Human transient receptor potential vanilloid 1 / TRPV1

dose

Cannabidiol or moringin with TRPV1, CB1 or CB2 antagonists

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

LPS-stimulated murine macrophages

limitations

The abstract does not establish direct binding of either compound to every tested receptor, and the result is not a clinical interaction.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

LPS-stimulated murine macrophages

plain_language

A TRPV1 antagonist impaired cannabidiol efficacy in the macrophage assay but did not alter moringin activity; CB1 and CB2 antagonists affected neither route.

primary_references

Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. (2016). https://pubmed.ncbi.nlm.nih.gov/27215129/ DOI: 10.1016/j.fitote.2016.05.008

route

In vitro perturbation

tissue

Receptor-antagonist separation of combination components

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 101–110

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · LPS-stimulated murine macrophages · source_derived_draft · unverified_draft

## moringa-cannabidiol-trpv1-separation A TRPV1 antagonist impaired cannabidiol efficacy in the macrophage assay but did not alter moringin activity; CB1 and CB2 antagonists affected neither route. Model/species: LPS-stimulated murine macrophages Tissue/system: Receptor-antagonist separation of combination components Exposure: Cannabidiol or moringin with TRPV1, CB1 or CB2 antagonists Route: In vitro perturbation Duration: Acute Limits: The abstract does not establish direct binding of either compound to every tested receptor, and the result is not a clinical interaction. Primary reference: Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. (2016). https://pubmed.ncbi.nlm.nih.gov/27215129/ DOI: 10.1016/j.fitote.2016.05.008 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/paracetamol-research/20862299.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2", "start_char": 0, "end_char": 1701, "text_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2"}

experimental_model

Formalin, tail immersion and von Frey tests in fatty acid amide hydrolase and TRPV1 knockout mice with intracerebroventricular injection

exposure

Oral acetaminophen at a dose lacking hypolocomotor activity, with intracerebroventricular AM404 and capsazepine

limitations

Two separate knockouts and a central antagonist all point the same way, and the dose was chosen to avoid sedation confounding the pain tests. Brain prostaglandin E2 was unchanged at that dose, which is a notable negative.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Mouse

plain_language

Remove the channel and the painkiller stops working, while putting the metabolite straight into the brain works.

primary_references

[apap-p20862299] TRPV1 in brain is involved in acetaminophen-induced antinociception. (2010). https://pubmed.ncbi.nlm.nih.gov/20862299/ DOI: 10.1371/journal.pone.0012748

tissue_or_cell_type

Brain

trigger_kind

machinery_impairment Imported condition classification; unverified.

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 311–322

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Formalin, tail immersion and von Frey tests in fatty acid amide hydrolase and TRPV1 knockout mice with intracerebroventricular injection · source_derived_draft · unverified_draft

### apap-analgesia-needs-trpv1 The antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity was absent in fatty acid amide hydrolase and TRPV1 knockout mice in the formalin, tail immersion and von Frey tests, that dose did not affect global brain contents of prostaglandin E2 or endocannabinoids, intracerebroventricular injection of AM404 produced a TRPV1-mediated antinociceptive effect in the formalin test, and pharmacological inhibition of brain TRPV1 by intracerebroventricular capsazepine abolished the antinociceptive effect of oral acetaminophen. Condition category: machinery_impairment nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Remove the channel and the painkiller stops working, while putting the metabolite straight into the brain works. organism: Mouse tissue_or_cell_type: Brain experimental_model: Formalin, tail immersion and von Frey tests in fatty acid amide hydrolase and TRPV1 knockout mice with intracerebroventricular injection limitations: Two separate knockouts and a central antagonist all point the same way, and the dose was chosen to avoid sedation confounding the pain tests. Brain prostaglandin E2 was unchanged at that dose, which is a notable negative. exposure: Oral acetaminophen at a dose lacking hypolocomotor activity, with intracerebroventricular AM404 and capsazepine evidence_span: {"source_cache": "artifacts/paracetamol-research/20862299.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2", "start_char": 0, "end_char": 1701, "text_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2"} [apap-p20862299] TRPV1 in brain is involved in acetaminophen-induced antinociception. (2010). https://pubmed.ncbi.nlm.nih.gov/20862299/ DOI: 10.1371/journal.pone.0012748

dose

Capsaicin-bound channel

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

TRPV1 structural model with site-specific functional tests

limitations

The study resolves a binding mechanism but does not specify human dietary pharmacokinetics.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

TRPV1 structural model with site-specific functional tests

plain_language

Capsaicin binds TRPV1 in a tail-up, head-down configuration and stabilizes the open state through vanillyl-group contact with the S4-S5 linker.

primary_references

Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel. (2015). https://pubmed.ncbi.nlm.nih.gov/26053297/ DOI: 10.1038/nchembio.1835

route

Structural and in-vitro mutational analysis

tissue

Ligand binding and channel opening

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 22–31

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1 structural model with site-specific functional tests · source_derived_draft · unverified_draft

## capsaicin-binding-pose Capsaicin binds TRPV1 in a tail-up, head-down configuration and stabilizes the open state through vanillyl-group contact with the S4-S5 linker. Model/species: TRPV1 structural model with site-specific functional tests Tissue/system: Ligand binding and channel opening Exposure: Capsaicin-bound channel Route: Structural and in-vitro mutational analysis Duration: Acute Limits: The study resolves a binding mechanism but does not specify human dietary pharmacokinetics. Primary reference: Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel. (2015). https://pubmed.ncbi.nlm.nih.gov/26053297/ DOI: 10.1038/nchembio.1835 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin concentration-response and noxious-range temperature

