Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1007/s10787-020-00756-w http://hdl.handle.net/11449/210454 |
Resumo: | Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), andLipopolysaccharide Rhodobacter sphaeroides(LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), and interleukin-1-beta (IL-1 beta) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001,F-5,F-30 = 7.49, 16.66% for 1000 ng dose; andP < 0.01,F-5,F-30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001;F-5,F-30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05;F-5,F-30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-alpha, and IL-1 beta induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-alpha and IL-1 beta. |
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Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibitionArtemisininPostoperative painSpinal cordToll-like receptor 4Proinflammatory cytokinesArtemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), andLipopolysaccharide Rhodobacter sphaeroides(LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), and interleukin-1-beta (IL-1 beta) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001,F-5,F-30 = 7.49, 16.66% for 1000 ng dose; andP < 0.01,F-5,F-30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001;F-5,F-30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05;F-5,F-30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-alpha, and IL-1 beta induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-alpha and IL-1 beta.Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Alfenas, Fac Motr Sci, Sci Motr Inst, Jovino Fernandes Sales Ave 2600, BR-37133840 Alfenas, BrazilUniv Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Estadual Campinas, Fac Pharmaceut Sci, Campinas, BrazilSao Paulo State Univ, Inst Sci & Technol, Sorocaba, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, BrazilSao Paulo State Univ, Inst Sci & Technol, Sorocaba, BrazilCAPES: 001FAPESP: 2014/16008-3SpringerUniv Fed AlfenasUniversidade de São Paulo (USP)Universidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Elisei, L. M. S.Moraes, T. R.Malta, I. H.Charlie-Silva, I.Sousa, I. M. O.Veras, F. P.Foglio, M. A.Fraceto, L. F. [UNESP]Galdino, G.2021-06-25T15:38:43Z2021-06-25T15:38:43Z2020-09-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1537-1551http://dx.doi.org/10.1007/s10787-020-00756-wInflammopharmacology. Basel: Springer Basel Ag, v. 28, n. 6, p. 1537-1551, 2020.0925-4692http://hdl.handle.net/11449/21045410.1007/s10787-020-00756-wWOS:000570059600001Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInflammopharmacologyinfo:eu-repo/semantics/openAccess2021-10-23T20:17:34Zoai:repositorio.unesp.br:11449/210454Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:22:33.991223Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
title |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
spellingShingle |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition Elisei, L. M. S. Artemisinin Postoperative pain Spinal cord Toll-like receptor 4 Proinflammatory cytokines |
title_short |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
title_full |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
title_fullStr |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
title_full_unstemmed |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
title_sort |
Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition |
author |
Elisei, L. M. S. |
author_facet |
Elisei, L. M. S. Moraes, T. R. Malta, I. H. Charlie-Silva, I. Sousa, I. M. O. Veras, F. P. Foglio, M. A. Fraceto, L. F. [UNESP] Galdino, G. |
author_role |
author |
author2 |
Moraes, T. R. Malta, I. H. Charlie-Silva, I. Sousa, I. M. O. Veras, F. P. Foglio, M. A. Fraceto, L. F. [UNESP] Galdino, G. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Fed Alfenas Universidade de São Paulo (USP) Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Elisei, L. M. S. Moraes, T. R. Malta, I. H. Charlie-Silva, I. Sousa, I. M. O. Veras, F. P. Foglio, M. A. Fraceto, L. F. [UNESP] Galdino, G. |
dc.subject.por.fl_str_mv |
Artemisinin Postoperative pain Spinal cord Toll-like receptor 4 Proinflammatory cytokines |
topic |
Artemisinin Postoperative pain Spinal cord Toll-like receptor 4 Proinflammatory cytokines |
description |
Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), andLipopolysaccharide Rhodobacter sphaeroides(LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), and interleukin-1-beta (IL-1 beta) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001,F-5,F-30 = 7.49, 16.66% for 1000 ng dose; andP < 0.01,F-5,F-30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001;F-5,F-30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05;F-5,F-30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-alpha, and IL-1 beta induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-alpha and IL-1 beta. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-09-16 2021-06-25T15:38:43Z 2021-06-25T15:38:43Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1007/s10787-020-00756-w Inflammopharmacology. Basel: Springer Basel Ag, v. 28, n. 6, p. 1537-1551, 2020. 0925-4692 http://hdl.handle.net/11449/210454 10.1007/s10787-020-00756-w WOS:000570059600001 |
url |
http://dx.doi.org/10.1007/s10787-020-00756-w http://hdl.handle.net/11449/210454 |
identifier_str_mv |
Inflammopharmacology. Basel: Springer Basel Ag, v. 28, n. 6, p. 1537-1551, 2020. 0925-4692 10.1007/s10787-020-00756-w WOS:000570059600001 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Inflammopharmacology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1537-1551 |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129060234067968 |