Vitaminas do complexo B como potenciais fármacos para o manejo da dor neuropática induzida por quimioterápico.

Abstract

The management of chemotherapy-induced neuropathic pain (CINP) is still challenging due to the lack of drugs that may effectively prevent or alleviate this condition. Drug repositioning is a process that has been stimulated in order to identify new pharmacotherapeutic approaches that may be useful for the management of neuropathic pain. B vitamins, particularly thiamine, nicotinamide and riboflavin, have been investigated aiming the repositioning for prevention or relief of CINP. Preclinical trials have shown that these some B vitamins exhibit activity in various models of acute and chronic pain and inflammation. The objective of this study was to evaluate the effects induced by some B vitamins on the mechanical allodynia in an experimental model of neuropathic pain induced by paclitaxel. The evaluation of the effect induced by thiamine (150, 300 or 600 mg/Kg, per os – p.o.), nicotinamide (250, 500 or 1000 mg/Kg, p.o.) or riboflavin (125, 250 and 500 mg/Kg, p.o.) on the mechanical allodynia induced by paclitaxel (four doses, 2 mg/Kg, 2 mL/Kg, intraperitoneal – i.p.) was carried out on mice. To investigate potential mechanisms mediating the antinociceptive activity of the vitamins, opioidergic (naltrexone, 5 or 10 mg/Kg, i.p.) and serotonergic (cyproheptadine, 5 or 10 mg/Kg, i.p.) antagonists and an ATP-sensitive potassium channels (KATP) blocker (glibenclamide, 20 or 40 mg/Kg, p.o.) were used. The effect of B vitamins on the concentration of inflammatory cytokines (tumor necrosis factor-α and CXCL-1) in the dorsal root ganglia (DRG) and thalamus was also evaluated. B vitamins inhibited paclitaxel-induced mechanical allodynia when administered twice daily on the seventh day after sensitization, with antinociceptive activities similar to that of pregabalin (30 mg/Kg, p.o.). These activities were not associated with impairment of motor coordination. Naltrexone and glibenclamine attenuated the antinociceptive effect induced by thiamine and riboflavin. Nicotinamide antinociceptive effect was attenuated only by glibenclamide. B vitamins reduced the concentrations of inflammatory cytokines in the DRG and thalamus. The results demonstrate that B vitamins antinociceptive activity in the neuropathic pain model induced by paclitaxel is mediated by activation of opioidergic receptors and/or KATP channels, as well as reduced production of inflammatory cytokines in DRG and thalamus. Concluding, B vitamins may represent a new pharmacotherapeutic strategy in the management of patients with CINP, justifying the conduction of additional preclinical and clinical trials, in order to evaluate their potential use as an analgesic drug