PMID- 32939611
OWN - NLM
STAT- MEDLINE
DCOM- 20210713
LR  - 20210713
IS  - 1568-5608 (Electronic)
IS  - 0925-4692 (Linking)
VI  - 28
IP  - 6
DP  - 2020 Dec
TI  - Antinociception induced by artemisinin nanocapsule in a model of postoperative 
      pain via spinal TLR4 inhibition.
PG  - 1537-1551
LID - 10.1007/s10787-020-00756-w [doi]
AB  - 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), and Lipopolysaccharide 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-1beta) were 
      quantified by western blot and enzyme-linked immunosorbent assay, respectively. 
      The results showed that free ART reduced postoperative pain (P < 0.001, 
      F(5,30) = 7.49, 16.66% for 1000 ng dose; and P < 0.01, F(5,30) = 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(5,30) = 4.94; 43.75, 39.58 and 72.91% for the 250, 
      500 and 1000 ng doses, respectively) and 28th (P < 0.05; F(5,30) = 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-1beta 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-1beta.
FAU - Elisei, L M S
AU  - Elisei LMS
AD  - Sciences of Motricity Institute, Faculty of Motricity Sciences, Federal 
      University of Alfenas, Jovino Fernandes Sales Ave. 2600, Alfenas, 37133-840, 
      Brazil.
FAU - Moraes, T R
AU  - Moraes TR
AD  - Sciences of Motricity Institute, Faculty of Motricity Sciences, Federal 
      University of Alfenas, Jovino Fernandes Sales Ave. 2600, Alfenas, 37133-840, 
      Brazil.
FAU - Malta, I H
AU  - Malta IH
AD  - Sciences of Motricity Institute, Faculty of Motricity Sciences, Federal 
      University of Alfenas, Jovino Fernandes Sales Ave. 2600, Alfenas, 37133-840, 
      Brazil.
FAU - Charlie-Silva, I
AU  - Charlie-Silva I
AD  - Department of Pharmacology, University de Sao Paulo, Sao Paulo, Brazil.
FAU - Sousa, I M O
AU  - Sousa IMO
AD  - Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil.
FAU - Veras, F P
AU  - Veras FP
AD  - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao 
      Paulo, Ribeirao Preto, Brazil.
FAU - Foglio, M A
AU  - Foglio MA
AD  - Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil.
FAU - Fraceto, L F
AU  - Fraceto LF
AD  - Institute of Science and Technology, Sao Paulo State University, Sorocaba, 
      Brazil.
FAU - Galdino, G
AU  - Galdino G
AUID- ORCID: 0000-0002-1898-1973
AD  - Sciences of Motricity Institute, Faculty of Motricity Sciences, Federal 
      University of Alfenas, Jovino Fernandes Sales Ave. 2600, Alfenas, 37133-840, 
      Brazil. giovanegsouza@yahoo.com.br.
LA  - eng
GR  - 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - 2014/16008-3/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
PT  - Journal Article
DEP - 20200916
PL  - Switzerland
TA  - Inflammopharmacology
JT  - Inflammopharmacology
JID - 9112626
RN  - 0 (Analgesics)
RN  - 0 (Artemisinins)
RN  - 0 (Cytokines)
RN  - 0 (Nanocapsules)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Analgesics/*pharmacology
MH  - Animals
MH  - Artemisinins/*pharmacology
MH  - Cytokines/metabolism
MH  - Hyperalgesia/drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Microglia/drug effects/metabolism
MH  - Nanocapsules/*administration & dosage
MH  - Pain, Postoperative/*drug therapy/metabolism
MH  - Spinal Cord/*drug effects/metabolism
MH  - Toll-Like Receptor 4/*antagonists & inhibitors
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Artemisinin
OT  - Postoperative pain
OT  - Proinflammatory cytokines
OT  - Spinal cord
OT  - Toll-like receptor 4
EDAT- 2020/09/18 06:00
MHDA- 2021/07/14 06:00
CRDT- 2020/09/17 05:46
PHST- 2020/05/07 00:00 [received]
PHST- 2020/09/05 00:00 [accepted]
PHST- 2020/09/18 06:00 [pubmed]
PHST- 2021/07/14 06:00 [medline]
PHST- 2020/09/17 05:46 [entrez]
AID - 10.1007/s10787-020-00756-w [pii]
AID - 10.1007/s10787-020-00756-w [doi]
PST - ppublish
SO  - Inflammopharmacology. 2020 Dec;28(6):1537-1551. doi: 10.1007/s10787-020-00756-w. 
      Epub 2020 Sep 16.