title: Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation.
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.
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Ailiang
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Lianghua
authors.initials: L
authors.lastname: Ding
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Xinnan
authors.initials: X
authors.lastname: Bao
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Xubin
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
keywords: NF-κB; NLRP3; dorsal root ganglion; nucleus pulposus; pain