Abstract
Some B vitamins exhibit activities in models of nociceptive pain, inflammatory pain, and neuropathic pain induced by nerve lesions and also in certain painful conditions in humans. In the present study, we investigated the effects of thiamine, riboflavin, and nicotinamide in a neuropathic pain model induced by the chemotherapeutic paclitaxel in mice. Four intraperitoneal (i.p.) administrations of paclitaxel (2 mg/kg day, cumulative dose 8 mg/kg) induced a long-lasting mechanical allodynia. Per os (p.o.) administration of two doses of thiamine (150, 300 and 600 mg/kg), nicotinamide (250, 500 and 1000 mg/kg) or riboflavin (125, 250 and 500 mg/kg), on the seventh day after the first administration of paclitaxel, the mechanical allodynia was attenuated. The antinociceptive activity of all B vitamins was attenuated by glibenclamide (20 and 10 mg/kg, p.o.). Naltrexone (5 and 10 mg/kg, i.p.) attenuated the antinociceptive activity of thiamine. Thiamine, riboflavin, and nicotinamide also reduced the concentrations of tumor necrosis factor-α (TNF-α) and CXCL-1 in dorsal root ganglia (DRG) and thalamus. In conclusion, thiamine, riboflavin, and nicotinamide exhibit antinociceptive activity in the neuropathic pain model induced by paclitaxel. Inhibition of TNF-α and CXCL-1 production in DRG and thalamus, as well as activation of ATP-sensitive potassium channels, underly their antinociceptive activity.
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We thank Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG; APQ-03027-18), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 303307/2018-8), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001) and Pró-Reitoria de Pesquisa/UFMG for financial support.
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AVB contributed to the research design, performance of the experiment and data analysis. SOAMC, FFR, ISFM and MIM contributed to the performance of the experiment and data analysis. The study was conceived and supervised by MMC and RRM. All authors edited, read and approved the final manuscript.
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Braga, A.V., Costa, S.O.A.M., Rodrigues, F.F. et al. Thiamine, riboflavin, and nicotinamide inhibit paclitaxel-induced allodynia by reducing TNF-α and CXCL-1 in dorsal root ganglia and thalamus and activating ATP-sensitive potassium channels. Inflammopharmacol 28, 201–213 (2020). https://doi.org/10.1007/s10787-019-00625-1
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DOI: https://doi.org/10.1007/s10787-019-00625-1