{"id":"6439984d-5459-5ebe-bb5e-b71fc7f141d8","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:muscarinic-pain","predicate":"increases_in_recorded_comparison","statement":"Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"4f98112d-52da-5cf6-b2d4-e93edbf2b1f5","mechanism_event_label":"Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.","subject":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"object":{"id":"39f3f023-7999-5e8c-a147-ed5f7e71fd02","slug":"rodent-alcar-pain-threshold","display_name":"Rodent nociceptive threshold under ALCAR","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4f98112d-52da-5cf6-b2d4-e93edbf2b1f5","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:muscarinic-pain-event","event_type":"experimental_observation","label":"Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.","description":"### muscarinic-pain\n\nRepeated ALCAR increased pain thresholds in mouse and rat behavioral assays.\nAtropine, M1-selective antagonists, M1 antisense and hemicholinium-3 prevented the response. These experiments support indirect cholinergic involvement, not direct ALCAR agonism or clinical analgesic efficacy.\nModel and exposure: 100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. | 2002 | https://pubmed.ncbi.nlm.nih.gov/12504925/ | https://doi.org/10.1016/s0028-3908(02)00225-3 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"Repeated ALCAR","sequence_order":0,"notes":""},{"entity":{"id":"39f3f023-7999-5e8c-a147-ed5f7e71fd02","slug":"rodent-alcar-pain-threshold","display_name":"Rodent nociceptive threshold under ALCAR","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"increase","sequence_order":1,"notes":""},{"entity":{"id":"15f664ac-f08e-5c21-af61-f3961b3d8d4a","slug":"atropine","display_name":"Atropine, a muscarinic acetylcholine antagonist","entity_type_key":"chemical_species"},"role":"blocking drug","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5b9a10bd-37a3-58ae-9530-9f0d7ff02efc","slug":"hemicholinium-3","display_name":"Hemicholinium-3","entity_type_key":"small_molecule"},"role":"blocking choline-uptake inhibitor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c4a28f46-2ae2-5306-84cc-d6eaa20f25e0","slug":"rat-chrm1","display_name":"Rat muscarinic M1 receptor / Chrm1","entity_type_key":"protein"},"role":"implicated receptor","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"8e1d19fd-ad66-575d-81c4-9122f78915e5","slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"},"role":"uptake substrate","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"Repeated ALCAR\", \"comparator\": \"Control treatment\", \"endpoint\": \"Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.\", \"effect_direction\": \"increase\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. | https://pubmed.ncbi.nlm.nih.gov/12504925/ | https://doi.org/10.1016/s0028-3908(02)00225-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference muscarinic-pain; Atropine, M1-selective antagonists, M1 antisense and hemicholinium-3 prevented the response. These experiments support indirect cholinergic involvement, not direct ALCAR agonism or clinical analgesic efficacy.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"293aa189-35fb-5059-969f-cfa1fa2193ce","evidence_kind":"source_excerpt","locator":"Lines 164-170","start_line":164,"end_line":170,"excerpt":"### muscarinic-pain\n\nRepeated ALCAR increased pain thresholds in mouse and rat behavioral assays.\nAtropine, M1-selective antagonists, M1 antisense and hemicholinium-3 prevented the response. These experiments support indirect cholinergic involvement, not direct ALCAR agonism or clinical analgesic efficacy.\nModel and exposure: 100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. | 2002 | https://pubmed.ncbi.nlm.nih.gov/12504925/ | https://doi.org/10.1016/s0028-3908(02)00225-3 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.","model_system":"100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}