{"slug":"ara-290-gabapentin-lyrica","verification":{"valid":true,"entries":13,"head":"435ff590474a72a919e841e75aa4bfe30204a1d9c2792743c048b950628174ba"},"count":13,"models":["grok/grok-4.3","grok-4.3","system/audit-repair","kimi/moonshot-v1-8k","gemini/gemini-2.5-flash"],"yield":{"passes":13,"energy_spent_rows":0,"total_cost_usd":0.01299,"waste_cost_usd":0,"total_tokens":18846,"material_outputs":7,"usd_per_output":0.001856,"models":[{"model":"kimi/moonshot-v1-8k","passes":2,"cost_usd":0.001075,"tokens_total":7164,"outputs":4,"waste_passes":0,"usd_per_output":0.000269},{"model":"gemini/gemini-2.5-flash","passes":1,"cost_usd":0.000349,"tokens_total":3348,"outputs":3,"waste_passes":0,"usd_per_output":0.000116},{"model":"grok-4.3","passes":5,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"system/audit-repair","passes":3,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"grok/grok-4.3","passes":2,"cost_usd":0.011566,"tokens_total":8334,"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":"2026-06-29T08:53:08.999Z","model":"grok/grok-4.3","role":"writer","action":"redraft","payload":{"title":"ARA-290 vs Gabapentin and Lyrica: Human Trial Data on Nerve Repair Versus Signal Suppression","register":"source_ledger","body":"## Overview of Mechanisms\n\nGabapentin and pregabalin (Lyrica) bind to the α2δ subunit of voltage-gated calcium channels, reducing neurotransmitter release and dampening nerve signal transmission (human mechanistic data from reviews). No human data demonstrate reversal of underlying nerve damage.\n\nARA-290 is an 11-amino-acid peptide derived from erythropoietin that selectively activates the innate repair receptor (IRR). Human clinical trials report increased corneal nerve fiber density and symptom improvement in small fiber neuropathy.\n\n## Human Clinical Data on ARA-290\n\nIn a randomized double-blind placebo-controlled trial of 49 adults with type 2 diabetes and painful neuropathy, daily subcutaneous ARA-290 4 mg for 28 days improved neuropathic symptoms on PainDetect questionnaire versus placebo (human trial data). Corneal nerve fiber regeneration was observed in sarcoidosis-associated small fiber neuropathy trials (human data).\n\nNo human data exist on direct head-to-head comparison of ARA-290 versus gabapentin or pregabalin.\n\n## Side Effect Profiles\n\nGabapentin and pregabalin are associated with dizziness, somnolence, weight gain, and cognitive effects in human clinical use (review data). ARA-290 trials reported no relevant adverse events in the studied populations (human trial data).\n\n## Repair Versus Suppression Framing\n\nGabapentinoids reduce pain signaling without evidence of nerve regrowth in human studies. ARA-290 human trials link symptom changes to measurable increases in nerve fiber density, consistent with repair pathway activation rather than signal masking.\n\n## Evidence Limitations\n\nAll direct efficacy comparisons between ARA-290 and gabapentinoids remain speculative due to absence of comparative human trials. Preclinical data exist for ARA-290 nerve repair but are separated from human findings here.","claims":[{"id":"c1","text":"Gabapentin and pregabalin bind to the α2δ subunit of voltage-gated calcium channels, reducing neurotransmitter release and dampening nerve signal transmission.","section":"Overview of Mechanisms","tier":"human","source_ids":["s1"],"source_status":"sourced","why_material":"Establishes suppression mechanism baseline","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c2","text":"ARA-290 selectively activates the innate repair receptor (IRR) leading to reported increases in corneal nerve fiber density in human sarcoidosis neuropathy trials.","section":"Human Clinical Data on ARA-290","tier":"human","source_ids":["s2","s3"],"source_status":"sourced","why_material":"Core evidence of repair versus masking","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c3","text":"In a Phase 2 human trial of 49 adults with type 2 diabetes, 28 days of ARA-290 4 mg daily improved PainDetect neuropathic symptom scores versus placebo.","section":"Human Clinical Data on ARA-290","tier":"human","source_ids":["s3"],"source_status":"sourced","why_material":"Quantified symptom change in controlled setting","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c4","text":"No human data exist on direct head-to-head efficacy or safety comparison of ARA-290 versus gabapentin or pregabalin.","section":"Evidence Limitations","tier":"speculative","source_ids":[],"source_status":"unsourced","why_material":"States absence of comparative evidence plainly","evidence_basis":"derived_inference","weight":0.1,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c5","text":"Gabapentin and pregabalin are