Lin Huan-Chin, Park Hi-Joon, Liao Hsien-Yin, Chuang Kai-Ting, Lin Yi-Wen
College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 404328, Taiwan.
Department of Traditional Chinese Medicine, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung 420255, Taiwan.
Life (Basel). 2025 May 20;15(5):819. doi: 10.3390/life15050819.
Fibromyalgia, one of the most challenging pains to treat, lacks impartial considerations for diagnosis and useful assessment. The core symptoms are persistent extensive pain accompanied by fatigue, psychological disorders, sleep disturbance, and obesity. This study aims to explore the role of cannabinoid receptor 1 (CB1) on transient receptor potential V1 (TRPV1) signaling pathways in a mouse model of fibromyalgia. This model was subjected to intermittent cold stress (ICS) to induce fibromyalgia, as measured by the nociceptive behavior determined by von Frey and Hargreaves' tests. Our results showed a lower mechanical threshold (2.32 ± 0.12 g) and thermal latency (4.14 ± 0.26 s) in ICS-induced fibromyalgia mice. The hyperalgesia could be alleviated by 2 Hz electroacupuncture (EA) or by TRPV1 knockout. We found decreased CB1 receptors, upregulated TRPV1, and related kinases in the dorsal root ganglion, spinal cord, hypothalamus, and periaqueductal gray in fibromyalgia mice. EA reversed these effects associated with fibromyalgia, aligning with observations in mice. Peripheral acupoint or the intracerebral ventricle injection of a CB1 agonist significantly attenuated mechanical and thermal hyperalgesia. The EA analgesic effect was reversed by a CB1 antagonist injection, suggesting the involvement of the CB1 signaling pathway. The accurate chemogenetic activation of paraventricular nucleus (PVN), which is a structure of the hypothalamus, initiated fibromyalgia pain. The chemogenetic inhibition of PVN attenuated fibromyalgia pain via the downregulation of TRPV1 pathway. Our discoveries shed light on the involvement of CB1 in the TRPV1 signaling pathway in the effects of EA in fibromyalgia, suggesting its potential as a treatment target.
纤维肌痛是最难治疗的疼痛之一，在诊断和有效评估方面缺乏公正的考量。其核心症状是持续性广泛疼痛，并伴有疲劳、心理障碍、睡眠障碍和肥胖。本研究旨在探讨大麻素受体1（CB1）在纤维肌痛小鼠模型中对瞬时受体电位香草酸亚型1（TRPV1）信号通路的作用。该模型通过间歇性冷应激（ICS）诱导纤维肌痛，通过von Frey和哈格里夫斯试验测定的伤害性感受行为来衡量。我们的结果显示，ICS诱导的纤维肌痛小鼠的机械阈值较低（2.32±0.12克），热潜伏期较短（4.14±0.26秒）。2赫兹电针（EA）或TRPV1基因敲除可减轻痛觉过敏。我们发现纤维肌痛小鼠的背根神经节、脊髓、下丘脑和导水管周围灰质中的CB1受体减少，TRPV1及其相关激酶上调。EA逆转了与纤维肌痛相关的这些效应，与在小鼠中的观察结果一致。外周穴位或脑室内注射CB1激动剂可显著减轻机械性和热性痛觉过敏。注射CB1拮抗剂可逆转EA的镇痛作用，表明CB1信号通路参与其中。下丘脑结构室旁核（PVN）的精确化学遗传激活引发了纤维肌痛疼痛。PVN的化学遗传抑制通过下调TRPV1通路减轻了纤维肌痛疼痛。我们的发现揭示了CB1在EA对纤维肌痛的作用中参与TRPV1信号通路，表明其作为治疗靶点的潜力。
