ArticleBritish journal of pharmacology2020
TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Two pore domain THIK2 potassium channels regulate acute and chronic pain signaling.Pain reports · 2026Article
- Gating shift to an ohmic mode of TREK-1 channel induced by docosahexaenoic acid.Biophysical journal · 2026Article
- KArchiv der Pharmazie · 2026Review
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Article
- Discovery of ONO-2920632 (VU6011887): A Highly Selective and CNS Penetrant TREK-2 (TWIK-Related K+ Channel 2) Preferring ActivatorACS chemical neuroscience · 2025Article
- Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation.Nature communications · 2024Article
- FXYD2 antisense oligonucleotide provides an efficient approach for long-lasting relief of chronic peripheral pain.JCI insight · 2023Article
- Transition between conformational states of the TREK-1 K2P channel promoted by interaction with PIPBiophysical journal · 2022Article
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- Translational value of non-human primates in opioid research.Experimental neurology · 2021Review
- The Prostacyclin Analogue, Treprostinil, Used in the Treatment of Pulmonary Arterial Hypertension, is a Potent Antagonist of TREK-1 and TREK-2 Potassium Channels.Frontiers in pharmacology · 2021Article
- CORRECTION.British journal of pharmacology · 2020Article
- TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects.British journal of pharmacology · 2020Article
Corrections and comments
- Erratum issuedCORRECTION.2020
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
background and purposeOpioids are effective painkillers. However, their risk-benefit ratio is dampened by numerous adverse effects and opioid misuse has led to a public health crisis. Safer alternatives are required, but isolating the antinociceptive effect of opioids from their adverse effects is a pharmacological challenge because activation of the μ opioid receptor triggers both the antinociceptive and adverse effects of opioids. EXPERIMENTAL APPROACH: The TREK1 potassium channel is activated downstream of μ receptor and involved in the antinociceptive activity of morphine but not in its adverse effects. Bypassing the μ opioid receptor to directly activate TREK1 could therefore be a safer analgesic strategy. KEY
resultsWe developed a selective TREK1 activator, RNE28, with antinociceptive activity in naive rodents and in models of inflammatory and neuropathic pain. This activity was lost in TREK1 knockout mice or wild-type mice treated with the TREK1 blocker spadin, showing that TREK1 is required for the antinociceptive activity of RNE28. RNE28 did not induce respiratory depression, constipation, rewarding effects, or sedation at the analgesic doses tested. CONCLUSION AND IMPLICATIONS: This proof-of-concept study shows that TREK1 activators could constitute a novel class of painkillers, inspired by the mechanism of action of opioids but devoid of their adverse effects.
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Registered trials
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.