The anti-inflammatory and analgesic effects of intraperitoneal melatonin after spinal nerve ligation are mediated by inhibition of the NF-κB/NLRP3 inflammasome signaling pathway.
Brain Res Bull
; 169: 156-166, 2021 04.
Article
de En
| MEDLINE
| ID: mdl-33508403
ABSTRACT
OBJECTIVE:
To explore the potential analgesic effect of melatonin and its underlying molecular mechanisms in a neuropathic pain model induced by spinal nerve ligation (SNL).METHODS:
The experimental animals were divided into different groups including sham, vehicle, melatonin (MT) treatment, caspase-1 inhibitor (VX-765) treatment and MT2 antagonist (4P-PDOT) treatment. On the first three successive postoperative days, rats were intraperitoneally administered with MT, VX-765 or combination of MT and 4P-PDOT. Hyperalgesic behavior after SNL was evaluated using the paw withdrawal threshold (PWT). We then assessed expression of tumor necrosis factor-α (TNF-α), IL-18, interleukin-1ß (IL-1ß), NLRP3 inflammasome components, and nuclear factor-κB (NF-κB) activation using enzyme-linked immunosorbent assay kits (ELISA), real-time PCR, immunohistochemistry, and western blot, respectively, in spinal cord horn tissues extracted on postoperative day 7.RESULTS:
The results showed that melatonin treatment alleviated SNL-induced allodynia. We observed an SNL-induced upregulation of TNF-α, IL-18, IL-1ß, NLRP3, ASC, cleaved caspase-1, and NF-κB in the lumbar spinal cord horn of rats, which was significantly attenuated by intraperitoneal injection of melatonin or VX-765. Additionally, co-treatment of melatonin and 4P-PDOT abrogated the analgesic and anti-inflammatory effect of melatonin.CONCLUSION:
Melatonin had potent analgesic and anti-inflammatory effects in SNL-induced neuropathic pain via NF-κB/NLRP3 inflammasome signaling pathway. Our results therefore suggested that this pathway could represent a novel therapeutic target for the management of neuropathic pain.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Nerfs spinaux
/
Analgésiques
/
Mélatonine
/
Anti-inflammatoires
/
Névralgie
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Brain Res Bull
Année:
2021
Type de document:
Article
Pays d'affiliation:
Chine