CTRP9 attenuates peripheral nerve injury-induced mechanical allodynia and thermal hyperalgesia through regulating spinal microglial polarization and neuroinflammation mediated by AdipoR1 in male mice.
Animals
Male
Receptors, Adiponectin
/ metabolism
Microglia
/ metabolism
Hyperalgesia
/ metabolism
Mice
Adiponectin
/ metabolism
Peripheral Nerve Injuries
/ complications
Mice, Inbred C57BL
Neuralgia
/ metabolism
Spinal Cord
/ metabolism
Neuroinflammatory Diseases
/ metabolism
Sciatic Nerve
/ injuries
Disease Models, Animal
Glycoproteins
/ metabolism
Signal Transduction
NF-kappa B
/ metabolism
AdipoR1
CTRP9
Microglial polarization
Neuroinflammation
Neuropathic pain
Spinal cord
Journal
Cell biology and toxicology
ISSN: 1573-6822
Titre abrégé: Cell Biol Toxicol
Pays: Switzerland
ID NLM: 8506639
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
21
05
2024
accepted:
16
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
26
10
2024
Statut:
epublish
Résumé
Peripheral nerve injury triggers rapid microglial activation, promoting M1 polarization within the spinal cord, which exacerbates the progression of neuropathic pain. C1q/TNF-related protein 9 (CTRP9), an adiponectin homolog, is known to suppress macrophage activation and exhibit anti-inflammatory properties through the activation of adiponectin receptor 1 (AdipoR1) in various disease contexts. Nevertheless, the involvement of CTRP9 in microglial polarization in the context of neuropathic pain is still unclear. Our study aimed to how CTRP9 influences spinal microglial polarization, neuroinflammation, and pain hypersensitivity, as well as the underlying mechanism, using a neuropathic pain model in male mice with spared nerve injury (SNI) of sciatic nerve. Our findings revealed SNI elevated the spinal CTRP9 and AdipoR1 levels in microglia. Furthermore, intrathecal administration of recombinant CTRP9 (rCTRP9) substantially weakened mechanical hypersensitivity and heat-related pain response triggered by SNI. On the other hand, rCTRP9 mediated a phenotypic switch in microglia, from the pro-inflammatory M1 state to the anti-inflammatory M2 state, by influencing the spinal AMPK/NF-κB mechanism in SNI mice. Additionally, treatment with AdipoR1 siRNA or an AMPK-specific antagonist both reversed the effects of CTRP9 on the phenotypic switching of spinal microglia and pain hypersensitivity. Collectively, these results indicate that CTRP9 ameliorates mechanical hypersensitivity and heat-related pain response, shifted the balance of microglia towards the anti-inflammatory M2 state, and suppresses neuroinflammatory responses by modulating the AMPK/NF-κB pathway, mediated by AdipoR1 activation, in mice with SNI.
Identifiants
pubmed: 39460844
doi: 10.1007/s10565-024-09933-x
pii: 10.1007/s10565-024-09933-x
doi:
Substances chimiques
Receptors, Adiponectin
0
adiponectin receptor 1, mouse
0
Adiponectin
0
CTRP9 protein, mouse
0
Glycoproteins
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
91Subventions
Organisme : Natural Science Foundation of Hubei Province
ID : 2024AFB067
Informations de copyright
© 2024. The Author(s).
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