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.