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cloned capsaicin receptor expressed from sensory-neuron cDNA

limitations

The cloned receptor experiment establishes channel gating, not the whole organism response to chili foods.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Cloned capsaicin receptor expressed from sensory-neuron cDNA

plain_language

Capsaicin activates TRPV1, a nonselective cation channel that is also activated by noxious heat.

primary_references

The capsaicin receptor: a heat-activated ion channel in the pain pathway. (1997). https://pubmed.ncbi.nlm.nih.gov/9349813/ DOI: 10.1038/39807

route

In vitro

tissue

Calcium influx and heat activation

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 11–20

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Cloned capsaicin receptor expressed from sensory-neuron cDNA · source_derived_draft · unverified_draft

## capsaicin-trpv1-gating Capsaicin activates TRPV1, a nonselective cation channel that is also activated by noxious heat. Model/species: Cloned capsaicin receptor expressed from sensory-neuron cDNA Tissue/system: Calcium influx and heat activation Exposure: Capsaicin concentration-response and noxious-range temperature Route: In vitro Duration: Acute Limits: The cloned receptor experiment establishes channel gating, not the whole organism response to chili foods. Primary reference: The capsaicin receptor: a heat-activated ion channel in the pain pathway. (1997). https://pubmed.ncbi.nlm.nih.gov/9349813/ DOI: 10.1038/39807 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Gamma-nonalactone 2.56 mM with a capsaicin concentration series

duration

Acute calcium response

evidence_access

Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRPV1-expressing HEK293 cells

limitations

Concentration-dependent mixed modulation; not a potent selective antagonist or established dietary interaction.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Human TRPV1-expressing HEK293 cells

plain_language

At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response.

primary_references

Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023

route

In vitro co-application

tissue

Capsaicin concentration-response assay

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 48–57

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1-expressing HEK293 cells · source_derived_draft · unverified_draft

## gamma-nonalactone-capsaicin-high At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response. Model/species: Human TRPV1-expressing HEK293 cells Tissue: Capsaicin concentration-response assay Exposure: Gamma-nonalactone 2.56 mM with a capsaicin concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Concentration-dependent mixed modulation; not a potent selective antagonist or established dietary interaction. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.

dose

Gamma-nonalactone 0.64 or 1.28 mM with a capsaicin concentration series

duration

Acute calcium response

evidence_access

Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRPV1-expressing HEK293 cells

limitations

Functional curve shifts do not directly locate a binding site. No human pungency or pain outcome was tested.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Human TRPV1-expressing HEK293 cells

plain_language

Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response.

primary_references

Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023

route

In vitro co-application

tissue

Capsaicin concentration-response assay

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 37–46

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1-expressing HEK293 cells · source_derived_draft · unverified_draft

## gamma-nonalactone-capsaicin-low Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response. Model/species: Human TRPV1-expressing HEK293 cells Tissue: Capsaicin concentration-response assay Exposure: Gamma-nonalactone 0.64 or 1.28 mM with a capsaicin concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Functional curve shifts do not directly locate a binding site. No human pungency or pain outcome was tested. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.

dose

Gamma-nonalactone 2 mM; six replicates; separate concentration-response series

duration

Acute fluorescence response; precise recording window not specified in accessed methods

evidence_access

Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells

limitations

Millimolar assay exposure is not dietary tissue exposure or clinical analgesia. Above 5 mM assay artifacts prevented reliable lactone EC50 fitting. Human receptor species confirmed in methods.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells

plain_language

Gamma-nonalactone evoked a calcium response in human-TRPV1-expressing HEK293 cells.

primary_references

Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023

route

In vitro bath addition

tissue

Fluo8 NW calcium-flux assay

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 15–24

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells · source_derived_draft · unverified_draft

## gamma-nonalactone-trpv1-activation Gamma-nonalactone evoked a calcium response in human-TRPV1-expressing HEK293 cells. Model/species: Human TRPV1 or TRPA1 stably expressed in Flp-In HEK293 cells Tissue: Fluo8 NW calcium-flux assay Exposure: Gamma-nonalactone 2 mM; six replicates; separate concentration-response series Route: In vitro bath addition Duration: Acute fluorescence response; precise recording window not specified in accessed methods Limits: Millimolar assay exposure is not dietary tissue exposure or clinical analgesia. Above 5 mM assay artifacts prevented reliable lactone EC50 fitting. Human receptor species confirmed in methods. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.

dose

Purified moringin

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRP-channel in-vitro assays

limitations

This selectivity result is assay-specific and does not exclude indirect effects on sensory signaling in vivo.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Human TRP-channel in-vitro assays

plain_language

In the same in-vitro comparison, moringin did not activate or only weakly activated TRPV1, TRPV2, TRPV3, TRPV4 and TRPM8 relative to its TRPA1 activity.

primary_references

Moringin, A Stable Isothiocyanate from Moringa oleifera, Activates the Somatosensory and Pain Receptor TRPA1 Channel In Vitro. (2020). https://pubmed.ncbi.nlm.nih.gov/32098328/ DOI: 10.3390/molecules25040976

route

In vitro

tissue

Channel selectivity panel

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 57–66

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human TRP-channel in-vitro assays · source_derived_draft · unverified_draft

## moringa-moringin-trp-selectivity In the same in-vitro comparison, moringin did not activate or only weakly activated TRPV1, TRPV2, TRPV3, TRPV4 and TRPM8 relative to its TRPA1 activity. Model/species: Human TRP-channel in-vitro assays Tissue/system: Channel selectivity panel Exposure: Purified moringin Route: In vitro Duration: Acute Limits: This selectivity result is assay-specific and does not exclude indirect effects on sensory signaling in vivo. Primary reference: Moringin, A Stable Isothiocyanate from Moringa oleifera, Activates the Somatosensory and Pain Receptor TRPA1 Channel In Vitro. (2020). https://pubmed.ncbi.nlm.nih.gov/32098328/ DOI: 10.3390/molecules25040976 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Eugenol alone or with QX-314

duration

Acute plus washout

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Rodent trigeminal-ganglion nociceptive neurons

limitations

Persistent cellular block is not a validated human dental regimen and may involve safety risks not tested here.

