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

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-d...

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Published in:Scientific reports Vol. 12; no. 1; pp. 17246 - 10
Main Authors: Tanaka, Satoshi, Ishida, Takashi, Ishida, Kumiko, Fuseya, Satoshi, Ito, Mariko, Sakamoto, Akiyuki, Kawamata, Mikito
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 14-10-2022
Nature Publishing Group
Nature Portfolio
Subjects:
692/1807/410/2610
692/700/565/411
Adult
Analgesics
Analgesics - therapeutic use
Animal models
Calcium Channel Blockers - therapeutic use
Capsaicin
Cross-Over Studies
Female
Healthy Volunteers
Humanities and Social Sciences
Humans
Hyperalgesia
Hyperalgesia - chemically induced
Hyperalgesia - drug therapy
Hyperpolarization
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Inflammation
Ion channels (cyclic nucleotide-gated)
Ivabradine - pharmacology
Ivabradine - therapeutic use
Male
multidisciplinary
Neuralgia
Neuralgia - chemically induced
Neuralgia - drug therapy
Nucleotides, Cyclic
Pain
Pain perception
Placebos
Science
Science (multidisciplinary)
Therapeutic targets
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Abstract 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.
AbstractList 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.
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.
Abstract 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.
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.
ArticleNumber 17246
Author Ito, Mariko
Sakamoto, Akiyuki
Kawamata, Mikito
Ishida, Takashi
Tanaka, Satoshi
Fuseya, Satoshi
Ishida, Kumiko
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36241872$$D View this record in MEDLINE/PubMed
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  publication-title: Lancet
  doi: 10.1016/S0140-6736(10)61198-1
  contributor:
    fullname: K Swedberg
– volume: 160
  start-page: 2554
  year: 2019
  ident: 22309_CR24
  publication-title: Pain
  doi: 10.1097/j.pain.0000000000001638
  contributor:
    fullname: MC Lee
– volume: 14
  start-page: e0217209
  year: 2019
  ident: 22309_CR12
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0217209
  contributor:
    fullname: S Miyake
– volume: 64
  start-page: 722
  year: 2012
  ident: 22309_CR14
  publication-title: Pharmacol. Rev.
  doi: 10.1124/pr.111.005447
  contributor:
    fullname: AE Olesen
SSID ssj0000529419
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Snippet Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been focused on as a potential therapeutic target for inflammatory and neuropathic pain...
Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been focused on as a potential therapeutic target for inflammatory and...
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StartPage 17246
SubjectTerms 692/1807/410/2610
692/700/565/411
Adult
Analgesics
Analgesics - therapeutic use
Animal models
Calcium Channel Blockers - therapeutic use
Capsaicin
Cross-Over Studies
Female
Healthy Volunteers
Humanities and Social Sciences
Humans
Hyperalgesia
Hyperalgesia - chemically induced
Hyperalgesia - drug therapy
Hyperpolarization
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Inflammation
Ion channels (cyclic nucleotide-gated)
Ivabradine - pharmacology
Ivabradine - therapeutic use
Male
multidisciplinary
Neuralgia
Neuralgia - chemically induced
Neuralgia - drug therapy
Nucleotides, Cyclic
Pain
Pain perception
Placebos
Science
Science (multidisciplinary)
Therapeutic targets
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Title A randomized, double-blinded, placebo-controlled, crossover study of the HCN channel blocker ivabradine in a capsaicin-induced pain model in healthy volunteers
URI https://link.springer.com/article/10.1038/s41598-022-22309-7
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Volume 12
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