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NAMPT/NAD + /PARP1 Pathway Regulates CFA-Induced Inflammatory Pain via NF-κB Signaling in Rodents.
- Source :
-
Advanced biology [Adv Biol (Weinh)] 2024 May; Vol. 8 (5), pp. e2400028. Date of Electronic Publication: 2024 Mar 11. - Publication Year :
- 2024
-
Abstract
- Emerging evidence has implicated nicotinamide adenine dinucleotide (NAD <superscript>+</superscript> ) metabolism in various inflammatory diseases. In the study, the role of NAD <superscript>+</superscript> metabolism in Complete Freund's Adjuvant (CFA)-evoked inflammatory pain and the underlying mechanisms are investigated. The study demonstrated that CFA induced upregulation of nicotinamide phosphoribosyltransferase (NAMPT) in dorsal root ganglia (DRG) without significant changes in the spinal cord. Inhibition of NAMPT expression by intrathecal injection of NAMPT siRNA alleviated CFA-induced pain-like behavior, decreased NAD <superscript>+</superscript> contents in DRG, and lowered poly-(ADP-ribose) polymerase 1 (PARP1) activity levels. These effects are all reversed by the supplement of nicotinamide mononucleotide (NMN). Inhibition of PARP1 expression by intrathecal injection of PARP1 siRNA alleviated CFA-induced pain-like behavior, while elevated NAD <superscript>+</superscript> levels of DRG. The analgesic effect of inhibiting NAMPT/NAD <superscript>+</superscript> /PARP1 axis can be attributed to the downregulation of the NF-κB/IL-1β inflammatory pathway. Double immunofluorescence staining showed that the expression of NAMPT/NAD <superscript>+</superscript> /PARP1 axis is restricted to DRG neurons. In conclusion, PARP1 activation in response to CFA stimulation, fueled by NAMPT-derived NAD <superscript>+</superscript> , mediates CFA-induced inflammatory pain through NF-κB/IL-1β inflammatory pathway.<br /> (© 2024 Wiley‐VCH GmbH.)
- Subjects :
- Animals
Male
Mice
Freund's Adjuvant
Inflammation metabolism
Cytokines metabolism
Pain metabolism
NF-kappa B metabolism
Nicotinamide Phosphoribosyltransferase metabolism
Nicotinamide Phosphoribosyltransferase genetics
Ganglia, Spinal metabolism
Ganglia, Spinal drug effects
NAD metabolism
Poly (ADP-Ribose) Polymerase-1 metabolism
Poly (ADP-Ribose) Polymerase-1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2701-0198
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Advanced biology
- Publication Type :
- Academic Journal
- Accession number :
- 38463014
- Full Text :
- https://doi.org/10.1002/adbi.202400028