nutrient_topic

Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol

organism

Rodent trigeminal-ganglion nociceptive neurons

plain_language

Eugenol activated inward current in capsaicin-sensitive trigeminal neurons and, with QX-314, produced sodium-channel and action-potential block that persisted after washout.

primary_references

Co-Application of Eugenol and QX-314 Elicits the Prolonged Blockade of Voltage-Gated Sodium Channels in Nociceptive Trigeminal Ganglion Neurons. (2020). https://pubmed.ncbi.nlm.nih.gov/33167484/ DOI: 10.3390/biom10111513

route

In vitro co-application

tissue

TRPV1-associated entry, sodium current and action potentials

Eugenol: mechanism of action and interactions (2026-09-20) · lines 66–75

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Rodent trigeminal-ganglion nociceptive neurons · source_derived_draft · unverified_draft

## eugenol-trpv1-qx314 Eugenol activated inward current in capsaicin-sensitive trigeminal neurons and, with QX-314, produced sodium-channel and action-potential block that persisted after washout. Model/species: Rodent trigeminal-ganglion nociceptive neurons Tissue/system: TRPV1-associated entry, sodium current and action potentials Exposure: Eugenol alone or with QX-314 Route: In vitro co-application Duration: Acute plus washout Limits: Persistent cellular block is not a validated human dental regimen and may involve safety risks not tested here. Primary reference: Co-Application of Eugenol and QX-314 Elicits the Prolonged Blockade of Voltage-Gated Sodium Channels in Nociceptive Trigeminal Ganglion Neurons. (2020). https://pubmed.ncbi.nlm.nih.gov/33167484/ DOI: 10.3390/biom10111513 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Repeated capsaicin; calcineurin inhibitor, forskolin and point mutants

duration

Acute repeated activation

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

TRPV1-transfected HEK293T or HeLa cells

limitations

Kinase and phosphatase manipulations identify regulatory machinery in engineered cells, not a dietary calcium threshold.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

TRPV1-transfected HEK293T or HeLa cells

plain_language

Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370.

primary_references

Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. (2005). https://pubmed.ncbi.nlm.nih.gov/15691846/ DOI: 10.1074/jbc.M410917200

route

In vitro

tissue

Whole-cell capsaicin currents

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 33–42

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1-transfected HEK293T or HeLa cells · source_derived_draft · unverified_draft

## capsaicin-calcineurin-desensitization Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370. Model/species: TRPV1-transfected HEK293T or HeLa cells Tissue/system: Whole-cell capsaicin currents Exposure: Repeated capsaicin; calcineurin inhibitor, forskolin and point mutants Route: In vitro Duration: Acute repeated activation Limits: Kinase and phosphatase manipulations identify regulatory machinery in engineered cells, not a dietary calcium threshold. Primary reference: Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. (2005). https://pubmed.ncbi.nlm.nih.gov/15691846/ DOI: 10.1074/jbc.M410917200 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin with capsazepine or cyclosporine controls

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Primary cardiomyocytes; rat reperfusion model for downstream peptide work

limitations

The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Primary cardiomyocytes; rat reperfusion model for downstream peptide work

plain_language

Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect.

primary_references

Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774

route

In vitro

tissue

Mitochondrial TRPV1 and membrane potential

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary cardiomyocytes; rat reperfusion model for downstream peptide work · source_derived_draft · unverified_draft

## capsaicin-cardiomyocyte-mitochondria Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect. Model/species: Primary cardiomyocytes; rat reperfusion model for downstream peptide work Tissue/system: Mitochondrial TRPV1 and membrane potential Exposure: Capsaicin with capsazepine or cyclosporine controls Route: In vitro Duration: Acute Limits: The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result. Primary reference: Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

6 ppm capsaicin rinse twice daily

duration

Days 3-17

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Healthy human volunteers

limitations

Reduced sensation was not explained by TRPV1 transcript abundance; protein trafficking and neural adaptation were not resolved.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Healthy human volunteers

plain_language

Twice-daily 6 ppm capsaicin rinses reduced oral capsaicin burn over 17 days without a detected decrease in fungiform-papilla TRPV1 mRNA.

primary_references

Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers. (2024). https://pubmed.ncbi.nlm.nih.gov/38135109/ DOI: 10.1016/j.physbeh.2023.114447

route

Oral rinse

tissue

Oral sensory ratings and fungiform-papilla TRPV1 expression

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 66–75

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Healthy human volunteers · source_derived_draft · unverified_draft

## capsaicin-human-oral-desensitization Twice-daily 6 ppm capsaicin rinses reduced oral capsaicin burn over 17 days without a detected decrease in fungiform-papilla TRPV1 mRNA. Model/species: Healthy human volunteers Tissue/system: Oral sensory ratings and fungiform-papilla TRPV1 expression Exposure: 6 ppm capsaicin rinse twice daily Route: Oral rinse Duration: Days 3-17 Limits: Reduced sensation was not explained by TRPV1 transcript abundance; protein trafficking and neural adaptation were not resolved. Primary reference: Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers. (2024). https://pubmed.ncbi.nlm.nih.gov/38135109/ DOI: 10.1016/j.physbeh.2023.114447 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Prolonged capsaicin followed by lipid-kinase blockade

duration

Recovery interval

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

TRPV1-expressing cells with Kir2.1 PIP2 biosensor

limitations

High intracellular ATP and PIP2 resynthesis were required; this is an experimental machinery perturbation, not evidence that dietary ATP supplementation changes analgesia.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

TRPV1-expressing cells with Kir2.1 PIP2 biosensor

plain_language

Blocking phosphatidylinositol-4-kinase prevented recovery of TRPV1 after prolonged capsaicin desensitization, linking recovery to PIP2 resynthesis.

primary_references

Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. (2005). https://pubmed.ncbi.nlm.nih.gov/15888659/ DOI: 10.1523/JNEUROSCI.1296-05.2005

route

In vitro

tissue

Channel recovery after desensitization

trigger_kind

machinery_impairment Imported condition classification; unverified.

