PDF(Pubmed)
Abstract：
Cancer chemotherapy often triggers peripheral neuropathy in patients, leading to neuropathic pain in the extremities. While previous research has explored various nerve stimulation to alleviate chemotherapy-induced peripheral neuropathy (CIPN), evidence on the effectiveness of noninvasive auricular vagus nerve stimulation (aVNS) remains uncertain. This study aimed to investigate the efficacy of non-invasive aVNS in relieving CIPN pain. To induce CIPN in experimental animals, oxaliplatin was intraperitoneally administered to rats (6 mg/kg). Mechanical and cold allodynia, the representative symptoms of neuropathic pain, were evaluated using the von Frey test and acetone test, respectively. The CIPN animals were randomly assigned to groups and treated with aVNS (5 V, square wave) at different frequencies (2, 20, or 100 Hz) for 20 minutes. Results revealed that 20 Hz aVNS exhibited the most pronounced analgesic effect, while 2 or 100 Hz aVNS exhibited weak effects. Immunohistochemistry analysis demonstrated increased c-Fos expression in the locus coeruleus (LC) in the brain of CIPN rats treated with aVNS compared to sham treatment. To elucidate the analgesic mechanisms involving the adrenergic descending pathway, α1-, α2-, or β-adrenergic receptor antagonists were administered to the spinal cord before 20 Hz aVNS. Only the β-adrenergic receptor antagonist, propranolol, blocked the analgesic effect of aVNS. These findings suggest that 20 Hz aVNS may effectively alleviate CIPN pain through β-adrenergic receptor activation.
摘要：
癌症化疗通常会引发患者的周围神经病变，导致四肢神经性疼痛。虽然先前的研究已经探索了各种神经刺激来减轻化疗引起的周围神经病变（CIPN），关于无创耳迷走神经刺激(aVNS)有效性的证据仍不确定.本研究旨在探讨非侵入性aVNS在缓解CIPN疼痛中的疗效。在实验动物中诱导CIPN，大鼠腹腔注射奥沙利铂(6mg/kg)。机械性和冷异常性疼痛，神经性疼痛的代表性症状，使用vonFrey测试和丙酮测试进行评估，分别。TheCIPN动物被随机分组并接受aVNS治疗(5V，方波）在不同频率（2、20或100Hz）下进行20分钟。结果显示，20HzaVNS表现出最明显的镇痛作用，而2或100HzaVNS表现出弱作用。免疫组织化学分析表明，与假手术相比，用aVNS治疗的CIPN大鼠大脑蓝斑（LC）中的c-Fos表达增加。为了阐明涉及肾上腺素能下降通路的镇痛机制，α1-,α2-,或β-肾上腺素能受体拮抗剂在20HzaVNS之前给予脊髓。只有β-肾上腺素受体拮抗剂，普萘洛尔,阻断aVNS的镇痛作用。这些发现表明，20HzaVNS可能通过激活β-肾上腺素能受体有效缓解CIPN疼痛。
