Background & Aims
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis, pain, and progressive joint damage. The pathogenesis of RA mainly involves oxidative stress which is responsible for inflammation and pain. Gabexate mesylate, a serine protease inhibitor with anti-inflammatory properties helps in managing RA pain by suppressing NF-?? and nitric oxide pathway.
Methods
Animals-Male S D rats (wt-200-220 gm)
Drugs-Gabexate Mesilate (Dose:10mg/kg,20mg/kg,40mg/kg), Indomethacin(5mg/kg)
Animal Model: CFA-induced arthritis
Behavior essays
•Von-Frey test: Mechanical allodynia
•Pin-prick test: Mechanical Hyperalgesia
•Hargreaves test: Thermal Hyperalgesia
•Acetone Drop test: Cold allodynia
•Ice-floor test: Cold Hyperalgesia
•CNS toxicity: Rotarod test, open field test
Biochemical tests-GSH, nitrite, LPO
Results
1.Gabexate mesylate attenuates mechanical allodynia in CFA-induced arthritis rats.
2.Gabexate mesylate decreases heat hyperalgesia in CFA-induced arthritis rats.
3.Gabexate mesylate decreases cold allodynia in CFA-induced arthritis rats.
4.Gabexate mesylate restores paw thickness in CFA-induced arthritis rats.
5.Gabexate mesylate restores body weight in CFA-induced arthritis rats.
6.Gabexate mesylate did not affect locomotor or exploratory activity as well as did not observe a significant change in motor incoordination in the Rota-rod test.
Conclusions
Gabexate mesylate prevents proteolytic destruction of I?? resulting in suppression of the NF?B signaling pathway and downregulates the activation of TRPV1 signaling in the spinal dorsal horn neuron. This leads to a decrease in the production of inflammatory cytokines and also prevents spontaneous ongoing pain. The current study revealed that gabexate mesylate could be a better and safer therapeutics for treating rheumatoid arthritis pain and inflammation.
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Presenting Author
Km Nivedita Verma
Poster Authors
Nivedita Verma
OTHR
DEPARTMENT OF PHARMACEUTICAL ENGINEERING AND TECHNOLOGY IIT BHU VARANASI
Lead Author
Topics
- Pain Imaging