{"slug":"ara-290-carpal-tunnel","verification":{"valid":true,"entries":15,"head":"4217aa0c5436384adb1fdb9b3c80fd0a3d37566f7a8fd09319faafe8e22de9fe"},"count":15,"models":["grok/grok-4.3","grok-4.3","system/audit-repair","kimi/moonshot-v1-8k","gemini/gemini-2.5-flash","fill-slots"],"yield":{"passes":15,"energy_spent_rows":0,"total_cost_usd":0.010372,"waste_cost_usd":0,"total_tokens":17403,"material_outputs":9,"usd_per_output":0.001152,"models":[{"model":"kimi/moonshot-v1-8k","passes":2,"cost_usd":0.001121,"tokens_total":7476,"outputs":6,"waste_passes":0,"usd_per_output":0.000187},{"model":"gemini/gemini-2.5-flash","passes":1,"cost_usd":0.00037,"tokens_total":3567,"outputs":3,"waste_passes":0,"usd_per_output":0.000123},{"model":"grok-4.3","passes":3,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"system/audit-repair","passes":5,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"fill-slots","passes":2,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"grok/grok-4.3","passes":2,"cost_usd":0.008881,"tokens_total":6360,"outputs":0,"waste_passes":0,"usd_per_output":null}],"constraints":{"constitution":"/api/articles/constitution","collaborate_schema":"POST /api/protocol/collaborate","pricing_ppm":{"grok-4.3":[1.25,2.5],"grok/grok-4.3":[1.25,2.5],"grok-build-0.1":[1,2],"kimi/moonshot-v1-8k":[0.15,0.15],"gemini/gemini-2.5-flash":[0.075,0.3],"gemini/gemini-2.0-flash-lite":[0.075,0.3],"openai/gpt-4o":[2.5,10],"openai/gpt-4o-mini":[0.15,0.6],"system/reflex":[0,0],"ingest:deterministic":[0,0],"fill-slots":[0,0]}}},"contributions":[{"seq":0,"id":"k1","ts":"2026-06-29T08:54:07.101Z","model":"grok/grok-4.3","role":"writer","action":"redraft","payload":{"title":"ARA-290 for Carpal Tunnel: Human Trial Data on Nerve Symptoms and Fiber Density","register":"source_ledger","body":"## Background on Carpal Tunnel and Persistent Nerve Issues\n\nCarpal tunnel syndrome involves compression of the median nerve at the wrist. Even after surgical release, some patients experience ongoing sensory symptoms or incomplete functional recovery due to prior axonal damage.\n\n## ARA-290 Mechanism\n\nARA-290 is an 11-amino-acid peptide derived from erythropoietin that selectively activates the innate repair receptor (IRR). This activates anti-inflammatory and tissue-repair pathways without erythropoietic effects (human trial data; mechanistic).\n\n## Human Clinical Data\n\nIn a phase 2 double-blind placebo-controlled trial of 22 adults with type 2 diabetes and painful neuropathy, 4 mg ARA-290 subcutaneously daily for 28 days improved PainDetect neuropathic symptom scores by 3.3 points vs 1.1 for placebo at day 28 (p=0.037); improvement increased to 4.2 points at day 56 (human). Subgroup analysis of subjects with reduced corneal nerve fiber density showed +2.6 fibers/mm² increase vs +0.7 for placebo (p=0.02) (human).\n\nIn sarcoidosis-associated small-fiber neuropathy trials, ARA-290 improved neuropathic and autonomic symptoms and quality-of-life scores; one trial showed increased corneal nerve fiber abundance after 28 days (human).\n\nNo human trials have evaluated ARA-290 in carpal tunnel syndrome (human data absent).\n\n## Preclinical Data\n\nRat models of neuropathic pain demonstrated long-lasting relief after ARA-290, linked to reduced inflammation and axonal repair rather than analgesia (preclinical).\n\n## User Reports\n\nIsolated self-reports on forums describe symptom relief in small-fiber neuropathy after 4 mg daily protocols, with onset around day 12–13 and variable duration (anecdotal).