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

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 5HT 3 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.

Effects of 1-methyl-1, 2, 3, 4-tetrahydroisoquinoline on a diabetic neuropathic pain model

“…The experimenters were not blinded to overall drug treatment since diabetic mice have distinct physical care requirements, for example, the bedding in cages was changed on alternate days to provide dry bedding because animals displayed polyuria. Animals having a heightened pain response to mechanical pressure by means of manual von Frey filament application with a minimal starting pressure (0.008 g) upwards and thermal stimulus (decreased in tail-flick latency) confirmed the onset of the DPN in the model ( Zhao et al, 2015 ; Rehman et al, 2020a ; Rehman et al, 2020b ). Following STZ injection, a few mice were excluded from the study, as they did not develop diabetes, or they died (6 mice died within 72 h post-STZ administration and 2 expired during experimentation).…”

“…Subsequently, the supernatant was filtered using a 0.45 mm filter (CNW Technologies). It was then placed for analysis in an HPLC auto-sampler ( Rehman et al, 2020a ; Rehman et al, 2020b ).…”

“…Samples were then placed in an HPLC auto-sampler and 20 µL volume was withdrawn for injection using the software (Empower TM ). The calibration curve was then constructed by plotting the peak area of dopamine, serotonin or noradrenaline (y) against the concentration of standard dopamine, serotonin or noradrenaline (x) respectively, using linear regression analysis ( Rehman et al, 2020a ; Rehman et al, 2020b ).…”

“…The UV detection wavelength was 280 nm with isocratic elution. The elution rate was set at a flow rate of 0.5 mL/min and a column temperature of 35°C ( Hou et al, 2019 ; Rehman et al, 2020a ; Rehman et al, 2020b ).…”