Filho Paulo Ricardo Marques, Vercelino Rafael, Cioato Stefania Giotti, Medeiros Liciane Fernandes, de Oliveira Carla, Scarabelot Vanessa Leal, Souza Andressa, Rozisky Joanna Ripoll, Quevedo Alexandre da Silva, Adachi Lauren Naomi Spezia, Sanches Paulo Roberto S, Fregni Felipe, Caumo Wolnei, Torres Iraci L S
Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil; Post-Graduate Program in Biological Sciences - Physiology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:44-51. doi: 10.1016/j.pnpbp.2015.06.016. Epub 2015 Jul 7.
Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP.
Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model.
Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA.
The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05).
tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations.
神经性疼痛(NP)是一种慢性疼痛形式,通常由躯体感觉系统受损引起。NP对经典镇痛药往往反应不足,仍然是医学治疗的一个挑战。经颅直流电刺激(tDCS)是一种非侵入性技术,可在动物和人类的中枢神经系统中诱导神经可塑性变化。脑源性神经营养因子在突触可塑性过程中起重要作用。行为改变,如运动和探索活动减少以及焦虑症,是与NP相关的常见合并症。
评估tDCS治疗对建立神经性疼痛模型大鼠的运动和探索活动、焦虑样行为以及外周和中枢BDNF水平的影响。
将大鼠随机分为:假手术组(Ss)、假手术+刺激组(SsS)、假手术+经颅直流电刺激组(SsT)、神经性疼痛组(NP)、神经性疼痛+假刺激组(NpS)和神经性疼痛+经颅直流电刺激组(NpT)。在术后14天通过部分坐骨神经压迫诱导神经性疼痛模型,并开始tDCS治疗。治疗组动物接受为期8天、每次20分钟的tDCS治疗。在tDCS治疗结束后24小时(第一阶段)和7天(第二阶段)进行旷场试验和高架十字迷宫试验。通过酶联免疫吸附测定法在tDCS治疗后48小时(第一阶段)和8天(第二阶段)测定血清、脊髓、脑干和大脑皮质中的BDNF水平。
慢性缩窄性损伤(CCI)导致运动和探索活动减少、焦虑样行为增加以及脑干BDNF水平升高,最后一种情况在第二阶段出现(单因素方差分析/Student-Newman-Keuls检验,所有P<0.05)。tDCS治疗已逆转了CCI诱导的所有这些效应(单因素方差分析/Student-Newman-Keuls检验,所有P<0.05)。此外,tDCS治疗在第二阶段降低了血清和大脑皮质中的BDNF水平,并提高了脊髓中的BDNF水平(单因素方差分析/Student-Newman-Keuls检验,P<0.05)。
tDCS可逆转与神经性疼痛相关的行为改变,表明tDCS可能具有镇痛和抗焦虑作用。tDCS治疗可诱导中枢神经系统(CNS)不同区域的BDNF水平发生变化,这种效应可归因于不同的细胞信号激活。