| Summary: | Naeem Ur Rehman,1 Mariya al-Rashida,2 Ahmed Tokhi,1 Zainab Ahmed,1 Fazal Subhan,1 Muzaffar Abbas,3 Muhammad Awais Arshid,4 Khalid Rauf1 1Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan; 2Department of Chemistry, Forman Christian College (A Chartered University), Lahore 54600, Pakistan; 3Department of Pharmacy, Capital University of Science and Technology (CUST), Islamabad, Pakistan; 4Aga Khan University Karachi, Karachi, PakistanCorrespondence: Khalid Rauf Tel + (92) 345 9824468Email khalidrauf@cuiatd.edu.pkIntroduction: 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: sulfonamides, streptozotocin; STZ, antinociception, diabetes mellitus; DM, neuropathic pain, von Frey filaments
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