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

Autor(es)

Elisei, L. M. S. ^[1] ; Moraes, T. R. ^[1] ; Malta, I. H. ^[1] ; Charlie-Silva, I. ^[2] ; Sousa, I. M. O. ^[3] ; Veras, F. P. ^[4] ; Foglio, M. A. ^[3] ; Fraceto, L. F. ^[5] ; Galdino, G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Alfenas, Fac Motr Sci, Sci Motr Inst, Jovino Fernandes Sales Ave 2600, BR-37133840 Alfenas - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[5] Sao Paulo State Univ, Inst Sci & Technol, Sorocaba - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INFLAMMOPHARMACOLOGY; v. 28, n. 6, p. 1537-1551, DEC 2020.
• Citações Web of Science: 0

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. (AU)

• Processo FAPESP: 14/16008-3 - Desenvolvimento de patches contendo a associação de artemeter - lumefantrina para o tratamento da malária causada por Plasmodium falciparum
• Beneficiário: Fabiana Volpe Zanutto
• Modalidade de apoio: Bolsas no Brasil - Doutorado