Baek In Seon, Choi Seunghwan, Yoon Heera, Chung Geehoon, Kim Sun Kwang
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Exp Neurobiol. 2024 Jun 30;33(3):129-139. doi: 10.5607/en24012.
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, α-, α-, 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.
癌症化疗常常会引发患者的周围神经病变，导致四肢出现神经性疼痛。尽管先前的研究探索了各种神经刺激方法来缓解化疗引起的周围神经病变（CIPN），但关于非侵入性耳迷走神经刺激（aVNS）有效性的证据仍不明确。本研究旨在调查非侵入性aVNS缓解CIPN疼痛的疗效。为了在实验动物中诱导CIPN，给大鼠腹腔注射奥沙利铂（6毫克/千克）。分别使用von Frey试验和丙酮试验评估神经性疼痛的代表性症状——机械性异常性疼痛和冷异常性疼痛。将CIPN动物随机分组，并用不同频率（2、20或100赫兹）的aVNS（5伏，方波）治疗20分钟。结果显示，20赫兹的aVNS表现出最显著的镇痛效果，而2或100赫兹的aVNS效果较弱。免疫组织化学分析表明，与假手术治疗相比，接受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行通路的镇痛机制，在20赫兹aVNS之前，将α-、α-或β-肾上腺素能受体拮抗剂注入脊髓。只有β-肾上腺素能受体拮抗剂普萘洛尔阻断了aVNS的镇痛作用。这些发现表明，20赫兹的aVNS可能通过激活β-肾上腺素能受体有效缓解CIPN疼痛。
