Functional interplay between gelatinases and hyperalgesia in endotoxin-induced localized inflammatory pain

• Published in: Pain (Amsterdam) Vol. 84; no. 2-3; pp. 397 - 405
• Main Authors: Talhouk, R S, Hajjar, L, Abou-Gergi, R, Simaa'n, C J, Mouneimne, G, Saade', N E, Safieh-Garabedian, B
• Format: Journal Article
• Language: English
• Published: United States 01-02-2000
• Subjects: Animals; Endotoxins; Enzyme Inhibitors - pharmacology; Gelatinases - physiology; Hindlimb - enzymology; Hindlimb - physiopathology; Hot Temperature; Hyperalgesia - physiopathology; Inflammation - enzymology; Inflammation - physiopathology; Male; Metalloendopeptidases - antagonists & inhibitors; Mice; Mice, Inbred BALB C; Pain - enzymology; Pain - physiopathology; Physical Stimulation; Sodium Chloride; Thymic Factor, Circulating - pharmacology; Zinc - pharmacology
• ISSN: 0304-3959
• DOI: 10.1016/S0304-3959(99)00238-9

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.