AfaSci Research Laboratories , Redwood City, California 94063, United States.
School of Electronics and Information Technology; State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-Sen University , Guangzhou 510275, China.
ACS Nano. 2017 Jan 24;11(1):395-406. doi: 10.1021/acsnano.6b06104. Epub 2016 Dec 27.
Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.
神经损伤引起的神经性疼痛使人虚弱,难以治疗。目前用于神经性疼痛的全身性药物治疗方法只能有限地缓解疼痛,且具有不良的副作用,而目前的局部麻醉剂往往会非特异性地阻断感觉和运动功能。降钙素基因相关肽(CGRP)是一种从感觉神经末梢释放的神经肽,似乎在慢性神经性疼痛中起着重要作用。在这项研究中,我们开发了一种镇痛微针贴片(AMN),使用可溶解微针以无痛的方式经皮递送至选择性 CGRP 拮抗剂肽,用于治疗局部神经性疼痛。通过使用神经性疼痛模型(如 spared-nerve injury 和糖尿病性神经病痛)以及紫外线 B(UVB)辐射诱导的神经源性炎症性疼痛模型,在大鼠中评估局部镇痛效果,以测试对热和机械刺激的行为疼痛敏感性。与几种传统疗法不同,AMN 贴片对神经性疼痛产生了有效的镇痛作用,而不会干扰大鼠的正常伤害感受和运动功能,这是由于递送至 CGRP 受体的肽具有很高的特异性。AMN 贴片不会引起皮肤刺激或全身副作用。这些结果表明,递送至 CGRP 拮抗剂肽的可溶解微针贴片提供了一种有效、安全且简单的方法来减轻神经性疼痛,与当前的治疗方法相比具有显著优势。