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 44–53

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1-expressing cells with Kir2.1 PIP2 biosensor · source_derived_draft · unverified_draft

## capsaicin-pip2-recovery Blocking phosphatidylinositol-4-kinase prevented recovery of TRPV1 after prolonged capsaicin desensitization, linking recovery to PIP2 resynthesis. Model/species: TRPV1-expressing cells with Kir2.1 PIP2 biosensor Tissue/system: Channel recovery after desensitization Exposure: Prolonged capsaicin followed by lipid-kinase blockade Route: In vitro Duration: Recovery interval Limits: High intracellular ATP and PIP2 resynthesis were required; this is an experimental machinery perturbation, not evidence that dietary ATP supplementation changes analgesia. Primary reference: Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. (2005). https://pubmed.ncbi.nlm.nih.gov/15888659/ DOI: 10.1523/JNEUROSCI.1296-05.2005 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin or piperine concentration-response; second exposure; SB366791 control

duration

Acute sequential exposure

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human PC-3 cells expressing TRPV1

limitations

Comparable assay behavior does not establish equivalent potency, oral exposure, or benefit in humans.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Human PC-3 cells expressing TRPV1

plain_language

Piperine and capsaicin both stimulated TRPV1-dependent calcium responses in human PC-3 cells and both showed reduced responses on second exposure.

primary_references

Pharmacodynamics of TRPV1 agonists in a bioassay using human PC-3 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24688365/ DOI: 10.1155/2014/184526

route

In vitro

tissue

Fluo-4 calcium-response bioassay

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 110–119

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human PC-3 cells expressing TRPV1 · source_derived_draft · unverified_draft

## capsaicin-piperine-shared-trpv1 Piperine and capsaicin both stimulated TRPV1-dependent calcium responses in human PC-3 cells and both showed reduced responses on second exposure. Model/species: Human PC-3 cells expressing TRPV1 Tissue/system: Fluo-4 calcium-response bioassay Exposure: Capsaicin or piperine concentration-response; second exposure; SB366791 control Route: In vitro Duration: Acute sequential exposure Limits: Comparable assay behavior does not establish equivalent potency, oral exposure, or benefit in humans. Primary reference: Pharmacodynamics of TRPV1 agonists in a bioassay using human PC-3 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24688365/ DOI: 10.1155/2014/184526 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin followed by mustard oil/TRPA1 stimulation

duration

Acute sequential exposure

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Sensory neurons and heterologous channel expression

limitations

The mechanism differed from mustard-oil homologous desensitization and was not regulated by calcineurin in this study.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Sensory neurons and heterologous channel expression

plain_language

Capsaicin cross-desensitized TRPA1 through a calcium-dependent route associated with PLC activation and PIP2 depletion.

primary_references

Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. (2007). https://pubmed.ncbi.nlm.nih.gov/17584831/ DOI: 10.1113/jphysiol.2007.133231

route

In vitro

tissue

TRPA1 responses after TRPV1 agonism

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 55–64

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Sensory neurons and heterologous channel expression · source_derived_draft · unverified_draft

## capsaicin-trpa1-cross-desensitization Capsaicin cross-desensitized TRPA1 through a calcium-dependent route associated with PLC activation and PIP2 depletion. Model/species: Sensory neurons and heterologous channel expression Tissue/system: TRPA1 responses after TRPV1 agonism Exposure: Capsaicin followed by mustard oil/TRPA1 stimulation Route: In vitro Duration: Acute sequential exposure Limits: The mechanism differed from mustard-oil homologous desensitization and was not regulated by calcineurin in this study. Primary reference: Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. (2007). https://pubmed.ncbi.nlm.nih.gov/17584831/ DOI: 10.1113/jphysiol.2007.133231 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_span

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experimental_model

Cerebrospinal fluid and blood sampled from 26 adult male patients after intravenous paracetamol

exposure

1 gram intravenous paracetamol, with AM404 measured by liquid chromatography-tandem mass spectrometry

limitations

The first human demonstration that the metabolite reaches the central nervous system, and simultaneously the strongest quantitative objection to its importance, since the concentrations found are far below the reported potency of the compound.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Human

plain_language

The metabolite really is in human brain fluid, at about a thousandth of the concentration it is thought to need.

primary_references

[apap-p29238213] First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid. (2017). https://pubmed.ncbi.nlm.nih.gov/29238213/ DOI: 10.2147/jpr.s143500

tissue_or_cell_type

Cerebrospinal fluid

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 363–374

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cerebrospinal fluid and blood sampled from 26 adult male patients after intravenous paracetamol · source_derived_draft · unverified_draft

