ArticleProceedings of the National Academy of Sciences of the United States of America2004
Peripheral analgesic blockade of hypernociception: activation of arginine/NO/cGMP/protein kinase G/ATP-sensitive K+ channel pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
- Activation of KFrontiers in physiology · 2025Pooled it
- Peripheral Analgesic Effect of a Novel Curcuminoid Derivative: Possible Involvement of Peripheral Opioid Receptor and ATP-Sensitive Potassium Ion Channel.Pharmaceutics · 2026Article
- Medicinal Plants That Modulate Nitric Oxide Synthase Activity: Implications in Inflammation and Oxidative Stress.Drug design, development and therapy · 2026Review
- Fructose-1,6-Bisphosphate Reduces Chronic Constriction Injury Neuropathic Pain in Mice by Targeting Dorsal Root Ganglia Nociceptive Neuron Activation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Nature's Remedies: Exploring the Potential of Propolis to Alleviate Non-Motor Manifestations of Parkinson's Disease.Molecules (Basel, Switzerland) · 2025Review
- Nicorandil antiallodynic activity in a model of neuropathic pain is associated with the activation of ATP-dependent potassium channels and opioidergic pathways, and reduced production of cytokines and neutrophils recruitment in paw, sciatic nerve, and dorsal root ganglia.Pharmacological reports : PR · 2024Article
- Kaurenoic Acid Reduces Ongoing Chronic Constriction Injury-Induced Neuropathic Pain: Nitric Oxide Silencing of Dorsal Root Ganglia Neurons.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Neuropathic ocular surface pain: Emerging drug targets and therapeutic implications.Expert opinion on therapeutic targets · 2022Review
- Flavonoids as Potential Anti-Inflammatory Molecules: A Review.Molecules (Basel, Switzerland) · 2022Review
- Article
- The Involvement of l-Arginine-Nitric Oxide-cGMP-ATP-Sensitive KMolecules (Basel, Switzerland) · 2021Article
- Review
- Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice.PloS one · 2021Article
- Antinociceptive effect of Lonchocarpus araripensis lectin: activation of L-arginine/NO/cGMP/KInflammopharmacology · 2020Article
- Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development.Molecules (Basel, Switzerland) · 2020Review
- Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway.Brain research · 2020Article
- The granulopoietic cytokine granulocyte colony-stimulating factor (G-CSF) induces pain: analgesia by rutin.Inflammopharmacology · 2019Article
- [Ru(bpy)Frontiers in pharmacology · 2019Article
- Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive KInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Chemical Biology of HChemical reviews · 2018Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The final step in the direct restoration of the nociceptor threshold by peripheral administration of morphine and dipyrone was recently suggested to result from the opening of ATP-sensitive K(+) channels (K(ATP)(+)). This channel is known to be open either directly by cGMP or indirectly via protein kinase G (PKG) stimulation. In the present study, it was shown that the blockade was caused by a specific PKG inhibitor (KT5823) of the antinociceptive effect of morphine and dipyrone on acute hypernociception and of dipyrone on persistent hypernociception. It was also shown that, in both models, KT5823 prevented the peripheral antinociceptive effect of an analogue of cGMP, the nitric oxide (NO) donor (S-nitroso-n-acetyl-d,l-penicilamine). However, in acute hypernociception, KT5823 did not prevent the peripheral antinociceptive effect of diazoxide (a direct K(ATP)(+) opener). In persistent hypernociception, the sensitization plateau was induced by daily injections of prostaglandin E(2) (PGE(2), 100 ng) into the rat paw for 14 days. After cessation of PGE(2) injections, the pharmacological blockade of persistent hypernociception led to a quiescent phase in which a rather small stimulus restored the hypernociceptive plateau. In this phase, glibenclamide (which specifically closes K(ATP)(+)) fully restored persistent hypernociception, as did injection of PGE(2). Thus, the activation of the arginine/NO/cGMP pathway causes direct blockade of acute and persistent hypernociception by opening K(ATP)(+) via the stimulation of PKG. Analgesic stimulators of the neuronal arginine/NO/cGMP/PKG/K(ATP)(+) pathway constitute a previously undescribed well defined class of peripheral analgesics with a mechanism of action different from either glucocorticoids or inhibitors of cyclooxygenases.
Indexed as
Identifiers
What OpenQuestion holds
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.