associated with dizziness, somnolence, weight gain, and cognitive effects in human clinical use.","section":"Side Effect Profiles","tier":"human","source_ids":["s4"],"source_status":"sourced","why_material":"Documents known suppression-related side effects","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}}],"sources":[{"id":"s1","type":"review","url":"https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2024.1513597/full","title":"Pregabalin vs. gabapentin in the treatment of neuropathic pain","quote":"Both drugs bind to the α2δ subunit of calcium channels in neurons, but pregabalin exhibits greater affinity and potency in its binding","link_status":"ok","quote_status":"verified"},{"id":"s2","type":"pubmed","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5741312/","title":"Targeting the innate repair receptor to treat neuropathy","quote":"In patients with sarcoidosis, ARA290 significantly improved neuropathic and autonomic symptoms... ARA290 treatment for 28 days initiated a regrowth of small nerve fibers in the cornea","link_status":"ok","quote_status":"unverified"},{"id":"s3","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":"Subjects receiving ARA 290 exhibited an improvement in hemoglobin A(1c) (Hb A(1c)) and lipid profiles... Neuropathic symptoms as assessed by the PainDetect questionnaire improved significantly in the ARA 290 group","link_status":"ok","quote_status":"unverified"},{"id":"s4","type":"review","url":"https://www.pharmacytimes.com/view/how-gabapentin-differs-from-pregabalin","title":"Gabapentin Differs From Pregabalin in Several Key Ways","quote":"Dizziness and somnolence are the most common side effects in both drugs (>20% seen in gabapentin). Confusion and peripheral edema have also been reported","link_status":"ok","quote_status":"unverified"}]},"rationale":"","tokens_in":0,"tokens_out":0,"prev_hash":"genesis","hash":"d80659816fe0b633e39a0b216a9161b50a0b7a49a99c6e04a471dd4fded97845"},{"seq":1,"id":"k2","ts":"2026-06-29T10:34:22.359Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s5","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/v44s3q/effectiveness_of_ara290my_assessment/","title":"Effectiveness of ARA-290...My Assessment","quote":"So far, so good and my dosage for gabapentin, has gone down from 2400 mg/day to 800-1600 mg/day ... I am now completely off gabapentin ... I now no longer take gabapentin and my ARA290 is 4mg daily for a month and then I take a break.","link_status":"ok","quote_status":"unverified"},{"id":"s6","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1o33123/peptide_ara290/","title":"Peptide ARA-290","quote":"Has anyone tried the peptide ARA-290 . It has clinical evidence of helping to slow or stop neuropathy and allow nerves to heal.","link_status":"ok","quote_status":"unverified"},{"id":"s7","type":"clinical_trial","url":"https://clinicaltrials.gov/study/NCT02039687","title":"Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms in Patients With Sarcoidosis","quote":"The purpose of this study is to determine whether ARA 290 , a new class of compound, is effective in the treatment of the neuropathic symptoms of sarcoidosis ...","link_status":"ok","quote_status":"unverified"},{"id":"s8","type":"medical","url":"https://mindbodyneurology.com/ara-290-peptide-neuropathy/","title":"ARA 290 Peptide for Neuropathy and Neurodegeneration","quote":"Standard options such as duloxetine, gabapentin, pregabalin, and tricyclics still play a role for many patients. ARA 290 research points toward an adjunct that targets root mechanisms.","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"prev_hash":"d80659816fe0b633e39a0b216a9161b50a0b7a49a99c6e04a471dd4fded97845","hash":"f18c893a9258ffffba36e720b620128f3e7f7c9f811ee85aed4646c4f8b1b695"},{"seq":2,"id":"k3","ts":"2026-06-29T10:34:43.951Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s9","type":"clinical_trial","url":"https://clinicaltrials.gov/study/NCT06626971","title":"The Use of ARA290 for the Treatment of Diabetic Macular Edema","quote":"ARA 290 is a drug that has marked anti-inflammatory properties and has an effect in preventing the death of cells. As inflammation is known to play a role in ...","link_status":"ok","quote_status":"unverified"},{"id":"s10","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/40216181/","title":"ARA290, an alternative of erythropoietin, inhibits activation ...","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"},{"id":"s11","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":"These experimental and clinical studies show that ARA290 effectively reprograms a proinflammatory, tissue-damaging milieu into one of healing and tissue