### apap-am404-in-human-csf-but-low Cerebrospinal fluid and blood were collected from 26 adult male patients between 10 and 211 minutes after intravenous administration of 1 gram of paracetamol, AM404 was detected in 17 of the 26 evaluable cerebrospinal fluid samples at 5 to 40 nanomoles per litre and paracetamol was measurable within 10 minutes with a maximum measured concentration of 60 micromoles per litre at 206 minutes, the first report of AM404 in human cerebrospinal fluid after paracetamol, although the measured concentrations were far below the previously documented half-maximal inhibitory concentration for this metabolite. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The metabolite really is in human brain fluid, at about a thousandth of the concentration it is thought to need. organism: Human tissue_or_cell_type: Cerebrospinal fluid experimental_model: Cerebrospinal fluid and blood sampled from 26 adult male patients after intravenous paracetamol limitations: The first human demonstration that the metabolite reaches the central nervous system, and simultaneously the strongest quantitative objection to its importance, since the concentrations found are far below the reported potency of the compound. exposure: 1 gram intravenous paracetamol, with AM404 measured by liquid chromatography-tandem mass spectrometry evidence_span: {"source_cache": "artifacts/paracetamol-research/29238213.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f8c752d7c1931585f2ce5bc6059b45b103e73fbc7e067912b0d2c60e8541165", "start_char": 0, "end_char": 1557, "text_sha256": "3f8c752d7c1931585f2ce5bc6059b45b103e73fbc7e067912b0d2c60e8541165"} [apap-p29238213] First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid. (2017). https://pubmed.ncbi.nlm.nih.gov/29238213/ DOI: 10.2147/jpr.s143500

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/paracetamol-research/15987694.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8da7599ee6674ced34346ae03fae0e421bcc5c1f53b0cb879145d7a511502001", "start_char": 0, "end_char": 1093, "text_sha256": "8da7599ee6674ced34346ae03fae0e421bcc5c1f53b0cb879145d7a511502001"}

experimental_model

Brain and spinal cord metabolite identification in wild-type and fatty acid amide hydrolase knockout mice

exposure

Acetaminophen, with the conjugation step tested by genetic deletion of the conjugating enzyme

limitations

Identifies a previously unknown route of drug metabolism and proves the enzyme by knockout. The downstream activities are measured on purified enzyme and cell lines rather than in the treated animal.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Mouse

plain_language

The brain takes the drug apart and builds the pieces into something new, and that something is what acts.

primary_references

[apap-p15987694] Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. (2005). https://pubmed.ncbi.nlm.nih.gov/15987694/ DOI: 10.1074/jbc.m501489200

tissue_or_cell_type

Brain and spinal cord

trigger_kind

machinery_impairment Imported condition classification; unverified.

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 298–309

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Brain and spinal cord metabolite identification in wild-type and fatty acid amide hydrolase knockout mice · source_derived_draft · unverified_draft

### apap-faah-builds-am404 Acetaminophen, following deacetylation to its primary amine, is conjugated with arachidonic acid in the brain and the spinal cord to form the potent TRPV1 agonist N-arachidonoylphenolamine, and this conjugation is absent in mice lacking the enzyme fatty acid amide hydrolase; AM404 also inhibits purified cyclooxygenase-1 and -2 and prostaglandin synthesis in lipopolysaccharide-stimulated macrophages and acts on the endogenous cannabinoid system, identifying fatty acid conjugation as a novel pathway for drug metabolism. Condition category: machinery_impairment nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The brain takes the drug apart and builds the pieces into something new, and that something is what acts. organism: Mouse tissue_or_cell_type: Brain and spinal cord experimental_model: Brain and spinal cord metabolite identification in wild-type and fatty acid amide hydrolase knockout mice limitations: Identifies a previously unknown route of drug metabolism and proves the enzyme by knockout. The downstream activities are measured on purified enzyme and cell lines rather than in the treated animal. exposure: Acetaminophen, with the conjugation step tested by genetic deletion of the conjugating enzyme evidence_span: {"source_cache": "artifacts/paracetamol-research/15987694.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8da7599ee6674ced34346ae03fae0e421bcc5c1f53b0cb879145d7a511502001", "start_char": 0, "end_char": 1093, "text_sha256": "8da7599ee6674ced34346ae03fae0e421bcc5c1f53b0cb879145d7a511502001"} [apap-p15987694] Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system. (2005). https://pubmed.ncbi.nlm.nih.gov/15987694/ DOI: 10.1074/jbc.m501489200

evidence_span

{"source_cache": "artifacts/paracetamol-research/21628499.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "784e57af3594f8d46b3b9fa70cdbc69451f9c2d424253c3b69b216d7cc541613", "start_char": 0, "end_char": 1809, "text_sha256": "784e57af3594f8d46b3b9fa70cdbc69451f9c2d424253c3b69b216d7cc541613"}

experimental_model

Body temperature after paracetamol in cannabinoid receptor 1 and TRPV1 knockout mice with antagonists and fatty acid amide hydrolase manipulation

exposure

300 milligrams per kilogram paracetamol in knockouts and after AM251 or SB366791, with AM404 given directly

limitations

Applies the same knockout logic used for analgesia to a different endpoint and gets the opposite answer, which is why both are recorded. Hypothermia below normal is not the same endpoint as antipyresis in fever.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Mouse

plain_language

The same knockouts that abolish the painkilling leave the temperature drop completely untouched.

primary_references

[apap-p21628499] Paracetamol-induced hypothermia is independent of cannabinoids and transient receptor potential vanilloid-1 and is not mediated by AM404. (2011). https://pubmed.ncbi.nlm.nih.gov/21628499/ DOI: 10.1124/dmd.111.038638

tissue_or_cell_type

Whole body temperature

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 376–387

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Body temperature after paracetamol in cannabinoid receptor 1 and TRPV1 knockout mice with antagonists and fatty acid amide hydrolase manipulation · source_derived_draft · unverified_draft

