The protective effect of modafinil on vincristine-induced peripheral neuropathy in rats: A possible role for TRPA1 receptors.
Vincristine (VCR) induces peripheral neuropathy. We aimed to assess the efficacy of modafinil on VCR-induced neuropathy in rats. Neuropathy was induced by intraperitoneal (i.p.) injections of VCR (0.1 mg/kg). Neuropathic groups received modafinil (5, 25 and 50 mg/kg); gabapentin (20 mg/kg); and a combination of modafinil (5 and 50 mg/kg) and gabapentin (20 mg/kg,). Then, electrophysiological, behavioural, biochemical and pathological evaluations were performed. Latencies of tail-flick and von Frey filament tests, motor nerve conduction velocity (MNCV) and excitation of nerve conduction were decreased. Moreover, the transient receptor potential cation channel ankyrin 1 (TRPA1) level was increased, while TRPV1 and N-Methyl-D-aspartate (NMDA) levels remained unchanged. Tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) levels were markedly elevated. Pre-treatment with modafinil prevented sensorimotor neuropathy by raising latencies, MNCV and excitation, reducing TRPA1, TNF-α and IL-1β levels. Modafinil improved behavioural, electrophysiological and pathological disturbances. The results showed that TRPA1 has a more important role than NMDA and TRPV1, in VCR-induced neuropathic pain. In addition, inflammatory mediators, TNF-α and IL-1β, were involved. Further, the combination of modafinil and gabapentin improved the neuroprotective effect of gabapentin. So, modafinil might be a neuroprotective agent in the prevention of VCR-induced neuropathy.
['Amirkhanloo|Fatemeh|F|https://orcid.org/0000-0003-0490-3648', 'Karimi|Gholamreza|G|', 'Yousefi-Manesh|Hasan|H|', 'Abdollahi|Alireza|A|', 'Roohbakhsh|Ali|A|', 'Dehpour|Ahmad Reza|AR|']
D000818:Animals D016207:Cytokines D000077206:Gabapentin D006930:Hyperalgesia D053583:Interleukin-1beta D000077408:Modafinil D009431:Neural Conduction D009437:Neuralgia D018696:Neuroprotective Agents D051381:Rats D017208:Rats, Wistar D012584:Sciatic Nerve D000074025:TRPA1 Cation Channel D014409:Tumor Necrosis Factor-alpha D014750:Vincristine
modafinil peripheral neuropathy TRPA1 vincristine gabapentin TRPV1 NMDA TNF-α IL-1β DRG neurons