{"id":"86b24921-b820-5303-80ea-e9232ecec8e7","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-hypothermia-requires-trpv1","predicate":"causes","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"b45ca5bb-6d2f-5711-8f77-1deb5e57cd40","mechanism_event_label":"The cooling happens through the receptor, and in these mice it barely touched the circulation.","subject":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"object":{"id":"9c65f451-6d72-547e-8b7a-b97fc57c270a","slug":"pharmacological-hypothermia","display_name":"Hypothermia induced by a drug rather than by physical cooling","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b45ca5bb-6d2f-5711-8f77-1deb5e57cd40","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-hypothermia-requires-trpv1-event","event_type":"biochemical_relationship","label":"The cooling happens through the receptor, and in these mice it barely touched the circulation.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8e0c61d8-3930-51d5-bce2-25a5edfb797c","slug":"human-trpv1","display_name":"Human transient receptor potential vanilloid 1 / TRPV1","entity_type_key":"protein"},"role":"required_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e1831ec2-adaa-50bd-85a1-84293b829cf5","slug":"mouse-trpv1-null","display_name":"Experimental TRPV1 knockout mouse genotype","entity_type_key":"protein_state"},"role":"test_genotype","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"631cc7e9-0d27-54c2-919b-009a569ca7b9","slug":"mean-arterial-pressure","display_name":"Mean arterial pressure","entity_type_key":"cellular_process"},"role":"co_measured","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5c2ca60f-0af2-5b25-b2ea-f75beda1f335","slug":"heart-rate","display_name":"Heart rate","entity_type_key":"cellular_process"},"role":"co_measured","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9c65f451-6d72-547e-8b7a-b97fc57c270a","slug":"pharmacological-hypothermia","display_name":"Hypothermia induced by a drug rather than by physical cooling","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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(2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Brain and cardiovascular system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"520f2f0f-2290-5044-b0d0-2c7c550188d9","evidence_kind":"source_excerpt","locator":"Lines 296-307","start_line":296,"end_line":307,"excerpt":"### dhc-hypothermia-requires-trpv1\nDihydrocapsaicin 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.\nCondition category: machinery_impairment\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: The cooling happens through the receptor, and in these mice it barely touched the circulation.\norganism: Mouse\ntissue_or_cell_type: Brain and cardiovascular system\nexperimental_model: Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion\nlimitations: 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.\nexposure: Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm\nevidence_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\"}\n[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","model_system":"Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. 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Not publisher full text.","file_path":"","sha256":"97d90ff5dc65dc321068c3e2a0525585f32b2e17eb0c6bfa0d9ef26dc2d6c5a3","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"395f1f43-d481-5016-a542-5ec8a619916e","title":"What does dihydrocapsaicin do to the circulation?","kind":"context_difference","status":"open","why":"Three records give three different answers. In conscious mice given 1.25 mg/kg subcutaneously there was no measurable effect on heart rate or cerebral perfusion and only a transient fall in mean arterial pressure of under 6 millimetres of mercury. In conscious rats given continuous intravenous infusion, mean arterial pressure rose by 25% and heart rate by 30% before high infusion rates produced episodes of bradycardia and hypotension. In anaesthetised rats given intravenous injection, heart rate fell while mean arterial pressure did not change. Species, route, dose, and whether the animal was conscious all differ between the three, and a bolus was separately shown to produce cardiovascular effects that an infusion did not. No single cardiovascular profile can be read off these records, which matters because the proposed clinical use is in people whose circulation is already unstable.","resolution":"Unresolved; needs review.","created_at":"2026-09-22 03:40:20","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/395f1f43-d481-5016-a542-5ec8a619916e","sides":[{"conflict_id":"395f1f43-d481-5016-a542-5ec8a619916e","ordinal":0,"label":"The cooling happens through the receptor, and in these mice it barely touched the circulation.","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","start_line":296,"end_line":307,"quote":"### dhc-hypothermia-requires-trpv1\nDihydrocapsaicin 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.\nCondition category: machinery_impairment\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: The cooling happens through the receptor, and in these mice it barely touched the circulation.\norganism: Mouse\ntissue_or_cell_type: Brain and cardiovascular system\nexperimental_model: Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion\nlimitations: 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.\nexposure: Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm\nevidence_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\"}\n[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","source_key":"import-c953cca8-774f-596d-b27a-f13c2c0b5fce","source_title":"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)","claim_ids":["86b24921-b820-5303-80ea-e9232ecec8e7"]},{"conflict_id":"395f1f43-d481-5016-a542-5ec8a619916e","ordinal":1,"label":"The first thing it does is push blood pressure and heart rate up, before anything else happens.","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","start_line":387,"end_line":398,"quote":"### dhc-initial-pressor-response\nCompared to baseline, infusion of dihydrocapsaicin caused an initial increase in mean arterial blood pressure of 25% in healthy rats and 10% in resuscitated rats, and an initial tachycardic response of 30% and 20% respectively.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: The first thing it does is push blood pressure and heart rate up, before anything else happens.\norganism: Rat\ntissue_or_cell_type: Cardiovascular system\nexperimental_model: Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment\nlimitations: The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal.\nexposure: Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/20807439.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c\", \"start_char\": 0, \"end_char\": 1709, \"text_sha256\": \"49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c\"}\n[dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39","source_key":"import-c953cca8-774f-596d-b27a-f13c2c0b5fce","source_title":"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)","claim_ids":["3b70f7f1-6aa3-51df-a56d-324c0645b1f5"]},{"conflict_id":"395f1f43-d481-5016-a542-5ec8a619916e","ordinal":2,"label":"It turns down the body’s own heater, which is part of why the temperature falls.","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","start_line":400,"end_line":411,"quote":"### dhc-shuts-down-brown-fat\nIntravenous injection of the TRPV1 agonist dihydrocapsaicin decreased brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature, expired carbon dioxide and heart rate, though not mean arterial pressure, during skin cooling in anaesthetised rats.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: It turns down the body’s own heater, which is part of why the temperature falls.\norganism: Rat\ntissue_or_cell_type: Nucleus tractus solitarius and brown adipose tissue\nexperimental_model: Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy\nlimitations: The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here.\nexposure: Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/29590555.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a\", \"start_char\": 0, \"end_char\": 1882, \"text_sha256\": \"947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a\"}\n[dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018","source_key":"import-c953cca8-774f-596d-b27a-f13c2c0b5fce","source_title":"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)","claim_ids":["c4275476-7f67-59cb-b369-cad042a0bb2b"]}]}],"corrections":[],"research":null}