Dataset Information

The involvement of spinal annexin A10/NF-?B/MMP-9 pathway in the development of neuropathic pain in rats.

ABSTRACT: BACKGROUND:Neuropathic pain (NP) is a prevalent disease, which badly impairs the life quality of patients. The underlying mechanism of NP is still not fully understood. It has been reported that spinal Annexin A10 (ANXA10) contributes to NP. This study aims at exploring the underlying mechanisms of spinal ANXA10 in regulating NP in rats. METHODS:Spinal nerve ligation (SNL) was adopted to establish a NP model in rats. After SNL, paw withdrawal threshold and paw withdrawal latency were recorded to measure pain behaviors, RT-PCR was used to check the change of the expression of spinal ANXA10 mRNA, western blot analysis was used to detect the change of the protein level of ANXA10, nuclear factor kappa B (NF-?B), and maisrix metalloproteinase-9 (MMP-9) in the spinal cord. The levels of proinflammatory cytokines, including tumor necrosis factor-? (TNF-?), interleukine-1? (IL-1?), and interleukine-6 (IL-6), were explored by ELISA kits. The effects of both knockdown of spinal ANXA10 and inhibition of NF-?B on pain behaviors and the expression of MMP-9 and proinflammatory cytokines were investigated. RESULTS:Our present findings highlighted that SNL caused pain hypersensitivity and increased the expression of spinal ANXA10/pNF-?B, TNF-?, IL-1?, and IL-6 both in the early and late phase of NP in rats, while spinal MMP-9 was only slightly increased in the early phase of NP. Knockdown of ANXA10 at the spinal cord level suppressed the SNL-induced hyperalgesia and blocked the activation of NF-?B, TNF-? and IL-1? both in the early and late phase of NP. Spinal ANXA10 knockdown could prevent the upregulation of spinal MMP-9 in the early phase and inhibit IL-6 expression in the late phase of SNL-induced NP. CONCLUSIONS:In conclusion, spinal ANXA10/NF-?B/MMP-9 pathway, along with the activation of proinflammatory cytokines, was involved in the SNL-induced NP. MMP-9 may act as the downstream target of ANXA10/NF-?B pathway in the development rather than the maintenance of NP.

SUBMITTER: Sun L

PROVIDER: S-EPMC6580616 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats.

Sun LiHong L Xu Qi Q Zhang WenXin W Jiao CuiCui C Wu Hui H Chen XinZhong X

BMC neuroscience 20190617 1

<h4>Background</h4>Neuropathic pain (NP) is a prevalent disease, which badly impairs the life quality of patients. The underlying mechanism of NP is still not fully understood. It has been reported that spinal Annexin A10 (ANXA10) contributes to NP. This study aims at exploring the underlying mechanisms of spinal ANXA10 in regulating NP in rats.<h4>Methods</h4>Spinal nerve ligation (SNL) was adopted to establish a NP model in rats. After SNL, paw withdrawal threshold and paw withdrawal latency w ...[more]

PMID: 31208343

Similar Datasets

Project description:BackgroundThe participation of spinal P2X receptors in neuropathic pain is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participation of spinal microglia and astrocytes in the pronociceptive role of P2Y6,11 receptors.ResultsSpinal administration of the selective P2Y6 (MRS2578, 10-100 μM) and P2Y11 (NF340, 0.3-30 μM) receptor antagonists reduced tactile allodynia in spinal nerve ligated rats. Nerve injury increased the expression of P2Y6,11 receptors at 7, 14 and 21 days after injury. Furthermore, intrathecal administration of MRS2578 (100 μM/day) and NF340 (30 μM/day) for 3 days significantly reduced spinal nerve injury-induced increase in P2Y6,11 receptors expression, respectively. Spinal treatment (on day 14 after injury) with minocycline (100 μg/day) or fluorocitrate (1 nmol/day) for 7 days reduced tactile allodynia and spinal nerve injury-induced up-regulation in Iba-1 and GFAP, respectively. In addition, minocycline reduced nerve injury-induced up-regulation in P2Y6,11 receptors whereas that fluorocitrate diminished P2Y11, but not P2Y6, receptors up-regulation. Intrathecal treatment (on day 21 after injury) with the selective P2Y6 (PSB0474, 3-30 μM) and P2Y11 (NF546, 1-10 μM) receptor agonists produced remarkable tactile allodynia in nerve ligated rats previously treated with minocycline or fluorocitrate for 7 days.ConclusionsOur data suggest that spinal P2Y6 is present in spinal microglia while P2Y11 receptors are present in both spinal microglia and astrocytes, and both receptors are up-regulated in rats subjected to spinal nerve injury. In addition, our data suggest that the spinal P2Y6 and P2Y11 receptors participate in the maintenance of neuropathic pain.

Project description:Study designExperimental study of the role and mechanism of spinal NFκB-CXCL1/CXCR2 in rats with nucleus pulposus-induced radicular pain.ObjectiveThis study investigated the role and mechanism of spinal NFκB-CXCL1/CXCR2 in autologous nucleus pulposus-induced pain behavior in rats and to clarify the involvement and regulation of spinal NFκB as an upstream molecule of CXCL1 in autologous nucleus pulposus-induced radicular pain in rats.Summary of background dataThe inflammatory response of nerve roots is an important mechanism for the occurrence of chronic pain. NFκB-CXCL1/CXCR2 pathway plays an important role in the development of radicular pain, but its regulatory mechanism in the model of radicular pain induced by autologous nucleus pulposus is still unclear.Materials and methodsWe established a rat model of autologous medullary nucleus transplantation. We observed and recorded the changes in 50% mechanical withdrawal threshold and thermal withdrawal latency before and after the administration of CXCL1-neutralizing antibodies, CXCR2 inhibitor, and NFκB inhibitor in each group of rats and evaluated the expression of NFκB, CXCL1, and CXCR2 in the spinal dorsal horn using immunofluorescence and Western blot. To compare differences between groups in behavioral testing, analysis of variance was employed. Dunnett's method was used to compare differences at different time points within a group and between different groups at the same time point. A comparison of the relative concentration of protein, relative concentration of mRNA, and semiquantitative data from immunofluorescence staining was conducted utilizing one-way ANOVA and Dunnett's pairwise comparison.ResultsAutologous nucleus pulposus transplantation can induce radicular pain in rats and upregulate the expression of CXCL1, CXCR2, and NFκB in the spinal cord. CXCL1 is co-expressed with astrocytes, CXCR2 with neurons, and NFκB with both astrocytes and neurons. The application of CXCL1 neutralizing antibodies, CXCR2 inhibitors, and NFκB inhibitors can alleviate pain hypersensitivity induced by autologous nucleus pulposus transplantation in rats. Inhibitors of NFκB could downregulate the expression of CXCL1 and CXCR2.ConclusionsWe found that spinal NFκB is involved in NP-induced radicular pain in rats through the activation of CXCL1/CXCR2, enriching the mechanism of medullary-derived radicular pain and providing a possible new target and theoretical basis for the development of more effective anti-inflammatory and analgesic drugs for patients with chronic pain following LDH.

Dataset Information

The involvement of spinal annexin A10/NF-?B/MMP-9 pathway in the development of neuropathic pain in rats.

Publications

The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets