TRPV1 knockout mouse genotype: molecular mechanisms & dependencies

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What it does

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Recorded relationships

Where it participates (unsigned role)

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.
Human transient receptor potential vanilloid 1 / TRPV1 → Antinociception in thermal, mechanical and chemical pain tests source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
AM404 / N-arachidonoylphenolamine → Hypothermia induced by paracetamol below normal body temperature source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence

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Open hypotheses

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TRPV1 knockout mouse genotype