### apap-hypothermia-is-a-different-mechanism Paracetamol induced hypothermia to the same extent in cannabinoid receptor 1 and TRPV1 knockout mice as in wild-type mice and to the same extent in mice pretreated with the antagonists AM251 or SB366791 as in controls, AM404 failed to induce hypothermia at pharmacological doses, inhibition of fatty acid amide hydrolase did not prevent the development of hypothermia and paracetamol induced hypothermia in fatty acid amide hydrolase knockout mice to the same extent as in wild-type mice, so paracetamol induces hypothermia independent of cannabinoids and TRPV1 and AM404 does not mediate this response. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The same knockouts that abolish the painkilling leave the temperature drop completely untouched. organism: Mouse tissue_or_cell_type: Whole body temperature experimental_model: Body temperature after paracetamol in cannabinoid receptor 1 and TRPV1 knockout mice with antagonists and fatty acid amide hydrolase manipulation limitations: Applies the same knockout logic used for analgesia to a different endpoint and gets the opposite answer, which is why both are recorded. Hypothermia below normal is not the same endpoint as antipyresis in fever. exposure: 300 milligrams per kilogram paracetamol in knockouts and after AM251 or SB366791, with AM404 given directly evidence_span: {"source_cache": "artifacts/paracetamol-research/21628499.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "784e57af3594f8d46b3b9fa70cdbc69451f9c2d424253c3b69b216d7cc541613", "start_char": 0, "end_char": 1809, "text_sha256": "784e57af3594f8d46b3b9fa70cdbc69451f9c2d424253c3b69b216d7cc541613"} [apap-p21628499] Paracetamol-induced hypothermia is independent of cannabinoids and transient receptor potential vanilloid-1 and is not mediated by AM404. (2011). https://pubmed.ncbi.nlm.nih.gov/21628499/ DOI: 10.1124/dmd.111.038638

evidence_span

{"source_cache": "artifacts/paracetamol-research/23940628.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cc9d85547497bfdf88095aaeccf5a11cb9198140ebb35523d5da1b85f76e0a44", "start_char": 0, "end_char": 2208, "text_sha256": "cc9d85547497bfdf88095aaeccf5a11cb9198140ebb35523d5da1b85f76e0a44"}

experimental_model

Metabolite formation and antinociception for 4-aminophenol and a vanillylamine analogue across knockouts and pharmacological blockade

exposure

Systemic 4-aminophenol and 4-hydroxy-3-methoxybenzylamine, with fatty acid amide hydrolase, TRPV1, cannabinoid and serotonergic manipulations

limitations

The broadest test of the route: it reconstructs the whole chain from metabolite formation to descending pathway, and shows the profile of the metabolite matches that of the parent drug.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Mouse and rat

plain_language

Every step of the proposed chain was cut in turn, and cutting any of them stopped the painkilling.

primary_references

[apap-p23940628] Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain. (2013). https://pubmed.ncbi.nlm.nih.gov/23940628/ DOI: 10.1371/journal.pone.0070690

tissue_or_cell_type

Brain and spinal cord

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 324–335

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolite formation and antinociception for 4-aminophenol and a vanillylamine analogue across knockouts and pharmacological blockade · source_derived_draft · unverified_draft

### apap-the-whole-chain Systemic 4-aminophenol and 4-hydroxy-3-methoxybenzylamine led to dose-dependent formation of AM404 and of arvanil and olvanil respectively in the mouse brain, the order of potency of these lipid metabolites as TRPV1 activators being arvanil equal to olvanil much greater than AM404, both parent amines displayed antinociceptive activity in rodent pain tests, formation of these metabolites and the antinociceptive effects were substantially reduced or disappeared in fatty acid amide hydrolase null mice, activity was lost in TRPV1 null mice, intracerebroventricular capsazepine eliminated the effects, and in the rat, inhibition of fatty acid amide hydrolase, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors and chemical deletion of bulbospinal serotonergic pathways all prevented the action, giving a pharmacological profile identical to that previously reported for paracetamol. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Every step of the proposed chain was cut in turn, and cutting any of them stopped the painkilling. organism: Mouse and rat tissue_or_cell_type: Brain and spinal cord experimental_model: Metabolite formation and antinociception for 4-aminophenol and a vanillylamine analogue across knockouts and pharmacological blockade limitations: The broadest test of the route: it reconstructs the whole chain from metabolite formation to descending pathway, and shows the profile of the metabolite matches that of the parent drug. exposure: Systemic 4-aminophenol and 4-hydroxy-3-methoxybenzylamine, with fatty acid amide hydrolase, TRPV1, cannabinoid and serotonergic manipulations evidence_span: {"source_cache": "artifacts/paracetamol-research/23940628.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cc9d85547497bfdf88095aaeccf5a11cb9198140ebb35523d5da1b85f76e0a44", "start_char": 0, "end_char": 2208, "text_sha256": "cc9d85547497bfdf88095aaeccf5a11cb9198140ebb35523d5da1b85f76e0a44"} [apap-p23940628] Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain. (2013). https://pubmed.ncbi.nlm.nih.gov/23940628/ DOI: 10.1371/journal.pone.0070690

dose

Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar

duration

Acute fluorescence assay

evidence_access

Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRPV1 or TRPA1 expressed in HEK293 cells

limitations

Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Human TRPV1 or TRPA1 expressed in HEK293 cells

plain_language

Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response.

primary_references

Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023

route

In vitro co-exposure

tissue

Receptor antagonist controls

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 70–79

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 expressed in HEK293 cells · source_derived_draft · unverified_draft

