Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition

Detalhes bibliográficos
Autor(a) principal: Elisei, L. M. S.
Data de Publicação: 2020
Outros Autores: 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.
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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spelling 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
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