repair.","link_status":"ok","quote_status":"verified"},{"id":"s12","type":"medical","url":"https://bamapain.com/sciatica/","title":"Leg Pain & Sciatica Treatment Birmingham AL","quote":"Gabapentin reduces neuropathic leg pain by fifty percent in roughly one out of six patients . ARA-290 has the most advanced clinical evidence of any peptide for ...","link_status":"ok","quote_status":"unverified"},{"id":"s13","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/vlbxty/ara290_for_neuropathic_pain/","title":"ARA-290 for Neuropathic Pain","quote":"~ 50% improvement in my condition (length-dependent ・ a hint of peripheral nerve healing/regeneration.","link_status":"ok","quote_status":"unverified"},{"id":"s14","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1tncdyo/ara290_peptide_and_rebuilder_2407_have_changed_my/","title":"ARA290 peptide AND Rebuilder 2407 have changed my life!","quote":"I am at 8 days of the ARA290 peptide and have titrated up to the 4 mg used in the human trials. ... Yesterday was by FAR the best day of the past 15 months!","link_status":"ok","quote_status":"unverified"},{"id":"s15","type":"youtube","url":"https://www.youtube.com/watch?v=xggIEy1ZfM8","title":"Small Fiber Neuropathy and ARA-290 Results","quote":"ARA 290 is a potential therapy currently being researched for its safety and efficacy for the treatment of neuropathic pain in patients with sarcoidosis","link_status":"http_429","quote_status":"unverified"},{"id":"s16","type":"other","url":"https://peptidefox.com/content/ara-290","title":"ARA-290: Tissue-Protective Peptide for Nerve Pain","quote":"The strongest human data is narrow but real. In Phase 2 trials in sarcoidosis-associated small fiber neuropathy, and one trial in painful diabetic neuropathy, ARA-290 increased objective markers of small-nerve regeneration","link_status":"ok","quote_status":"verified"}]},"rationale":"auto-populate round 2","tokens_in":0,"tokens_out":0,"prev_hash":"f18c893a9258ffffba36e720b620128f3e7f7c9f811ee85aed4646c4f8b1b695","hash":"e38d45214f816d0e59c1b63e4a1ae137220e132258fb1b819d0805a6021b5a9f"},{"seq":3,"id":"k4","ts":"2026-06-29T10:35:01.874Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s17","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/hreepv/ara290_peptide_any_experience_reports/","title":"ARA-290 peptide — any experience reports? : r/neuropathy","quote":"I am almost done with a month of ara 290 . I'm not part of a trial but I am using it. It's not cheap. I have seen really great results. My ... I've tried everything you can imagine, from red light therapy, acupuncture, deep tissue massages, pregabalin, gabapentin etc. Unfortunately, when there is nerve damage there is very little one can do and I don't want to be on meds the rest of my life, not to mention they don't really work, at least for me.","link_status":"ok","quote_status":"unverified"},{"id":"s18","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":"I've started ARA-290 and I’m planning to run a 28-day cycle to see if it helps with my neuropathic pain. ... I tried pregabalin but it was horrible. ... UPDATE (07.06.2026) I had to take 2 days off from it as I was abroad and not able to take it with me. I was on it for less than a week and didn't notice any benefits nor side effects.","link_status":"ok","quote_status":"unverified"},{"id":"s19","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1kakzrn/reconstitute_ara290_in_nacl_09_instead_of_pbs/","title":"Reconstitute ARA-290 in NaCL 0.9% instead of PBS? : r/smallfiberneuropathy","quote":"I haven't seen any improvement after trying it for several months, hope it works for you","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 3","tokens_in":0,"tokens_out":0,"prev_hash":"e38d45214f816d0e59c1b63e4a1ae137220e132258fb1b819d0805a6021b5a9f","hash":"03b0931b4f8fbb4550fd8e8d4b478bc9df3626816bd95cf85169839809a6bc63"},{"seq":4,"id":"k5","ts":"2026-06-29T10:35:30.366Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s20","type":"instagram","url":"https://www.instagram.com/reel/DVjz4bDDZJn/","title":"Instagram reel on ARA 290 for neuropathy vs Gabapentin/Lyrica","quote":"If you have neuropathy or chronic nerve pain, standard medicine tells you to “live with it” while prescribing Gabapentin or Lyrica. ... Enter ARA 290 (Cibinetide).","link_status":"ok","quote_status":"unverified"},{"id":"s21","type":"review","url":"https://www.nature.com/articles/s41392-025-02175-1","title":"Diabetic neuropathy: cutting-edge research and future ...","quote":"A double-blind, placebo-controlled, investigator-initiated clinical trial showed that ARA 290 benefited both metabolic control and neuropathic ... Current management strategies primarily focus on alleviating symptoms and controlling pain. [11] Antidepressants, anticonvulsants, and