Revisão sistemática e metanálise do efeito analgésico do ácido alfa-lipóico em estudos clínicos e atividade antinociceptiva em um modelo de SDCR tipo I

Abstract

Chronic pain is a common type of disabling pain, which may or may not be related to other pathologies. It is known that oxidative stress generates compounds that activate ion channels, which are related to increased pain and neuroinflammation. In this view, treatment with antioxidants stands out, since the release of free radicals is observed in both diabetic polyneuropathy and CRPS-I.. The compound ɑ-lipoic acid (ALA) is a potent antioxidant that has an analgesic effect in the treatment of different types of pain. Thus, the aim of this study was to carry out a systematic review and meta-analysis on the effectiveness of the ALA compound in controlling chronic pain. Furthermore, to evaluate the antinociceptive activity and the effect on neuroinflammation in a model of CRPS I. To this end, the systematic review was performed according to the PRISMA 2020 checklist guidelines for data reporting, and registered in PROSPERO (CRD42021261971), at the end of the search, 16 randomized clinical trials were selected for study. The results found in the systematic review evidenced the use of ALA compound in pain symptoms induced mainly for diabetic polyneuropathy. The meta-analysis was performed only with studies on diabetic polyneuropathy, which was observed that when compared to the placebo group, the group treated with ALA decreased the total symptom score (TSS), a type of pain measure. However, more studies must be carried out with the purpose of standardizing treatment time and dose, in order to advance towards the approval of ALA compound for clinical treatment in diabetic polyneuropathy. For the in vivo study, male C57BL/6 mice were used to induce chronic post-ischemia pain (CPIP), a CRPS-I model. The induction of mechanical (von Frey test) and cold allodynia (acetone test), locomotor parameters (rotating cylinder and open field tests) and nest building behavior were evaluated. Moreover, 16 days after CPIP or control, oxidative stress (levels of hydrogen peroxide, NADPH oxidase and superoxide dismutase activity) or neuroinflammation (Iba1, Nrf2 and Gfap) were observed. Repeated treatment with ALA (100 mg/kg) intragastrically for 15 days after CPIP reduced CPIP-induced mechanical and cold allodynia and restored nest-building ability without causing locomotor impairment. The treatment reduced the activity of superoxide dismutase and NADPH oxidase and the production of hydrogen peroxide. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. Thus, repeated treatment with ALA was able to treat and prevent nociception by reducing oxidative stress and neuroinflammation associated with a model of CRPS-I in mice.