1. Academic Validation
  2. 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

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. 2021 Apr;169:156-166. doi: 10.1016/j.brainresbull.2021.01.015.
Yi-Hao Wang 1 Yu-Ru Tang 2 Xiao Gao 2 Juan Liu 3 Nan-Nan Zhang 4 Zhao-Jun Liang 5 Yan Li 6 Li-Xiao Pan 7
Affiliations

Affiliations

  • 1 Department of Pain Management, Qingdao Municipal Hospital, Shandong Province, 266011, China.
  • 2 Qingdao Mental Health Center, Qingdao University, Shandong Province, 266034, China.
  • 3 Department of Anesthesiology, Maternity and Child Hospital of Shandong Province, Shandong Province, 250014, China.
  • 4 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Shandong Province, 266003, China.
  • 5 Department of Anesthesiology, Qingdao Municipal Hospital, Shandong Province, 266011, China.
  • 6 Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Shandong Province, 266003, China.
  • 7 Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Shandong Province, 266003, China. Electronic address: [email protected].
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-1β (IL-1β), 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-1β, 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.

Keywords

Caspase-1 inhibitor; Melatonin; NF-κB; NLRP3 inflammasome; Neuropathic pain.

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