\n\n## Evidence Summary\n\nHuman data exist for symptom improvement and limited nerve-fiber regrowth in diabetic and sarcoidosis neuropathies. No human data address carpal tunnel. All claims graded by available evidence tiers; no medical claims implied.","claims":[{"id":"c1","text":"In a phase 2 trial of T2D patients with neuropathy, 4 mg ARA-290 daily for 28 days improved PainDetect scores significantly vs placebo.","section":"Human Clinical Data","tier":"human","source_ids":["s1"],"source_status":"sourced","why_material":"Direct evidence of symptom improvement in human neuropathy trial","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c2","text":"Subgroup with low baseline corneal nerve density showed significant CNFD increase after ARA-290 vs placebo.","section":"Human Clinical Data","tier":"human","source_ids":["s1"],"source_status":"sourced","why_material":"Evidence of possible nerve fiber regrowth in humans","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c3","text":"No human trials of ARA-290 in carpal tunnel syndrome exist.","section":"Evidence Summary","tier":"human","source_ids":[],"source_status":"unsourced","why_material":"Clarifies absence of direct data for the target condition","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c4","text":"Rat models show ARA-290 produces long-lasting neuropathic pain relief via repair pathways.","section":"Preclinical Data","tier":"preclinical","source_ids":["s2"],"source_status":"sourced","why_material":"Separates animal from human evidence","evidence_basis":"derived_inference","weight":0.5,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}}],"sources":[{"id":"s1","type":"pubmed","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4365069/","title":"ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes","quote":"Neuropathic symptoms as assessed by the PainDetect questionnaire improved significantly in the ARA 290 group... In this group, a linear relationship existed between the observed change in CNFD and the change in symptoms... mean change in of +2.6 ± 1.0 fibers/mm² for ARA 290 (n = 18; p = 0.02)","link_status":"ok","quote_status":"unverified"},{"id":"s2","type":"review","url":"https://journals.lww.com/painrpts/fulltext/2016/08000/targeting_the_innate_repair_receptor_to_treat.2.aspx","title":"Targeting the innate repair receptor to treat neuropathy","quote":"Swartjes and colleagues... showed that ARA-290 produced long-lasting relief of neuropathic pain in rats","link_status":"ok","quote_status":"unverified"}]},"rationale":"","tokens_in":0,"tokens_out":0,"prev_hash":"genesis","hash":"1e822a0ea39b9a5414d5cc43e99de7b58c2578a14adedd2f7fa9f01eee91ec64"},{"seq":1,"id":"k2","ts":"2026-06-29T12:01:19.361Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s3","type":"reddit","url":"https://www.reddit.com/r/Biohackers/comments/1p2887b/anybody_try_ara290_peptide_for_nerve_damage/","title":"Anybody try ARA-290 peptide for nerve damage?","quote":"I also have tarsal tunnel syndrome, which is the ankle version of carpal tunnel syndrome; my tibial nerve is entrapped in scar tissue from a surgery. Because that nerve pain is caused by mechanical compression, I don't expect the peptide to help (and so far it has not).","link_status":"ok","quote_status":"unverified"},{"id":"s4","type":"reddit","url":"https://www.reddit.com/r/Biohackers/comments/1p2887b/anybody_try_ara290_peptide_for_nerve_damage/","title":"Anybody try ARA-290 peptide for nerve damage?","quote":"The boundaries of my nerve damage have shrunk several inches! In the first few weeks, it shrunk more than it had in the 6 months between the initial damage and when I started ARA-290. ... I am 100% certain that ARA-290 is responsible for my experience of several inches of recovery in mere weeks after the preceding 6 months of no improvement.","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"1e822a0ea39b9a5414d5cc43e99de7b58c2578a14adedd2f7fa9f01eee91ec64","hash":"3dd60d65206444ad349ed57994e5e2c0b2c04cab5b0ffecd325c9fbe89a84b92"},{"seq":2,"id":"k3","ts":"2026-06-29T12:06:47.513Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s5","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1o33123/peptide_ara290/","title":"Peptide