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Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines
BACKGROUND: The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558391/ https://www.ncbi.nlm.nih.gov/pubmed/23268791 http://dx.doi.org/10.1186/1742-2094-9-278 |
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author | Hu, Shan Mao-Ying, Qi-Liang Wang, Jun Wang, Zhi-Fu Mi, Wen-Li Wang, Xiao-Wei Jiang, Jian-Wei Huang, Ya-Lin Wu, Gen-Cheng Wang, Yan-Qing |
author_facet | Hu, Shan Mao-Ying, Qi-Liang Wang, Jun Wang, Zhi-Fu Mi, Wen-Li Wang, Xiao-Wei Jiang, Jian-Wei Huang, Ya-Lin Wu, Gen-Cheng Wang, Yan-Qing |
author_sort | Hu, Shan |
collection | PubMed |
description | BACKGROUND: The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. METHODS: The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t.) or intravenous (i.v.) injection. The protein level of LXA4 receptor (ALX) was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. RESULTS: Our results demonstrated that: 1) i.t. injection with the same dose (0.3 nmol) of lipoxin A4 (LXA4), lipoxin B4 (LXB4) or aspirin-triggered-15-epi-lipoxin A4 (ATL) could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2) The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3) Immunohistochemistry showed that the lipoxin receptor (ALX)-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4) Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly attenuate the expression of the mRNA of proinflammatory cytokines (IL-1β and TNF-α) in the spinal cord in CIBP. CONCLUSIONS: Taken together, the results of our study suggest that LXs and analogues exert strong analgesic effects on CIBP. These analgesic effects in CIBP are associated with suppressing the expression of spinal proinflammatory cytokines. |
format | Online Article Text |
id | pubmed-3558391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35583912013-01-31 Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines Hu, Shan Mao-Ying, Qi-Liang Wang, Jun Wang, Zhi-Fu Mi, Wen-Li Wang, Xiao-Wei Jiang, Jian-Wei Huang, Ya-Lin Wu, Gen-Cheng Wang, Yan-Qing J Neuroinflammation Research BACKGROUND: The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. METHODS: The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t.) or intravenous (i.v.) injection. The protein level of LXA4 receptor (ALX) was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. RESULTS: Our results demonstrated that: 1) i.t. injection with the same dose (0.3 nmol) of lipoxin A4 (LXA4), lipoxin B4 (LXB4) or aspirin-triggered-15-epi-lipoxin A4 (ATL) could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2) The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3) Immunohistochemistry showed that the lipoxin receptor (ALX)-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4) Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly attenuate the expression of the mRNA of proinflammatory cytokines (IL-1β and TNF-α) in the spinal cord in CIBP. CONCLUSIONS: Taken together, the results of our study suggest that LXs and analogues exert strong analgesic effects on CIBP. These analgesic effects in CIBP are associated with suppressing the expression of spinal proinflammatory cytokines. BioMed Central 2012-12-26 /pmc/articles/PMC3558391/ /pubmed/23268791 http://dx.doi.org/10.1186/1742-2094-9-278 Text en Copyright ©2012 Hu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Hu, Shan Mao-Ying, Qi-Liang Wang, Jun Wang, Zhi-Fu Mi, Wen-Li Wang, Xiao-Wei Jiang, Jian-Wei Huang, Ya-Lin Wu, Gen-Cheng Wang, Yan-Qing Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
title | Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
title_full | Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
title_fullStr | Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
title_full_unstemmed | Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
title_short | Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
title_sort | lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558391/ https://www.ncbi.nlm.nih.gov/pubmed/23268791 http://dx.doi.org/10.1186/1742-2094-9-278 |
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