M8-B, a selective TRPM8 antagonist: molecular mechanisms & dependencies

How nutrients influence it

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Human evidence only

How nutrients reach it in more than one step

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What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

M8-B decreased deep body temperature in Trpm8-positive mice and rats but not in Trpm8-null mice, and intravenous administration was more effective than intrathecal or intracerebroventricular, indicating a peripheral action.
M8-B, a selective TRPM8 antagonist → Core (rectal) body temperature source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/cold-research/22323721.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0", "start_char": 0, "end_char": 1784, "text_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0"}
experimental_model
Rats and mice with a selective TRPM8 antagonist given by several routes
exposure
M8-B intravenously, intrathecally or intracerebroventricularly, at constant or changing ambient temperature
limitations
On-target action is supported by the absence of effect in Trpm8-null mice. The peripheral site of action is inferred from route comparison, not from direct measurement at the nerve ending.
nutrient_topic
Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion
organism
Rat, mouse and human channels in vitro
plain_language
Blocking the skin cold sensor makes the body cool down, because it never learns it is cold.
primary_references
[cold-p22323721] Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. (2012). https://pubmed.ncbi.nlm.nih.gov/22323721/ DOI: 10.1523/jneurosci.5606-11.2012
tissue_or_cell_type
Skin sensory neurons and thermoeffectors
trigger_kind
machinery_impairment Imported condition classification; unverified.
Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 91–102
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats and mice with a selective TRPM8 antagonist given by several routes · source_derived_draft · unverified_draft
### cold-trpm8-blockade-temperature M8-B decreased deep body temperature in Trpm8-positive mice and rats but not in Trpm8-null mice, and intravenous administration was more effective than intrathecal or intracerebroventricular, indicating a peripheral action. Condition category: machinery_impairment nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Blocking the skin cold sensor makes the body cool down, because it never learns it is cold. organism: Rat, mouse and human channels in vitro tissue_or_cell_type: Skin sensory neurons and thermoeffectors experimental_model: Rats and mice with a selective TRPM8 antagonist given by several routes limitations: On-target action is supported by the absence of effect in Trpm8-null mice. The peripheral site of action is inferred from route comparison, not from direct measurement at the nerve ending. exposure: M8-B intravenously, intrathecally or intracerebroventricularly, at constant or changing ambient temperature evidence_span: {"source_cache": "artifacts/cold-research/22323721.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0", "start_char": 0, "end_char": 1784, "text_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0"} [cold-p22323721] Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. (2012). https://pubmed.ncbi.nlm.nih.gov/22323721/ DOI: 10.1523/jneurosci.5606-11.2012
Complete structured claim and evidence

Where it participates (unsigned role)

A low intravenous dose did not affect body temperature at a constantly high or constantly low ambient temperature, but readily decreased it when rats were kept warm during infusion and transferred to cold immediately after, and below 23 degrees C tail-skin temperature the effect was inversely related to skin temperature.
Rate of fall of skin temperature → Core (rectal) body temperature source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/cold-research/22323721.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0", "start_char": 0, "end_char": 1784, "text_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0"}
experimental_model
Rats and mice with a selective TRPM8 antagonist given by several routes
exposure
M8-B intravenously, intrathecally or intracerebroventricularly, at constant or changing ambient temperature
limitations
On-target action is supported by the absence of effect in Trpm8-null mice. The peripheral site of action is inferred from route comparison, not from direct measurement at the nerve ending.
nutrient_topic
Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion
organism
Rat, mouse and human channels in vitro
plain_language
The sensor only matters while the skin is actually cooling.
primary_references
[cold-p22323721] Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. (2012). https://pubmed.ncbi.nlm.nih.gov/22323721/ DOI: 10.1523/jneurosci.5606-11.2012
tissue_or_cell_type
Skin sensory neurons and thermoeffectors
Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 117–128
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats and mice with a selective TRPM8 antagonist given by several routes · source_derived_draft · unverified_draft
### cold-trpm8-skin-delivery-requirement A low intravenous dose did not affect body temperature at a constantly high or constantly low ambient temperature, but readily decreased it when rats were kept warm during infusion and transferred to cold immediately after, and below 23 degrees C tail-skin temperature the effect was inversely related to skin temperature. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The sensor only matters while the skin is actually cooling. organism: Rat, mouse and human channels in vitro tissue_or_cell_type: Skin sensory neurons and thermoeffectors experimental_model: Rats and mice with a selective TRPM8 antagonist given by several routes limitations: On-target action is supported by the absence of effect in Trpm8-null mice. The peripheral site of action is inferred from route comparison, not from direct measurement at the nerve ending. exposure: M8-B intravenously, intrathecally or intracerebroventricularly, at constant or changing ambient temperature evidence_span: {"source_cache": "artifacts/cold-research/22323721.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0", "start_char": 0, "end_char": 1784, "text_sha256": "c0ead3b0097eaa75bf74d806e7f40bc61da4275cdd0af92735be9cad681ed3f0"} [cold-p22323721] Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. (2012). https://pubmed.ncbi.nlm.nih.gov/22323721/ DOI: 10.1523/jneurosci.5606-11.2012
Complete structured claim and evidence

The events it takes part in

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Situations it appears in

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In the sources

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Open hypotheses

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This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

M8-B, a selective TRPM8 antagonist