are linked to heightened sensitivity various psychiatric conditions, spurring interest potential therapeutic interventions. In chronic pain, commonly associated MDD emerges as key mediator emotional regulation. This review examines SP’s impact on perception its contributions MDD, PTSD. The association of increased conditions underscores importance modulation. Additionally, influences the pathophysiology PTSD, highlighting target. Understanding diverse effects provides valuable insights into mechanisms underlying these disorders their treatment. Further research is essential explore modulation develop more effective treatment strategies.

Language: Английский

Citations

10
Pain persists in mice lacking both Substance P and CGRPα signaling DOI Creative Commons
Donald Iain MacDonald, Monessha Jayabalan,

Jonathan Seaman

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 18, 2025

The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides their receptors are expressed at high levels in pain-responsive neurons from the periphery to brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve clinical trials. Since extensively co-expressed, we hypothesized that simultaneous inhibition would be required effective analgesia. We therefore generated Tac1 Calca double knockout (DKO) mice assessed behavior using a wide range of pain-relevant assays. As expected, were undetectable throughout nervous system DKO mice. To our surprise, animals displayed largely intact responses mechanical, thermal, chemical, visceral stimuli, as well itch. Moreover, chronic inflammatory neurogenic inflammation unaffected by loss two peptides. Finally, neuropathic evoked nerve injury or chemotherapy treatment was also preserved peptide-deficient Thus, results demonstrate even combination, transmission acute pain.

Language: Английский

Citations

1
Circadian rhythms and pain DOI
Jacob R. Bumgarner, William H. Walker, Randy J. Nelson

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2021, Volume and Issue: 129, P. 296 - 306

Published: Aug. 8, 2021

Language: Английский

Citations

56
Beyond CGRP: The calcitonin peptide family as targets for migraine and pain DOI Open Access
Tayla A. Rees, Erica R. Hendrikse, Debbie L. Hay

et al.

British Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 179(3), P. 381 - 399

Published: June 29, 2021

The CGRP system has emerged as a key pharmacological target for the treatment of migraine. However, some individuals who suffer from migraine have low or no response to anti‐CGRP other treatments, suggesting need additional clinical targets. belongs calcitonin family peptides, which includes calcitonin, amylin, adrenomedullin and 2. These peptides display range pro‐nociceptive anti‐nociceptive actions, in primary headache conditions such Calcitonin also show expression at sites relevant pain. This suggests that their receptors, beyond CGRP, may be therapeutically useful pain disorders. review considers localisation peripheral pathways discusses how they contribute LINKED ARTICLES article is part themed issue on Advances Migraine Headache Therapy (BJP 75th Anniversary). To view articles this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.3/issuetoc

Language: Английский

Citations

49
Innervation of the Human Intervertebral Disc: A Scoping Review DOI Open Access
Adam M.R. Groh, Dale E. Fournier, Michele C. Battié

et al.

Pain Medicine, Journal Year: 2021, Volume and Issue: 22(6), P. 1281 - 1304

Published: Feb. 12, 2021

Back pain is an elusive symptom complicated by a variety of possible causes, precipitating and maintaining factors, consequences. Notably, the underlying pathology remains unknown in significant number cases. Changes to intervertebral disc (IVD) have been associated with back pain, leading many postulate that IVD may be direct source typically referred as discogenic pain. Yet despite decades research into neuroanatomy IVD, there lack consensus literature distribution function neural elements within tissue. The current scoping review provides comprehensive systematic overview studies document topography, morphology, immunoreactivity humans.Articles were retrieved from six separate databases three-step search independently evaluated two reviewers.Three categories described IVD: perivascular nerves, sensory nerves independent blood vessels, mechanoreceptors. Nerves consistently localized outer layers annulus fibrosus. Neural ingrowth inner fibrosus nucleus pulposus was found occur only degenerative disease states.While pattern innervation clear, specific topographic arrangement context unclear.

Language: Английский

Citations

46
The two-faced effects of nerves and neuropeptides in corneal diseases DOI
Romina Mayra Lasagni Vitar, Paolo Rama, Giulio Ferrari

et al.

Progress in Retinal and Eye Research, Journal Year: 2021, Volume and Issue: 86, P. 100974 - 100974

Published: June 7, 2021

Language: Английский

Citations

45
PGE2/EP4 skeleton interoception activity reduces vertebral endplate porosity and spinal pain with low-dose celecoxib DOI Creative Commons
Peng Xue, Shenyu Wang,

Xiao Lyu

et al.

Bone Research, Journal Year: 2021, Volume and Issue: 9(1)

Published: Aug. 2, 2021

Abstract Skeletal interoception regulates bone homeostasis through the prostaglandin E2 (PGE2) concentration in bone. Vertebral endplates undergo ossification and become highly porous during intervertebral disc degeneration aging. We found that PGE2 was elevated to generate spinal pain. Importantly, treatment with a high-dose cyclooxygenase 2 inhibitor (celecoxib, 80 mg·kg −1 per day) decreased attenuated pain mice lumbar spine instability. However, this impaired formation endplates, recurred after discontinuing treatment. Interestingly, low-dose celecoxib (20 day, which is equivalent one-quarter of clinical maximum dosage) induced latent inhibition at 3 weeks post-treatment, persisted even Furthermore, when maintained physiological level celecoxib, endplate porosity reduced significantly, associated sensory nerve innervation These findings suggest may help maintain skeletal decrease vertebral porosity, thereby reducing mice.

Language: Английский

Citations

45