ARA-290 : r/neuropathy","quote":"I titrated up 0.5 mg, 1 mg, 2 mg, 3 mg and finally 4 mg. At 3 and 4 milligrams I experienced painful pins and needles in my heels so I had to stop. ... I began last week at .5 mg, then 1, then 2, then 3 and finally 4 mg. I tittered slowly up due to my Sjogren's disease. I quickly developed painful tingling around the outside of both feet at 2 mg. Those last 3 days were very painful. ... I tried ARA290 last October and had to quit after 6 days.","link_status":"ok","quote_status":"unverified"},{"id":"s6","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1tvw5x6/ara290_disc_herniaton_nerve_pain/","title":"ARA-290 Disc Herniaton & Nerve Pain : r/neuropathy","quote":"Periphial neuropathy in hands/shoulder (emg showed carpal tunnel and medial nerve damage) feet and legs to lower back (3 fusions, lt knee replacement, rt hip replacement and waiting on rt knee replacement).","link_status":"ok","quote_status":"unverified"},{"id":"s7","type":"reddit","url":"https://www.reddit.com/r/tinnitus/comments/1papfky/anyone_try_ara290_peptide_for_this_tinnitus/","title":"Anyone try ARA290 peptide for this tinnitus? : r/tinnitus","quote":"It's a nerve healing peptide known to regenerate nerves like sciatica and carpal tunnel syndrome ...","link_status":"ok","quote_status":"unverified"},{"id":"s8","type":"x","url":"https://x.com/I_Research_Pept/status/2064434147792470183","title":"X post by @I_Research_Pept","quote":"Has anyone out there tried ARA-290? If so, what were you treating and what were the results? I never hear about this peptide, but want to try it for carpal tunnel. I purchased 7 vials from a vendor, but unfortunately, they were bad (floating clouds) and I have not repurchased yet","link_status":"ok","quote_status":"verified"},{"id":"s9","type":"x","url":"https://x.com/SEpilogueG/status/2049848962459513117","title":"X post by @SEpilogueG","quote":"Where do I buy these, specifically ARA-290? I have severe work induced carpal tunnel.","link_status":"ok","quote_status":"verified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"3dd60d65206444ad349ed57994e5e2c0b2c04cab5b0ffecd325c9fbe89a84b92","hash":"bfd24232c6022e409af9494ba50a5909d0f47817e6133b597ca72cb5096f5e58"},{"seq":3,"id":"k4","ts":"2026-06-29T12:46:57.407Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c12","tier":"system","text":"ARA-290 for Carpal Tunnel: Human Trial Data on Nerve Symptoms and Fiber Density is catalogued in this miscsubjects ledger as a tier-honest evidence graph (claims + hash-chained sources). This page summarizes what is claimed in the literature and online about the topic — not clinical recommendations.","who_claims":"miscsubjects protocol","source_ids":[],"slot":"what_it_is","posted_by":{"actor":"miscsubjects protocol","channel":"protocol/fill-slots","ts":"2026-06-29T12:46:57.407Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"bfd24232c6022e409af9494ba50a5909d0f47817e6133b597ca72cb5096f5e58","hash":"28a70b25582e8a7b4aee00e2a0fa682d2a62796747ea62d431227b02528c76f5"},{"seq":4,"id":"k5","ts":"2026-06-29T12:46:57.483Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c13","tier":"preclinical","text":"Per this ledger on ARA-290 for Carpal Tunnel: Human Trial Data on Nerve Symptoms and Fiber Density: 2 scientific and 7 anecdotal sources are catalogued; 2 preclinical claim(s) summarize animal/cell literature in-catalogue.","who_claims":"miscsubjects ledger synthesis","source_ids":[],"slot":"what_is_known","posted_by":{"actor":"miscsubjects ledger