ArticlePain2019
The paracetamol metabolite N-acetylp-benzoquinone imine reduces excitability in first- and second-order neurons of the pain pathway through actions on KV7 channels.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed, 34 citations in OpenAlex.
- Could NAPQI Contribute to Paracetamol Analgesia? Redox Modulation of Kv7 Ion Channels.Pharmacology research & perspectives · 2026Review
- Insights into ion channels to identify drug target for neuropathic pain management.Inflammopharmacology · 2025Review
- GPR88 promotes neurite outgrowth of sensory neurons via activation of GFrontiers in pharmacology · 2025Article
- Gaussian white noise stimulation as an alternative method to excite sensory neurons.Frontiers in pharmacology · 2025Article
- Combining clinically common drugs with hindlimb stretching in spinal cord injured rodents.Spinal cord · 2024Article
- The pharmacology activities ofHeliyon · 2024Review
- Analgesic Action of Acetaminophen via Kv7 Channels.International journal of molecular sciences · 2022Article
- Mechanisms of sympathoexcitationFrontiers in pharmacology · 2022Article
- DecipheringFrontiers in cellular neuroscience · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action.Temperature (Austin, Tex.) · 2021Review
- The M-current works in tandem with the persistent sodium current to set the speed of locomotion.PLoS biology · 2020Article
- Novel Analgesics with Peripheral Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Nociceptor Signalling through ion Channel Regulation via GPCRs.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paracetamol (acetaminophen, APAP) is one of the most frequently used analgesic agents worldwide. It is generally preferred over nonsteroidal anti-inflammatory drugs because it does not cause typical adverse effects resulting from the inhibition of cyclooxygenases, such as gastric ulcers. Nevertheless, inhibitory impact on these enzymes is claimed to contribute to paracetamols mechanisms of action which, therefore, remained controversial. Recently, the APAP metabolites N-arachidonoylaminophenol (AM404) and N-acetyl-p-benzoquinone imine (NAPQI) have been detected in the central nervous system after systemic APAP administration and were reported to mediate paracetamol effects. In contrast to nonsteroidal anti-inflammatory drugs that rather support seizure activity, paracetamol provides anticonvulsant actions, and this dampening of neuronal activity may also form the basis for analgesic effects. Here, we reveal that the APAP metabolite NAPQI, but neither the parent compound nor the metabolite AM404, reduces membrane excitability in rat dorsal root ganglion (DRG) and spinal dorsal horn (SDH) neurons. The observed reduction of spike frequencies is accompanied by hyperpolarization in both sets of neurons. In parallel, NAPQI, but neither APAP nor AM404, increases currents through KV7 channels in DRG and SDH neurons, and the impact on neuronal excitability is absent if KV7 channels are blocked. Furthermore, NAPQI can revert the inhibitory action of the inflammatory mediator bradykinin on KV7 channels but does not affect synaptic transmission between DRG and SDH neurons. These results show that the paracetamol metabolite NAPQI dampens excitability of first- and second-order neurons of the pain pathway through an action on KV7 channels.
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.