scholarly journals Role of purinergic signaling in experimental pneumococcal meningitis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marco Zierhut ◽  
Susanne Dyckhoff ◽  
Ilias Masouris ◽  
Matthias Klein ◽  
Sven Hammerschmidt ◽  
...  
Keyword(s):  
Pneumococcal Meningitis ◽  
Purinergic Signaling ◽  
Experimental Pneumococcal Meningitis

The role of complement in inflammation during experimental pneumococcal meningitis

1986 ◽  
Vol 1 (1) ◽  
pp. 15-32 ◽  
Author(s):  
Elaine Tuomanen ◽  
Bruno Hengstler ◽  
Oto Zak ◽  
Alexander Tomasz
Keyword(s):  
Pneumococcal Meningitis ◽  
Experimental Pneumococcal Meningitis

Protective role of NF-κB1 (p50) in experimental pneumococcal meningitis

2004 ◽  
Vol 498 (1-3) ◽  
pp. 315-318 ◽  
Author(s):  
Stefan Kastenbauer ◽  
Uwe Koedel ◽  
Falk Weih ◽  
Löms Ziegler-Heitbrock ◽  
Hans-Walter Pfister
Keyword(s):  
Pneumococcal Meningitis ◽  
Protective Role ◽  
Experimental Pneumococcal Meningitis

Role of Caspase-1 in experimental pneumococcal meningitis: Evidence from pharmacologic Caspase inhibition and Caspase-1-deficient mice

2002 ◽  
Vol 51 (3) ◽  
pp. 319-329 ◽  
Author(s):  
Uwe Koedel ◽  
Frank Winkler ◽  
Barbara Angele ◽  
Adriano Fontana ◽  
Richard A. Flavell ◽  
...  
Keyword(s):  
Pneumococcal Meningitis ◽  
Caspase 1 ◽  
Caspase Inhibition ◽  
Deficient Mice ◽  
Experimental Pneumococcal Meningitis

Corrigendum to “Protective role of NF-κB1 (p50) in experimental pneumococcal meningitis” [Eur. J. Pharmacol. 498 (2004) 315–318]

2004 ◽  
Vol 504 (3) ◽  
pp. 235
Author(s):  
Stefan Kastenbauer ◽  
Uwe Koedel ◽  
Falk Weih ◽  
Löms Ziegler-Heitbrock ◽  
Hans-Walter Pfister
Keyword(s):  
Pneumococcal Meningitis ◽  
Protective Role ◽  
Experimental Pneumococcal Meningitis

scholarly journals A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 278-279
Author(s):  
M Defaye ◽  
N Abdullah ◽  
M Iftinca ◽  
C Altier
Keyword(s):  
Chronic Pain ◽  
Central Sensitization ◽  
Microglial Activation ◽  
Visceral Pain ◽  
Purinergic Signaling ◽  
Designer Drugs ◽  
Visceral Afferents ◽  
Peripheral Sensitization ◽  
Specific Expression

Abstract Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown. Aims To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain. Methods We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation. Results Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation. Conclusions Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients. Funding Agencies CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship

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