synthesis","channel":"protocol/fill-slots","ts":"2026-06-29T12:46:57.483Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"28a70b25582e8a7b4aee00e2a0fa682d2a62796747ea62d431227b02528c76f5","hash":"99c952b90476f399c2b0a107e3068c5bd30c0cb557e4c7eeec858b2ea7e0cc5d"},{"seq":5,"id":"k6","ts":"2026-06-29T12:46:57.518Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c14","tier":"speculative","text":"Not established in this ledger: large randomized human trials for common marketed uses; long-term human safety beyond small pilots; condition-specific efficacy where only anecdotal or preclinical sources exist (explicit gaps remain in question graph).","who_claims":"miscsubjects gap analysis","source_ids":[],"slot":"what_is_unknown","posted_by":{"actor":"miscsubjects gap analysis","channel":"protocol/fill-slots","ts":"2026-06-29T12:46:57.518Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"99c952b90476f399c2b0a107e3068c5bd30c0cb557e4c7eeec858b2ea7e0cc5d","hash":"4b9de1282bddadc096beafc41aa0e07855b9a10c57c0cf49e1b8ef46b80771c7"},{"seq":6,"id":"k7","ts":"2026-06-29T12:46:57.577Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c15","tier":"mechanistic","text":"Hash-chained sources verify integrity, not clinical truth. Evidence mix is predominantly preclinical and anecdotal; human data are sparse. No dosing, protocol, or treatment recommendations — catalogue only.","who_claims":"miscsubjects protocol","source_ids":[],"slot":"limitations","posted_by":{"actor":"miscsubjects protocol","channel":"protocol/fill-slots","ts":"2026-06-29T12:46:57.577Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"4b9de1282bddadc096beafc41aa0e07855b9a10c57c0cf49e1b8ef46b80771c7","hash":"97ea47bbf6949344540b6eecd89ab2a80acbbed685be1ea3ab1b4f0ee747d9f2"},{"seq":7,"id":"k8","ts":"2026-06-29T12:46:57.610Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c16","tier":"human","text":"Not medical advice. Tier-honest research catalogue only — consult qualified healthcare professionals for personal health decisions.","who_claims":"miscsubjects protocol","source_ids":[],"slot":"disclaimer","posted_by":{"actor":"miscsubjects protocol","channel":"protocol/fill-slots","ts":"2026-06-29T12:46:57.610Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"97ea47bbf6949344540b6eecd89ab2a80acbbed685be1ea3ab1b4f0ee747d9f2","hash":"f2c3669673657dca17017b1239f9cb98616d26d5c9b63e9f8dd547a32c9ed83a"},{"seq":8,"id":"k9","ts":"2026-06-29T13:21:30.005Z","model":"kimi/moonshot-v1-8k","role":"collaborator","action":"collaborate","payload":{"claims_added":["c17","c18"],"challenge_id":"c19","rationale":"I am adding explicit gaps in knowledge regarding ARA-290 for carpal tunnel syndrome, as well as identifying who claims what from anecdotes that are not currently attributed to specific sources."},"rationale":"I am adding explicit gaps in knowledge regarding ARA-290 for carpal tunnel syndrome, as well as identifying who claims what from anecdotes that are not currently attributed to specific sources.","tokens_in":3163,"tokens_out":504,"cost":0.00055005,"prev_hash":"f2c3669673657dca17017b1239f9cb98616d26d5c9b63e9f8dd547a32c9ed83a","hash":"9bcc11b2380eaffd10a74d45ec2e819ee68ae6b953f8e5931a33cf5c285d5772"},{"seq":9,"id":"k10","ts":"2026-06-29T13:22:22.365Z","model":"kimi/moonshot-v1-8k","role":"collaborator","action":"collaborate","payload":{"claims_added":["c20","c21"],"challenge_id":"c22","rationale":"I am adding explicit gaps in knowledge (what_is_unknown) and identifying who claims what from anecdotes where this information is missing, as per the instructions."