Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and inflammatory pain responses in the rat

Sungjae Yoo, Shanshu Han, Young Shin Park, Jang Hern Lee, Uhtaek Oh, Sun Wook Hwang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

Original languageEnglish
Pages (from-to)417-422
Number of pages6
JournalMolecules and Cells
Volume27
Issue number4
DOIs
Publication statusPublished - 2009 May 12

Fingerprint

Lipoxygenase Inhibitors
Lipoxygenase
Carrageenan
Pain
Hot Temperature
Cell Count
Proto-Oncogene Proteins c-fos
Inflammation
Nociception
Spinal Cord
Hypersensitivity
Injections

Keywords

  • Fos immunohystochemistry
  • Inflammation
  • Lipoxygenase
  • Pain
  • TRPV1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and inflammatory pain responses in the rat. / Yoo, Sungjae; Han, Shanshu; Park, Young Shin; Lee, Jang Hern; Oh, Uhtaek; Hwang, Sun Wook.

In: Molecules and Cells, Vol. 27, No. 4, 12.05.2009, p. 417-422.

Research output: Contribution to journalArticle

Yoo, Sungjae ; Han, Shanshu ; Park, Young Shin ; Lee, Jang Hern ; Oh, Uhtaek ; Hwang, Sun Wook. / Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and inflammatory pain responses in the rat. In: Molecules and Cells. 2009 ; Vol. 27, No. 4. pp. 417-422.
@article{7d0384eedcf549ae8c2276c76226a6c0,
title = "Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and inflammatory pain responses in the rat",
abstract = "Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.",
keywords = "Fos immunohystochemistry, Inflammation, Lipoxygenase, Pain, TRPV1",
author = "Sungjae Yoo and Shanshu Han and Park, {Young Shin} and Lee, {Jang Hern} and Uhtaek Oh and Hwang, {Sun Wook}",
year = "2009",
month = "5",
day = "12",
doi = "10.1007/s10059-009-0059-2",
language = "English",
volume = "27",
pages = "417--422",
journal = "Molecules and Cells",
issn = "1016-8478",
publisher = "Korean Society for Molecular and Cellular Biology",
number = "4",

}

TY - JOUR

T1 - Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and inflammatory pain responses in the rat

AU - Yoo, Sungjae

AU - Han, Shanshu

AU - Park, Young Shin

AU - Lee, Jang Hern

AU - Oh, Uhtaek

AU - Hwang, Sun Wook

PY - 2009/5/12

Y1 - 2009/5/12

N2 - Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

AB - Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

KW - Fos immunohystochemistry

KW - Inflammation

KW - Lipoxygenase

KW - Pain

KW - TRPV1

UR - http://www.scopus.com/inward/record.url?scp=65149102414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65149102414&partnerID=8YFLogxK

U2 - 10.1007/s10059-009-0059-2

DO - 10.1007/s10059-009-0059-2

M3 - Article

VL - 27

SP - 417

EP - 422

JO - Molecules and Cells

JF - Molecules and Cells

SN - 1016-8478

IS - 4

ER -