Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice.
Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia. Without challenge, the heparanase overexpression did not significantly affect the mice in response to mechanical, cold and heat stimulation. Unilateral subcutaneous administration of carrageenan produced hypersensitivity to mechanical and cold in both wildtype and the heparanase overexpression (Hpa-tg) mice 24h after treatment. In comparison to wildtype animals, the Hpa-tg mice showed significantly reduced mechanical and cold hypersensitivity. This may, at least partially, due to the reduced mast cell infiltration at the site of inflammation in Hpa-tg mice. These data support a role for heparanase that reduces localized inflammation and inflammatory hyperalgesia in mice.
Department of Physiology and Pharmacology, Section of Integrative Pain Research, Karolinska Institutet, Stockholm, Sweden.
Lili
L
Li
Bo
B
Wang
Tianle
T
Gao
Xiao
X
Zhang
Jing-Xia
JX
Hao
Israel
I
Vlodavsky
Zsuzsanna
Z
Wiesenfeld-Hallin
Xiao-Jun
XJ
Xu
Jin-Ping
JP
Li
D000818:Animals; D002351:Carrageenan; D003080:Cold Temperature; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D059225:Nociception; D010812:Physical Stimulation; D000099175:Heparanase
D002351:Carrageenan; D005966:Glucuronidase; D000099175:Heparanase