COX-2 expression and function in the hyperalgesic response to paw inflammation in mice.
Peripheral inflammation and edema are often accompanied by primary and secondary hyperalgesia which are mediated by both peripheral and central mechanisms. The role of cyclooxygenase-2 (COX-2)-mediated prostanoid production in hyperalgesia is a topic of substantial current interest. We have established a murine foot-pad inflammation model in which both pharmacologic and genetic tools can be used to characterize the role of COX-2 in hyperalgesia. Zymosan, an extract from yeast, injected into the plantar surface of the hindpaw induces an edema response and an increase in COX-2 expression in the hindpaw, spinal cord and brain. Zymosan-induced primary hyperalgesia, measured as a decrease in hindpaw withdrawal latency in response to a thermal stimulus, is long-lasting and is not inhibited by pre-treatment with the systemic COX-2 selective inhibitor, parecoxib (20 mg/kg). In contrast, the central component of hyperalgesia, measured as a reduction in tail flick latency in response to heat, is reduced by parecoxib. Zymosan-induced primary hyperalgesia in Cox-2-/- mice is similar to that of their Cox-2+/+ littermate controls. However, the central component of hyperalgesia is substantially reduced in Cox-2-/- versus Cox-2+/+ mice, and returns to baseline values much more rapidly. Thus pharmacological data suggest, and genetic experiments confirm, (i) that primary hyperalgesia in response to zymosan inflammation in the mouse paw is not mediated by COX-2 function and (ii) that COX-2 function plays a major role in the central component of hyperalgesia in this model of inflammation.
Jain
Naveen K
NK
Department of Biological Chemistry, UCLA School of Medicine, 341 Boyer Hall, University of California, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
Ishikawa
Tomo-o
TO
Spigelman
Igor
I
Herschman
Harvey R
HR
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015054:Zymosan
D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D015054:Zymosan; C409945:parecoxib; D051546:Cyclooxygenase 2