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Niflumic acid, a TRPV1 channel modulator, ameliorates stavudine-induced neuropathic pain

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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.

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Acknowledgments

Research grants sanctioned by SERB, Department of Science and Technology (DST), All India Council of Technical Education (F. No. 11-25/RIFD/CAYT/POL-II/2013-14) and University Grants Commission (UGC), New Delhi to Dr. Anurag Kuhad are gratefully acknowledged. Junior Research Fellowship sanctioned by AICTE, New Delhi to Mr. Lovish Marwaha is also gratefully acknowledged.

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  1. Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India

    Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Rupinder Kaur Sodhi & Anurag Kuhad

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  1. Lovish Marwaha
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  2. Yashika Bansal
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  3. Raghunath Singh
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Correspondence to Anurag Kuhad.

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Marwaha, L., Bansal, Y., Singh, R. et al. Niflumic acid, a TRPV1 channel modulator, ameliorates stavudine-induced neuropathic pain. Inflammopharmacol 24, 319–334 (2016). https://doi.org/10.1007/s10787-016-0285-0

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