},"rationale":"I am adding explicit gaps in knowledge (what_is_unknown) and identifying who claims what from anecdotes where this information is missing, as per the instructions.","tokens_in":3314,"tokens_out":495,"cost":0.0005713499999999999,"prev_hash":"9bcc11b2380eaffd10a74d45ec2e819ee68ae6b953f8e5931a33cf5c285d5772","hash":"a1b1d6d38fff38130b98d5c9a350e8b796c6f6c307785be22387d41b7a9b1a05"},{"seq":10,"id":"k11","ts":"2026-06-29T14:49:58.531Z","model":"gemini/gemini-2.5-flash","role":"collaborator","action":"collaborate","payload":{"claims_added":["c23","c24"],"challenge_id":"c25","rationale":"Added claims to clarify the mechanistic basis of ARA-290 and highlight the unknown long-term efficacy and safety in humans. Challenged an incorrect tier classification for a human clinical trial claim to improve ledger accuracy, as I am Gemini, not Grok."},"rationale":"Added claims to clarify the mechanistic basis of ARA-290 and highlight the unknown long-term efficacy and safety in humans. Challenged an incorrect tier classification for a human clinical trial claim to improve ledger accuracy, as I am Gemini, not Grok.","tokens_in":3113,"tokens_out":454,"cost":0.000369675,"prev_hash":"a1b1d6d38fff38130b98d5c9a350e8b796c6f6c307785be22387d41b7a9b1a05","hash":"004022c0d1a54863cf9bd29cc8f873b740b045c8b7064becb407a9e963f769f1"},{"seq":11,"id":"k12","ts":"2026-06-29T14:50:50.386Z","model":"grok/grok-4.3","role":"editor","action":"synthesize_body","payload":{"chars":3443,"claims_used":21,"legibility":{"pass":true,"reasons":[]}},"rationale":"Reader body rewritten from ranked ledger topology — plain English","tokens_in":5615,"tokens_out":745,"cost":0.00888125,"prev_hash":"004022c0d1a54863cf9bd29cc8f873b740b045c8b7064becb407a9e963f769f1","hash":"af9e330cdb101a1c360ea0c003b391581a3078c4dca27b609c20ce8e5bcf2ba8"},{"seq":12,"id":"k13","ts":"2026-06-29T20:56:03.979Z","model":"fill-slots","role":"claim_post","action":"claim","payload":{"claim_id":"c25","tier":"system","text":"ARA-290 for Carpal Tunnel: Human Trial Data on Nerve Symptoms and Fiber Density is catalogued in this miscsubjects ledger as a tier-honest evidence graph (claims + hash-chained sources). This page summarizes what is claimed in the literature and online about the topic — not clinical recommendations.","who_claims":"miscsubjects protocol","source_ids":[],"slot":"what_it_is","posted_by":{"actor":"miscsubjects protocol","channel":"protocol/fill-slots","ts":"2026-06-29T20:56:03.979Z","model":"fill-slots","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"af9e330cdb101a1c360ea0c003b391581a3078c4dca27b609c20ce8e5bcf2ba8","hash":"df818df8ac310ea7153c0ebd06ee990d202c9fc8a25e0525bb9ea49cd1b6ba05"},{"seq":13,"id":"k14","ts":"2026-06-29T20:56:06.185Z","model":"fill-slots","role":"claim_post","action":"claim","payload":{"claim_id":"c26","tier":"mechanistic","text":"Hash-chained sources verify integrity, not clinical truth. Evidence mix is predominantly preclinical and anecdotal; human data are sparse. No dosing, protocol, or treatment recommendations — catalogue only.","who_claims":"miscsubjects protocol","source_ids":[],"slot":"limitations","posted_by":{"actor":"miscsubjects protocol","channel":"protocol/fill-slots","ts":"2026-06-29T20:56:06.185Z","model":"fill-slots","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"df818df8ac310ea7153c0ebd06ee990d202c9fc8a25e0525bb9ea49cd1b6ba05","hash":"2ad4a8f01e00a14f5e16c0634783e8b11a054b366a43b8902fa48d2bec0ee142"},{"seq":14,"id":"k15","ts":"2026-06-29T21:28:21.943Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s10","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/40216181/","title":"ARA290, an alternative of erythropoietin, inhibits activation of NLRP3 inflammasome in schwann cells after sciatic nerve injury","quote":"EPO and ARA290 promote repair and regeneration by inhibiting the activation of NLRP3 inflammasome after sciatic nerve injury.","link_status":"ok","quote_status":"verified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"2ad4a8f01e00a14f5e16c0634783e8b11a054b366a43b8902fa48d2bec0ee142","hash":"4217aa0c5436384adb1fdb9b3c80fd0a3d37566f7a8fd09319faafe8e22de9fe"}]}