## gamma-nonalactone-capsazepine-control Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response. Model/species: Human TRPV1 or TRPA1 expressed in HEK293 cells Tissue: Receptor antagonist controls Exposure: Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar Route: In vitro co-exposure Duration: Acute fluorescence assay Limits: Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/23352977.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb", "start_char": 0, "end_char": 1707, "text_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb"}

experimental_model

Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method

exposure

Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine

limitations

An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Frog

plain_language

This block is not the famous receptor at work: blocking the receptor does not stop it, and a stronger agonist does not cause it.

primary_references

[dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011

tissue_or_cell_type

Sciatic nerve

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 127–138

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method · source_derived_draft · unverified_draft

### dhc-conduction-block-not-trpv1 Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the compound action potential, the TRPV1 antagonist capsazepine did not affect this activity, and the powerful TRPV1 agonist resiniferatoxin had no effect on compound action potentials, indicating no involvement of TRPV1 channels; capsaicin analogs and other vanilloids inhibited them in the same concentration-dependent way. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: This block is not the famous receptor at work: blocking the receptor does not stop it, and a stronger agonist does not cause it. organism: Frog tissue_or_cell_type: Sciatic nerve experimental_model: Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method limitations: An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds. exposure: Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/23352977.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb", "start_char": 0, "end_char": 1707, "text_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb"} [dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/42509404.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55ec938b5e2c0b1421c473c60c3468ad24770198ee9d1f6549c62af579bf4c4c", "start_char": 0, "end_char": 1925, "text_sha256": "55ec938b5e2c0b1421c473c60c3468ad24770198ee9d1f6549c62af579bf4c4c"}

experimental_model

Human gastric cancer cell lines NCI-N87 and HGC-27 with western blotting and TRPV1 knockdown rescue experiments

exposure

Dihydrocapsaicin at a range of concentrations, with TRPV1 expression interfered as the test of mediation

limitations

The knockdown rescue is the strength here. Note the unusual direction: the compound raised expression of its own receptor rather than merely activating it.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human cells

plain_language

It holds gastric cancer cells in place by pushing them back towards a settled, non-migrating state.

primary_references

[dhc-p42509404] Dihydrocapsaicin suppresses the migration and invasion of gastric cancer cells by upregulating TRPV1 expression. (2026). https://pubmed.ncbi.nlm.nih.gov/42509404/ DOI: 10.1007/s11626-026-01226-3

tissue_or_cell_type

Gastric cancer cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 725–736

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human gastric cancer cell lines NCI-N87 and HGC-27 with western blotting and TRPV1 knockdown rescue experiments · source_derived_draft · unverified_draft

### dhc-gastric-cancer-migration Dihydrocapsaicin significantly and dose-dependently inhibited the migration and invasion of gastric cancer cells NCI-N87 and HGC-27, significantly increased the expression of TRPV1 and E-cadherin proteins and inhibited the expression of N-cadherin, vimentin and Snail proteins, and functional rescue experiments confirmed that when TRPV1 expression was inhibited the inhibitory effect on migration and invasion was significantly weakened. Condition category: machinery_impairment nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It holds gastric cancer cells in place by pushing them back towards a settled, non-migrating state. organism: Human cells tissue_or_cell_type: Gastric cancer cells experimental_model: Human gastric cancer cell lines NCI-N87 and HGC-27 with western blotting and TRPV1 knockdown rescue experiments limitations: The knockdown rescue is the strength here. Note the unusual direction: the compound raised expression of its own receptor rather than merely activating it. exposure: Dihydrocapsaicin at a range of concentrations, with TRPV1 expression interfered as the test of mediation evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/42509404.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55ec938b5e2c0b1421c473c60c3468ad24770198ee9d1f6549c62af579bf4c4c", "start_char": 0, "end_char": 1925, "text_sha256": "55ec938b5e2c0b1421c473c60c3468ad24770198ee9d1f6549c62af579bf4c4c"} [dhc-p42509404] Dihydrocapsaicin suppresses the migration and invasion of gastric cancer cells by upregulating TRPV1 expression. (2026). https://pubmed.ncbi.nlm.nih.gov/42509404/ DOI: 10.1007/s11626-026-01226-3

evidence_span

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experimental_model

Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays

exposure

Dihydrocapsaicin against cardiopulmonary resuscitation alone and against body surface cooling

limitations

Proposes the central mechanism and measures each step, but with six animals per group and immunohistochemical rather than functional readouts.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The proposed route runs through the brain’s thermostat: calcium floods in and a hormone is released.

primary_references

[dhc-p29035676] The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29035676/ DOI: 10.1089/ther.2017.0032

tissue_or_cell_type

Hypothalamus, ventral septum and cerebral cortex

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 426–437

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays · source_derived_draft · unverified_draft

### dhc-hypothalamic-calcium-avp Hypothalamic TRPV1 expression, hypothalamic intracellular calcium concentration and arginine vasopressin concentration in the ventral septum were significantly higher in the dihydrocapsaicin group than in the control, resuscitation and body surface cooling groups, and the authors concluded that dihydrocapsaicin activates TRPV1 on hypothalamic cells to cause a large calcium influx which causes the release of vasopressin to induce hypothermia. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The proposed route runs through the brain’s thermostat: calcium floods in and a hormone is released. organism: Rat tissue_or_cell_type: Hypothalamus, ventral septum and cerebral cortex experimental_model: Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays limitations: Proposes the central mechanism and measures each step, but with six animals per group and immunohistochemical rather than functional readouts. exposure: Dihydrocapsaicin against cardiopulmonary resuscitation alone and against body surface cooling evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29035676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98", "start_char": 0, "end_char": 2035, "text_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98"} [dhc-p29035676] The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29035676/ DOI: 10.1089/ther.2017.0032

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion

exposure

Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm

limitations

The two control arms are what make this the strongest record here: the knockout shows the receptor is required, and the heat-support arm shows the temperature drop rather than receptor activation is what protects.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

