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Authors Zhang AL, Wang K, Ding LH, Bao XN, Wang X, Qiu XB, Liu JB
Received 15 August 2016
Accepted for publication 2 December 2016
Published 13 February 2017 Volume 2017:10 Pages 375—382
DOI https://doi.org/10.2147/JPR.S119820
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Enrica Santarcangelo
Abstract: Lumbar disc herniation (LDH) is an important cause of radiculopathy, but
the underlying mechanisms are incompletely understood. Many studies suggested
that local inflammation, rather than mechanical compression, results in
radiculopathy induced by LDH. On the molecular and cellular level, nuclear
factor-kappa B (NF-κB) and nucleotide-binding domain-like receptor protein 3
(NLRP3) inflammasome have been implicated in the regulation of
neuroinflammation formation and progression. In this study, the autologous
nucleus pulposus (NP) was implanted in the left L5 dorsal root ganglion (DRG)
to mimic LDH in rats. We investigated the expression of NF-κB and the
components of NLRP3 inflammasome in the DRG neurons in rats. Western blotting
and immunofluorescence for the related molecules, including NLRP3,
apoptosis-associated speck-like protein containing caspase-1 activator domain
(ASC), caspase-1, interleukin (IL)-1β, IL-18, IκBα, p-IκBα, p65, p-p65, and
calcitonin gene-related peptide (CGRP) were examined. In the NP-treated group,
the activations of NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 in
DRG neurons in rats were elevated at 1 day after surgery, and the peak occurred
at 7 days. Treatment with Bay11-7082, an inhibitor of the actions of IKK-β, was
able to inhibit expression and activation of the molecules (NLRP3, ASC,
caspase-1, IL-1β, IL-18, p-IκBα, and p-p65) and relieve the pain in rats. Our
study shows that NF-κB and NLRP3 inflammasome are involved in the maintenance
of NP-induced pain, and that Bay11-7082 could alleviate mechanical allodynia
and thermal hyperalgesia by inhibiting NF-κB and NLRP3 inflammasome activation.
Keywords: pain, NLRP3, NF-κB, dorsal root
ganglion, nucleus pulposus