ArticleMolecular pain2012
Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K(2P)) and voltage-gated (K(v)1.1 and K(v)1.2) potassium channels.
Article in Molecular pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Article
- Genetic Variants inInternational journal of molecular sciences · 2025Article
- Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk.Frontiers in pharmacology · 2022Review
- GI-530159, a novel, selective, mechanosensitive two-pore-domain potassium (KBritish journal of pharmacology · 2018Article
- TLR7 agonist-induced bronchodilation: key mechanistic questions remain.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Trp channels and itch.Seminars in immunopathology · 2016Review
- Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain.Pflugers Archiv : European journal of physiology · 2015Review
- Targeting TRP ion channels for itch relief.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- TLR4 enhances histamine-mediated pruritus by potentiating TRPV1 activity.Molecular brain · 2014Article
- Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons.Neuroscience bulletin · 2014Review
- Itch mechanisms and circuits.Annual review of biophysics · 2014Review
- New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?Pflugers Archiv : European journal of physiology · 2013Review
- Neural processing of itch.Neuroscience · 2013Review
- TLR7 negatively regulates dendrite outgrowth through the Myd88-c-Fos-IL-6 pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Novel role of KT5720 on regulating hyperpolarization-activated cyclic nucleotide-gated channel activity and dorsal root ganglion neuron excitability.DNA and cell biology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons.
findingsWhen IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K(+) channels, K(v)1.1 and K(v)1.2 (voltage-gated K(+) channels) and TREK1 and TRAAK (K(2P) channels). IQ effectively reduced the currents mediated by both K(+) channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K(v)1.1 and K(v)1.2.
conclusionsOur results demonstrate that IQ blocks the voltage-gated K(+) channels to increase AP duration and K(2P) channels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.