Avaliação do efeito da crotalfina injetada nos acupontos Zusanli (E36) e Kunlun (B60) combinado com eletroacupuntura na dor neuropática induzida por paclitaxel em ratos

Abstract

Neuropathic pain (NP) can be caused by the adverse effect of chemotherapy using paclitaxel (PAC). In this context, covering strategies for the management of NP, studies have shown that crotalphine (CRO) is a synthetic peptide that induces a potent and long-lasting antinociceptive effect dependent on the release of endogenous opioids in different pain models. Thus, pharmacopuncture is a technique that uses the administration of drugs or animal toxins concomitantly in acupoints. Preclinical studies show an antinociceptive effect of electroacupuncture (EA) of the Zusanli (E36) and Kunlun (B60) acupoints for analgesic effects. Therefore, this study aimed to investigate the antinociceptive effect of pharmacopuncture with CRO associated or not with EA treatment at different frequencies in PAC-induced NP. The animals received intraperitoneal injections of PAC every other day, totaling four administrations (for example: days 0, 2, 4 and 6). The groups were divided into three: preemptive (Gpreemp), during (Gind) and treatment (Gtrat) of PAC-induced NP and treated with local administration of CRO at acupoints E36 and B60. They were then treated with EA at frequencies of 2 Hz or 2/15Hz for 30 minutes. Behavioral assessment with Vonfrey (mechanical threshold), acetone test (cold allodynia) and open field was carried out in all groups. In addition, the Western Blotting assay was used to evaluate the expression of astrocyte (GFAP) markers in specific samples from the treatment group. It was shown that EA 2/15Hz and 2Hz on the Zusanli and Kunlun acupoints promoted an increase in the mechanical threshold and a decrease in cold allodynia in the animals in the treatment, during and preemptive groups. In addition, the groups that received pharmacopuncture with CRO as treatment also obtained results in increased mechanical threshold and decreased cold allodynia. The data show that the combination of 2Hz or 2/15Hz EA associated with pharmacopuncture with CRO was able to reduce mechanical and cold allodynia in both experimental groups (preemptive, during and pain treatment) when compared to their controls, indicating an antinociceptive effect. In the animals in the treatment group that underwent PAC, it was possible to observe an increase in astrocyte marker expression and the use of 2Hz EA associated with pharmacopuncture with CRO was able to reduce the expression of astrocyte markers in these animals. Therefore, the combination of CRO pharmacopuncture and 2Hz or 2/15Hz EA produced an antinociceptive effect in the preventive, induction and during groups in an animal model of PAC-induced NP.