Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Neuromodulation. 2012 Jul;15(4):283-95. doi: 10.1111/j.1525-1403.2012.00478.x. Epub 2012 Jul 3.
Noninvasive brain stimulation (NIBS) interventions have demonstrated promising results in the clinical treatment of pain, according to several preliminary trials, although the results have been mixed. The limitations of clinical research on NIBS are the insufficient understanding of its mechanisms of action, a lack of adequate safety data, and several disparities with regard to stimulation parameters, which have hindered the generalizability of such studies. Thus, experimental animal research that allows the use of more invasive interventions and creates additional control of independent variables and confounders is desirable. To this end, we systematically reviewed animal studies investigating the analgesic effects of NIBS. In addition, we also explored the investigation of NIBS in animal models of stroke as to compare these findings with NIBS animal pain research.
Of 1916 articles that were found initially, we identified 15 studies (stroke and pain studies) per our eligibility criteria that used NIBS methods, such as transcranial direct current stimulation, paired associative stimulation, transcranial magnetic stimulation, and transcranial electrostimulation. We extracted the main outcomes on stroke and pain, as well as the methods and electrical parameters of each technique.
NIBS techniques are effective in alleviating pain. Similar beneficial clinical effects are observed in stroke. The main insights from these animal studies are the following: 1) combination of NIBS with analgesic drugs has a synergistic effect; 2) effects are dependent on the parameters of stimulation, and in fact, not necessarily the strongest stimulation parameter (i.e., the largest intensity of stimulation) is associated with the largest benefit; 3) pain studies show an overall good quality as indexed by Animals in Research: Reporting In Vivo Experiments guidelines of the reporting of animal experiments, but insufficient with regard to the reporting of safety data for brain stimulation; 4) these studies suggest that NIBS techniques have a primary effect on synaptic plasticity, but they also suggest other mechanisms of action such as via neurovascular modulation.
We found a limited number of animal studies for both pain and stroke NIBS experimental research. There is a lack of safety data in animal studies in these two topics and results from these studies have not been yet fully tested and translated to human research. We discuss the challenges and limitations of translating experimental animal research on NIBS into clinical studies.
根据几项初步试验，非侵入性脑刺激（NIBS）干预措施在疼痛的临床治疗中显示出有希望的结果，但结果喜忧参半。NIBS 临床研究的局限性在于对其作用机制的理解不足、缺乏足够的安全性数据以及刺激参数方面的几个差异，这些都阻碍了此类研究的推广。因此，需要进行实验动物研究，以便使用更具侵入性的干预措施，并对自变量和混杂因素进行额外控制。为此，我们系统地回顾了研究 NIBS 镇痛作用的动物研究。此外，我们还探讨了在卒中动物模型中进行 NIBS 的研究，以将这些发现与 NIBS 动物疼痛研究进行比较。
在最初发现的 1916 篇文章中，我们根据纳入标准确定了使用 NIBS 方法（如经颅直流电刺激、成对关联刺激、经颅磁刺激和经颅电刺激）的 15 项研究（卒中研究和疼痛研究）。我们提取了关于卒中和疼痛的主要结果，以及每种技术的方法和电参数。
NIBS 技术可有效缓解疼痛，在卒中患者中也观察到类似的有益临床效果。这些动物研究的主要发现如下：1）NIBS 与镇痛药联合使用具有协同作用；2）效果取决于刺激参数，实际上，不一定是最强的刺激参数（即最大刺激强度）与最大益处相关；3）疼痛研究根据动物实验报告的实验动物报告准则总体质量较好，但关于脑刺激的安全性数据报告不足；4）这些研究表明，NIBS 技术对突触可塑性具有主要作用，但也表明了其他作用机制，如通过神经血管调节。
我们发现针对疼痛和卒中的 NIBS 实验研究的动物研究数量有限。这两个主题的动物研究缺乏安全性数据，并且这些研究的结果尚未得到充分验证和转化为人类研究。我们讨论了将 NIBS 实验动物研究转化为临床研究的挑战和局限性。
