{"id":"a8605f1d-404f-5055-8dc2-d6a2e857ec9b","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-trpm8-skin-delivery-requirement","predicate":"determines","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f23faa92-7fb9-5bb3-821b-30a2da30ad22","mechanism_event_label":"The sensor only matters while the skin is actually cooling.","subject":{"id":"f9237e95-6a36-5f4b-89fc-4ee824f5f74a","slug":"skin-cooling-rate","display_name":"Rate of fall of skin temperature","entity_type_key":"cellular_process"},"object":{"id":"8d7989a0-37d9-5c72-84bb-29d7d4a5a932","slug":"core-temperature","display_name":"Core (rectal) body temperature","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f23faa92-7fb9-5bb3-821b-30a2da30ad22","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-trpm8-skin-delivery-requirement-event","event_type":"biochemical_relationship","label":"The sensor only matters while the skin is actually cooling.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3a3a699e-3d5b-528c-89d6-62dc302e4dc6","slug":"m8-b","display_name":"M8-B, a selective TRPM8 antagonist","entity_type_key":"small_molecule"},"role":"probe_antagonist","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f9237e95-6a36-5f4b-89fc-4ee824f5f74a","slug":"skin-cooling-rate","display_name":"Rate of fall of skin temperature","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8d7989a0-37d9-5c72-84bb-29d7d4a5a932","slug":"core-temperature","display_name":"Core (rectal) body temperature","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rats and mice with a selective TRPM8 antagonist given by several routes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"M8-B intravenously, intrathecally or intracerebroventricularly, at constant or changing ambient temperature","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cold-water-immersion","display_name":"Cold water immersion","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat, mouse and human channels in vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The sensor only matters while the skin is actually cooling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cold-p22323721] Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. 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The peripheral site of action is inferred from route comparison, not from direct measurement at the nerve ending.\nexposure: M8-B intravenously, intrathecally or intracerebroventricularly, at constant or changing ambient temperature\nevidence_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\"}\n[cold-p22323721] Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. 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