Efeito da neuroestimulação e da inativação da divisão infra-límbica do córtex pré-frontal medial sobre a antinocicepção induzida pela eletroacupuntura de 2Hz e 2/100Hz em animais com dor neuropática crônica

Abstract

Chronic neuropathic pain (NP) can be referred to as pain initiated by injury or dysfunction of the somatosensory nervous system, being an abnormal activation of the nociceptive pathway. Cortical and subcortical networks are activated by pain, including sensory, limbic and associative regions. The medial prefrontal cortex (MPFC) is an important region in the elaboration of its cognitive and emotional aspects. There is evidence that a chronic pain (CP) of neuropathic origin is capable of causing morphological changes, resulting in a reorganization in the CPFM neural networks. Electroacupuncture (EA) appears in this context as a therapeutic modality of oriental medicine for the treatment and relief of CP. Due to the scarcity of studies that study the participation of CP and the participation of cortical areas of the MPFC, the present study evaluated the participation of the infralimbic MPFC (IFL) on the effect of analgesia induced by electroacupuncture (AIEA) of 2Hz or 2/100Hz and the association of cortical neurostimulation using deep brain stimulation equipment (DBS) in an animal model of CP of neuropathic origin. In this study, male Wistars rats with an initial weight of 100g were used. Initially, all animals were analyzed with nociceptive tests at baseline 1 (BL1), with von Frey (mechanical allodynia) and the acetone test (cold allodynia). Then, the groups were induced to injury by chronic constriction (ICC) of the sciatic nerve or neuropathy (Sham) was simulated. After fourteen (14) days, the animals were submitted to stereotactic surgery for the implantation of the guide cannula at MPFC IFL. Subsequently, after twenty-one (21) days, the mechanical nociceptive test and the cold test were analyzed again at baseline 2 (BL2), and then, treatment with 2Hz EA, 2A / 100Hz, Sham EA (EA off) and / or out (EA on and 5 millimeter outside the acupoints), in the Zusanli (S36) and Sanyinjiao (SP6) acupoints, for 20 minutes. Immediately at the end of the EA, saline (0.9% NaCl / 200nL) or cobalt chloride (1mM / 200nL) were administered via independent guide cannula MPFC. After 10 minutes, mechanical and cold allodynia tests were performed again at times 10, 20, 30, 60 and 180 minutes. In addition, independent groups of animals received neurostimulation of the IFL cortex immediately after the 2Hz EA and 2 / 100Hz EA with deep brain stimulation equipment (DBS: at 20µA for 15s). We demonstrated that EA of 2 Hz and EA of 2 / 100Hz in acupoints E36 and BP6 produced AIEA at the threshold of mechanical allodynia and cold allodynia of animals with chronic NP. In addition, we can suggest that MPFC IFL is involved in the AIEA, since, by microinjecting CoCL2 in MPFC IFL, the mechanical and cold allodynia in animals decreased. When associating EA of 2Hz and EA of 2 / 100hz at points E36 and BP6 with neurostimulation in CPFM IFL with DBS, there was AIEA in both frequencies, however, in the frequency of 2Hz the AIEA was enhanced. Thus, we show that the 2Hz EA and the 2 / 100Hz EA produces antinociception through the activation of the CPFM IFL and that the 2HZ EA seems to be the frequency that depends on the activation of the CPFM IFL, and that it is enhanced by combination between DBS and 2 Hz EA in Wistar rats with chronic neuropathic pain.