Analgesic and Antiallodynic Effects of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide in a Murine Model of Pain

Abstract

Introduction: Physical, chemical, thermal injuries along with infectious diseases lead to acute pain with associated inflammation, being the primary cause of hospital visits. Moreover, neuropathic pain associated with diabetes is a serious chronic disease leading to high morbidity and poor quality of life.

Objective: Earlier multiple sulphonamides have been reported to have an antinociceptive and antiallodynic profile. 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS), a synthetic sulfonamide with reported carbonic anhydrase inhibitory activity, was investigated for its potential effects in mice model of acute and diabetic neuropathic pain.

Methods and results: 4-FBS was given orally (p.o.) one hour before the test and then mice were screened for antinociceptive activity by using the tail immersion test, which showed significant antinociceptive effect at both 20 and 40 mg/kg doses. To explore the possible mechanisms, thermal analgesia of 4-FBS was reversed by the 5HT₃ antagonist ondansetron 1mg/kg intraperitoneally (i.p.) and by the µ receptor antagonist naloxone (1 mg/kg i.p.), implying possible involvement of serotonergic and opioidergic pathways in the analgesic effect of 4-FBS. Diabetes was induced in mice by a single dose of streptozotocin (STZ) 200 mg/kg i.p. After two weeks, animals first became hyperalgesic and progressively allodynic in the fourth week, which was evaluated through behavioral parameters like thermal and mechanical tests. 4-FBS at 20 and 40 mg/kg p.o. significantly reversed diabetes-induced hyperalgesia and allodynia at 30, 60, 90, and 120 minutes.

Conclusion: These findings are significant and promising while further studies are warranted to explore the exact molecular mechanism and the potential of 4-FBS in diabetic neuropathic pain.

Keywords: antinociception; diabetes mellitus; DM; neuropathic pain; streptozotocin; STZ; sulfonamides; von Frey filaments.

Figure 1

Effect of 4-FBS 20 mg/kg on tail flick latency time at different time-points. BALB/c mice (n=6/group) were used. The graph shows antinociceptive activity of 4-FBS 20 mg/kg p.o. in the tail-flick latency time. One way ANOVA followed by Dunnett’s test shows significance difference between at 30, 60, 90 and 120 min between 4-FBS vs. saline vehicle control, *p<0.05, **p<0.01, ***p<0.001.

Figure 2

Effect of 4-FBS 20 mg/kg on tail flick latency time at different time-points. BALB/c mice (n=6/group) were used. The graph shows the antinociceptive activity of 4-FBS 40 mg/kg p.o. in tail-flick latency time. One way ANOVA followed by Dunnett’s test shows significance difference at 30, 60 and 90 except 120 min between 4-FBS vs. saline vehicle control, *p<0.05, **p<0.01, ***p<0.001.

Figure 3

Shows partial reversal by ondansetron, 1mg/kg in tail flick latency protocol. Pain threshold was observed in 4-FBS 20mg/kg treated mice but it was statistically non-significant when compared with the saline vehicle control group.

Figure 4

Shows that naloxone, 1mg/kg shows partial reversal of analgesia in tail flick latency protocol. Pain threshold was observed in 4-FBS at 20mg/kg treated mice, which was statistically non-significant when compared with the saline vehicle control group.

Figure 5

Effect of 4-FBS 20 and 40mg/kg on tail flick latency time at different time-points. BALB/c mice (n=6/group) were used. 4-FBS at 20 and 40mg/kg shows significant antihyperalgesic activity in the mouse tail-flick latency time. One way ANOVA followed by Dunnett’s test shows significance difference between STZ control and 4-FBS 20mg +STZ group at all-time intervals except for 120 min while 4-FBS 40mg +STZ group at all-time. *p<0.05, **p<0.01, ***p<0.001.

Figure 6

Effect of 4-FBS 20 mg/kg on paw withdrawal threshold time at different time-points. BALB/c mice (n=6/group) were used. 4-FBS at 20 mg/kg shows significant antiallodynic activity in the paw withdrawal threshold. One way ANOVA followed by Dunnett’s test shows significance difference between STZ control and 4-FBS 20mg +STZ group at all-time intervals except for 120 min. *p<0.05, **p<0.01, ***p<0.001.

Figure 7

Effect of 4-FBS 40 mg/kg on paw withdrawal threshold time at different time-points. BALB/c mice (n=6/group) were used. 4-FBS at 40 mg/kg shows significant antiallodynic activity in the paw withdrawal threshold (n=6). One way ANOVA followed by Dunnett’s test shows significance difference between STZ control and 4-FBS 20mg +STZ group at all-time intervals except for 30 min. *p<0.05, **p<0.01, ***p<0.001.