The cooling happens through the receptor, and in these mice it barely touched the circulation.

primary_references

[dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. (2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013

tissue_or_cell_type

Brain and cardiovascular system

trigger_kind

machinery_impairment Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 296–307

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion · source_derived_draft · unverified_draft

### dhc-hypothermia-requires-trpv1 Dihydrocapsaicin at 1.25 mg/kg produced a stable drop in core temperature to 33 degrees in naive and ischaemia-reperfusion mice but not in TRPV1 knockout mice, and had no measurable effect on heart rate or cerebral perfusion while producing a slight transient drop in mean arterial pressure of less than 6 millimetres of mercury. Condition category: machinery_impairment nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The cooling happens through the receptor, and in these mice it barely touched the circulation. organism: Mouse tissue_or_cell_type: Brain and cardiovascular system experimental_model: Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion limitations: The two control arms are what make this the strongest record here: the knockout shows the receptor is required, and the heat-support arm shows the temperature drop rather than receptor activation is what protects. exposure: Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24305062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17", "start_char": 0, "end_char": 1711, "text_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17"} [dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. (2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013

evidence_span

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experimental_model

In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control

exposure

Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists

limitations

The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

The platelets were not simply being killed, and again the receptor is not the route.

primary_references

[dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

tissue_or_cell_type

Platelets

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 166–177

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control · source_derived_draft · unverified_draft

### dhc-platelet-effect-not-trpv1 Inhibition of aggregation was not due to direct toxicity of these agents towards platelets as judged by LDH release, and the TRPV1 antagonist SB-452533 did not affect inhibition of ADP-induced platelet aggregation by capsaicin and N-oleoyldopamine. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The platelets were not simply being killed, and again the receptor is not the route. organism: Human tissue_or_cell_type: Platelets experimental_model: In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control limitations: The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included. exposure: Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24953906.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717", "start_char": 0, "end_char": 1870, "text_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717"} [dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

evidence_span

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experimental_model

Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species

exposure

Continuous intravenous infusion of dihydrocapsaicin at 0.125 to 0.75 mg/kg/h in conscious animals

limitations

The reason dihydrocapsaicin rather than capsaicin is the agent used for this purpose: it was selected out of a screen. The calf arm matters because it is the only body mass here comparable to an adult human.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat, cynomolgus monkey and calf

plain_language

Out of a set of receptor agonists, this one gave the most controllable cooling, and the deeper the dose the deeper the drop.

primary_references

[dhc-p20932337] Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. (2010). https://pubmed.ncbi.nlm.nih.gov/20932337/ DOI: 10.1186/1471-2261-10-51

tissue_or_cell_type

Whole body

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 218–229

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species · source_derived_draft · unverified_draft

### dhc-selected-from-a-screen On screening a heterogeneous group of TRPV1 agonists in conscious rats, dihydrocapsaicin displayed a desirable hypothermic profile with regard to duration, depth and control, and in rats infusion at 0.125, 0.25, 0.50 and 0.75 mg/kg/h caused maximal temperature changes against vehicle of -0.9, -1.5, -2.0 and -4.2 degrees within about one hour until the six hour infusion was stopped, with dose-dependent immediate decreases also in cynomolgus monkeys. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Out of a set of receptor agonists, this one gave the most controllable cooling, and the deeper the dose the deeper the drop. organism: Rat, cynomolgus monkey and calf tissue_or_cell_type: Whole body experimental_model: Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species limitations: The reason dihydrocapsaicin rather than capsaicin is the agent used for this purpose: it was selected out of a screen. The calf arm matters because it is the only body mass here comparable to an adult human. exposure: Continuous intravenous infusion of dihydrocapsaicin at 0.125 to 0.75 mg/kg/h in conscious animals evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20932337.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "add9a23357b3b1d89126189d178c377e3b4934e1c047d4022cf4aa15fdfa6602", "start_char": 0, "end_char": 1847, "text_sha256": "add9a23357b3b1d89126189d178c377e3b4934e1c047d4022cf4aa15fdfa6602"} [dhc-p20932337] Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. (2010). https://pubmed.ncbi.nlm.nih.gov/20932337/ DOI: 10.1186/1471-2261-10-51

evidence_span

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experimental_model

Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels

exposure

Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9, N-VAMC10, olvanil, capsiate and vanillylamine on T-type channels

limitations

A second TRPV1-independent target, with a clear structural boundary: the ester analogue and the free amine do not do it. The channel work is in isolated preparations.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Sensory neuron preparations

plain_language

Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor.

primary_references

[dhc-p17362879] Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. (2007). https://pubmed.ncbi.nlm.nih.gov/17362879/ DOI: 10.1016/j.bbrc.2007.02.144

tissue_or_cell_type

Primary sensory neurons

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 140–151

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels · source_derived_draft · unverified_draft

### dhc-t-type-inhibition Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9 and N-VAMC10 directly and partially reversibly inhibited low-voltage-activated T-type calcium channels, whereas olvanil, capsiate and vanillylamine could not, and the capsaicin inhibition of T-type channels was independent of TRPV1 activation. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor. organism: Sensory neuron preparations tissue_or_cell_type: Primary sensory neurons experimental_model: Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels limitations: A second TRPV1-independent target, with a clear structural boundary: the ester analogue and the free amine do not do it. The channel work is in isolated preparations. exposure: Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9, N-VAMC10, olvanil, capsiate and vanillylamine on T-type channels evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/17362879.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201", "start_char": 0, "end_char": 1243, "text_sha256": "7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201"} [dhc-p17362879] Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. (2007). https://pubmed.ncbi.nlm.nih.gov/17362879/ DOI: 10.1016/j.bbrc.2007.02.144