The involvement of spinal annexin A10/NF-κB/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 mecha...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | BMC Neuroscience |
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| Online Access: | http://link.springer.com/article/10.1186/s12868-019-0513-9 |
| _version_ | 1818292625640259584 |
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| author | LiHong Sun Qi Xu WenXin Zhang CuiCui Jiao Hui Wu XinZhong Chen |
| author_facet | LiHong Sun Qi Xu WenXin Zhang CuiCui Jiao Hui Wu XinZhong Chen |
| author_sort | LiHong Sun |
| collection | DOAJ |
| description | 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-κB), and maisrix metalloproteinase-9 (MMP-9) in the spinal cord. The levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukine-1β (IL-1β), and interleukine-6 (IL-6), were explored by ELISA kits. The effects of both knockdown of spinal ANXA10 and inhibition of NF-κB 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-κB, TNF-α, IL-1β, 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-κB, TNF-α and IL-1β 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-κB/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-κB pathway in the development rather than the maintenance of NP. |
| first_indexed | 2024-12-13T03:02:56Z |
| format | Article |
| id | doaj.art-4913896714564be3a2f3ad07ffeaeb62 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-13T03:02:56Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-4913896714564be3a2f3ad07ffeaeb622022-12-22T00:01:47ZengBMCBMC Neuroscience1471-22022019-06-012011910.1186/s12868-019-0513-9The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in ratsLiHong Sun0Qi Xu1WenXin Zhang2CuiCui Jiao3Hui Wu4XinZhong Chen5Department of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang UniversityAbstract 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-κB), and maisrix metalloproteinase-9 (MMP-9) in the spinal cord. The levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukine-1β (IL-1β), and interleukine-6 (IL-6), were explored by ELISA kits. The effects of both knockdown of spinal ANXA10 and inhibition of NF-κB 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-κB, TNF-α, IL-1β, 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-κB, TNF-α and IL-1β 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-κB/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-κB pathway in the development rather than the maintenance of NP.http://link.springer.com/article/10.1186/s12868-019-0513-9PainANXA10NF-κBMMP-9Spinal cordCytokines |
| spellingShingle | LiHong Sun Qi Xu WenXin Zhang CuiCui Jiao Hui Wu XinZhong Chen The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats BMC Neuroscience Pain ANXA10 NF-κB MMP-9 Spinal cord Cytokines |
| title | The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats |
| title_full | The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats |
| title_fullStr | The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats |
| title_full_unstemmed | The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats |
| title_short | The involvement of spinal annexin A10/NF-κB/MMP-9 pathway in the development of neuropathic pain in rats |
| title_sort | involvement of spinal annexin a10 nf κb mmp 9 pathway in the development of neuropathic pain in rats |
| topic | Pain ANXA10 NF-κB MMP-9 Spinal cord Cytokines |
| url | http://link.springer.com/article/10.1186/s12868-019-0513-9 |
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