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.