Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

ABSTRACT

Background@#This study examined the effects of gabexate mesilate on spinal nerve ligation (SNL)-induced neuropathic pain. To confirm the involvement of gabexate mesilate on neuroinflammation, we focused on the activation of nuclear factor-κB (NF-κB) and consequent the expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS). @*Methods@#Male Sprague-Dawley rats were used for the study. After randomization into three groups the sham-operation group, vehicle-treated group (administered normal saline as a control), and the gabexate group (administered gabexate mesilate 20 mg/kg), SNL was performed. At the 3rd day, mechanical allodynia was confirmed using von Frey filaments, and drugs were administered intraperitoneally daily according to the group. The paw withdrawal threshold (PWT) was examined on the 3rd, 7th, and 14th day. The expressions of p65 subunit of NF-κB, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and iNOS were evaluated on the 7th and 14th day following SNL. @*Results@#The PWT was significantly higher in the gabexate group compared with the vehicle-treated group (p < 0.05). The expressions of p65, proinflammatory cyto kines, and iNOS significantly decreased in the gabexate group compared with the vehicle-treated group (p < 0.05) on the 7th day. On the 14th day, the expressions of p65 and iNOS showed lower levels, but those of the proinflammatory cytokines showed no significant differences. @*Conclusions@#Gabexate mesilate increased PWT after SNL and attenuate the pro gress of mechanical allodynia. These results seem to be involved with the antiinflammatory effect of gabexate mesilate via inhibition of NF-κB, proinflammatory cytokines, and nitric oxide.