Functional interplay between gelatinases and hyperalgesia in endotoxin-induced localized inflammatory pain.
The role of ECM-degrading proteinases in normal developmental processes and in pathological conditions is extensively studied. However, few reports describe the role ECM-degrading proteinases play in modulating hyperalgesia. The goal of this study is to describe the regulation of gelatinases during endotoxin mediated local inflammation, induced by intra plantar endotoxin (ET; 1.25 microg/50 microl) injection in Balb/c mice, and to correlate that with hyperalgesia. ET injections induced hyperalgesia, as determined by hot plate and paw pressure tests, which peaked by 24 h and recovered by 48 h post-injection. Contralateral paw of ET injected mice and saline injected paws in control mice elicited no hyperalgesia. Zymography showed that ET and saline injected paws elicited increased gelatinase activity by 9 h after injection. However, only the former maintained high levels of expression of a 90 kD gelatinase up to at least 96 h post ET injection, while in the latter gelatinase expression was down regulated by 24 h. Interestingly, the 90-kD gelatinase was upregulated in the contralateral paw of the ET-injected mice beyond 48 h post injection. Saline injection in that paw, during a time when gelatinases are upregulated, induced hyperalgesia. Intraperitoneal injection of either ZnCl(2) (100 microM), thymulin (5 microg/100 microl), or morphine (2 mg/kg/100 microl) reversed the ET-induced hyperalgesia and suppressed gelatinase activity. Furthermore, intraperitoneal injection of MPI, an ECM-degrading proteinase inhibitor, reversed ET induced hyperalgesia. Taken together, the above suggests that a functional interplay exists between gelatinase upregulation triggered by ET injections and hyperalgesia. The exact mechanism underlying such correlation remains to be determined.
Talhouk
R S
RS
Department of Biology, P.O. Box 11-0236 American University of Beirut, Beirut, Lebanon.
Hajjar
L
L
Abou-Gergi
R
R
Simaa'n
C J
CJ
Mouneimne
G
G
Saade'
N E
NE
Safieh-Garabedian
B
B
D000818:Animals; D004731:Endotoxins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018093:Gelatinases / Q000502:physiology*; D006614:Hindlimb / Q000201:enzymology / Q000503:physiopathology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000201:enzymology / Q000503:physiopathology*; D010812:Physical Stimulation; D012965:Sodium Chloride; D013935:Thymic Factor, Circulating / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D004731:Endotoxins; D004791:Enzyme Inhibitors; D012965:Sodium Chloride; D013935:Thymic Factor, Circulating; D018093:Gelatinases; D008666:Metalloendopeptidases; D015032:Zinc