Evidence map›Paper›PMID 38750093›Full record

ArticleScientific reports2024

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.

Hernan A Bazan, Surjyadipta Bhattacharjee, Madigan M Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A St Pierre, Neehar Desai, Patrick W Daly, Jessica A Cucinello-Ragland and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Convergent state-control of endogenous opioid analgesia.bioRxiv : the preprint server for biology · 2025
    Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Hernan A Bazan *Section of Vascular/Endovascular Surgery, Department of Surgery, Ochsner Clinic, New Orleans, LA, 70118, USA. hbazan@ochsner.org.
Surjyadipta Bhattacharjee *Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Madigan M ReidNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Bokkyoo JunNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Connor PolkNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Madeleine StrainNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Linsey A St PierreNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Neehar DesaiNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Patrick W DalyNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Jessica A Cucinello-RaglandDepartment of Physiology, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Scott EdwardsNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Javier RecioDepartment of Organic Chemistry and IQAR, University of Alcala, 28805, Alcala de Henares, Madrid, Spain.
Julio Alvarez-BuillaDepartment of Organic Chemistry and IQAR, University of Alcala, 28805, Alcala de Henares, Madrid, Spain.
James J CaiDepartment of Electrical and Computer Engineering, Texas A&M University, College Station, TX, 77843, USA.
Nicolas G BazanNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA. nbazan@lsuhsc.edu.

Funding

Novel non-narcotic analgesic for acute and chronic painR42NS119103 · NINDS · SOUTH RAMPART PHARMA, LLC · PI BAZAN, HERNAN A, BAZAN, NICOLAS G. · 2020 to 2022
$1.9M
NIH HHS 1R42NS119103-01A1NINDS NIH HHS R42 NS119103
6 · The paper itself

Abstract

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids' addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete Freund's adjuvant-induced inflammatory von Frey model. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception region, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways/networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH). Both regulate the expression of key genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptor 1 (CNR1), CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated Ca

Indexed as

AcetaminophenAnalgesicsArachidonic AcidsPeriaqueductal GrayTranscriptomeAmidohydrolasesAnimalsBenzoquinonesGlyceridesMaleMiceAcetaminophenAmidohydrolasesAnalgesicsArachidonic AcidsBenzoquinonesGlyceridesCNSLiver toxicityNon-opioidPhase 1 trialscRNA-seq

Identifiers

PMID38750093
PMCPMC11096368

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.