title: Niflumic acid, a TRPV1 channel modulator, ameliorates stavudine-induced neuropathic pain.
abstract: TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain. Various behavioral tests were performed to access neuropathic pain (hyperalgesia and allodynia) on 7th, 14th, 21st, and 28th days. Electrophysiology (motor nerve conduction velocity; MNCV) and biochemical estimations were conducted after 28th day. Niflumic acid (10, 15, and 20 mg/kg) was administered intraperitoneally and evaluated against behavioral, electrophysiological (MNCV), and biochemical alterations in stavudine-treated rats. Pregabalin (30 mg/kg) was taken as reference standard and administered intraperitoneally. Four weeks after stavudine injection, rats developed behavioral, electrophysiological (MNCV), and biochemical (oxidative, nitrosative stress, and inflammatory cytokines, TRPV1) alterations. Niflumic acid restored core and associated symptoms of peripheral neuropathy by suppressing oxidative-nitrosative stress, inflammatory cytokines (TNF-α, IL-1β) and TRPV1 level in stavudine-induced neuropathic pain in rats. Pharmacological efficacy of niflumic acid (20 mg/kg) was equivalent to pregabalin (30 mg/kg). In conclusion, niflumic acid attenuates STV-induced behavioral, electrophysiological and biochemical alterations by manipulating TRP channel activity in two manners: (1) direct antagonistic action against TRPV1 channels and (2) indirect inhibition of TRP channels by blocking oxidative and inflammatory surge. Therefore, NA can be developed as a potential pharmacotherapeutic adjunct for antiretroviral drug-induced neuropathy.
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India.
authors.forename: Lovish
authors.initials: L
authors.lastname: Marwaha
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India.
authors.forename: Yashika
authors.initials: Y
authors.lastname: Bansal
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India.
authors.forename: Raghunath
authors.initials: R
authors.lastname: Singh
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Saroj
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India.
authors.forename: Rupinder Kaur
authors.initials: RK
authors.lastname: Sodhi
authors.affiliation: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India. anurag_pu@yahoo.com.
authors.forename: Anurag
authors.initials: A
authors.lastname: Kuhad
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009544:Niflumic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018119:Stavudine / Q000633:toxicity*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000700:Analgesics; D015415:Biomarkers; D053583:Interleukin-1beta; D009573:Nitrites; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D009544:Niflumic Acid; D018119:Stavudine
keywords: Motor nerve conduction velocity; Neuropathic pain; Niflumic acid; Pregabalin; Stavudine; TRPV1