A randomized, double-blinded, placebo-controlled, crossover study of the HCN channel blocker ivabradine in a capsaicin-induced pain model in healthy volunteers.
A randomized, double-blinded, placebo-controlled, crossover study of the HCN channel blocker ivabradine in a capsaicin-induced pain model in healthy volunteers.
复制标题
DOI：
10.1038/s41598-022-22309-7
复制
发表时间：
2022-10-14
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
超极化激活的环核苷酸门控（HCN）通道已被重点作为一个潜在的治疗目标，炎症和神经病理性疼痛的啮齿动物模型。然而，HCN通道在人类疼痛状态中的作用却很少被研究。我们在一项随机、双盲、安慰剂对照、交叉研究中评价了伊伐布雷定（唯一临床可用的HCN通道阻滞剂）给药2天对辣椒素疼痛模型的镇痛作用。20例健康成人受试者（18例男性，2例女性）在2天内接受伊伐布雷定（5-7.5 mg）或安慰剂3次。然后将辣椒素（0.5%）局部施用于前臂掌侧30分钟。主要结果是辣椒素诱导的自发性疼痛。次要结局包括热痛阈值（HPT）、耀斑大小、继发性点状机械性痛觉过敏（PMH）和继发性动态机械性异常性疼痛（DMA）的面积。在辣椒素应用后30分钟，两组之间的自发性疼痛（p = 0.7479）、HPT（p = 0.7501）、PMH面积（p = 0.1052）或耀斑大小（p = 0.5650）没有显著差异。相比之下，伊伐布雷定组的DMA面积显著小于安慰剂组（p < 0.001）。HCN通道可能差异参与人类的各种疼痛信号传递途径。
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been focused on as a potential therapeutic target for inflammatory and neuropathic pain in rodent models. However, roles of HCN channels in human pain states have been scarcely investigated. We evaluated analgesic effects of 2-day administration of ivabradine, the only clinically available HCN channel blocker, on a capsaicin pain model in a randomized, double-blinded, placebo-controlled, crossover study. Twenty healthy adult subjects (18 males, 2 females) received ivabradine (5–7.5 mg) or a placebo 3 times in 2 days. Then capsaicin (0.5%) was topically applied on the volar forearm for 30 min. The primary outcome was capsaicin-induced spontaneous pain. The secondary outcomes included heat-pain threshold (HPT), flare size, and areas of secondary punctate mechanical hyperalgesia (PMH) and secondary dynamic mechanical allodynia (DMA). There was no significant difference in spontaneous pain (p = 0.7479), HPT (p = 0.7501), area of PMH (p = 0.1052) or flare size (p = 0.5650) at 30 min after capsaicin application between the groups. In contrast, the area of DMA in the ivabradine group was significantly smaller (p < 0.001) than that in the placebo group. HCN channels may be differentially involved in the various pain signal transmission pathways in humans.
登录
查看更多内容
影响因子：
7.7
作者：
Krämer, HH;Schmelz, M;Bickel, A
通讯作者：
Bickel, A
影响因子：
14.5
作者：
Magerl, W;Fuchs, PN;Treede, RD
通讯作者：
Treede, RD
影响因子：
7.4
作者：
La JH;Chung JM
通讯作者：
Chung JM
影响因子：
3.2
作者：
Choi, Hee Youn;Noh, Yook-Hwan;Lim, Hyeong-Seok
通讯作者：
Lim, Hyeong-Seok
影响因子：
3.2
作者：
Jiang, Juanjuan;Tian, Lei;Xu, Li
通讯作者：
Xu, Li