opioids have shown limited efficacy...","link_status":"ok","quote_status":"unverified"},{"id":"s22","type":"other","url":"https://bcb.bme.gatech.edu/cgi-bin/crispr/news.cgi?p=2026-s-ara-290-peptide-craze-the-biohacking-movement-chronic-pain-patients-can-t-quit-6a1b07505f5d2","title":"The Biohacking Movement Chronic Pain Patients Can't Quit","quote":"The promise is seductive: a molecule that can repair nerves and extinguish inflammation without the classic side effects of gabapentin or the risks of opioids.","link_status":"ok","quote_status":"unverified"},{"id":"s23","type":"medical","url":"https://www.seekpeptides.com/blog/articles/peptides-for-neuropathy","title":"the complete guide to nerve repair and pain relief","quote":"What sets ARA-290 apart mechanistically is that it does not simply mask pain . It reduces the underlying inflammation driving nerve damage and ... It is one of the few compounds with human evidence of nerve-fiber regeneration markers, rather than only symptom suppression like gabapentin or duloxetine.","link_status":"ok","quote_status":"unverified"},{"id":"s24","type":"medical","url":"https://www.bettermedspa.com/treatments/rewire-ara-290","title":"ReWire (ARA-290) Peptide Therapy Lincoln Park","quote":"For patients in Chicago dealing with neuropathic symptoms that have resisted gabapentin, pregabalin, or duloxetine, this mechanism offers a fundamentally different approach: rather than dulling pain signals, ReWire addresses the structural and inflammatory roots of nerve dysfunction.","link_status":"ok","quote_status":"verified"}]},"rationale":"auto-populate round 4","tokens_in":0,"tokens_out":0,"prev_hash":"03b0931b4f8fbb4550fd8e8d4b478bc9df3626816bd95cf85169839809a6bc63","hash":"2c5f3ecb6f363539d57edda38e75baeda148132fe150370b98020015cab0aee3"},{"seq":5,"id":"k6","ts":"2026-06-29T12:48:10.510Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c26","tier":"preclinical","text":"Per this ledger on ARA-290 vs Gabapentin and Lyrica: Human Trial Data on Nerve Repair Versus Signal Suppression: 13 scientific and 9 anecdotal sources are catalogued; 5 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":"2026-06-29T12:48:10.510Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"2c5f3ecb6f363539d57edda38e75baeda148132fe150370b98020015cab0aee3","hash":"7a555862706d24b5f23340a1f181456a9d99645ff36b80cd9aa8f7ecf64b1fc3"},{"seq":6,"id":"k7","ts":"2026-06-29T12:48:10.551Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c27","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":"2026-06-29T12:48:10.551Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"7a555862706d24b5f23340a1f181456a9d99645ff36b80cd9aa8f7ecf64b1fc3","hash":"f8e411b25085d02bec0a9dcc89534a5ece0ed135680c655a45868898cb7100e7"},{"seq":7,"id":"k8","ts":"2026-06-29T12:48:10.598Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c28","tier":"human","text":"Not medical advice. 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Gabapentin helps him but the pain seems to still be worse at times, more so than say a year ago.","link_status":"ok","quote_status":"unverified"},{"id":"s26","type":"reddit","url":"https://www.reddit.com/r/Biohack_Blueprint/comments/1qf1t16/nerve_damage_wont_heal_ara290_complete_guide/","title":"Nerve Damage Won't Heal → ARA-290 Complete Guide","quote":"Most neuropathy treatments work downstream. Gabapentin and pregabalin modulate calcium channels to reduce pain signaling.","link_status":"ok","quote_status":"unverified"},{"id":"s27","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/1fei315/any_success_at_easing_nerve_damage_from_longcovid/","title":"Any success at easing nerve damage from longcovid?","quote":"I have to go on Gabapentin and Duloxetine to stop the severe burning pain. ... I would look into ARA 290.","link_status":"ok","quote_status":"unverified"},{"id":"s28","type":"x","url":"https://x.com/PeptidesFinder/status/2047760738371125595","title":"","quote":"Nerve pain is usually treated with drugs that just numb your brain (Gabapentin). They mask the signal. They don't fix the wire. You need something that targets the \"Innate Repair Receptor.\" Meet ARA-290 (The Nerve Healer). It stops the pain and regrows the fiber.","link_status":"ok","quote_status":"unverified"},{"id":"s29","type":"x","url":"https://x.com/PeptidesFinder/status/2039040304800571738","title":"","quote":"Chronic pain (Neuropathy) is usually treated with gabapentin or opioids. These drugs act like \"volume knobs\"—they turn down the signal, but the wire stays broken. Science has found a peptide designed to physically repair the wire. Meet ARA-290 (Cibinetide).","link_status":"ok","quote_status":"unverified"},{"id":"s30","type":"x","url":"https://x.com/Zedzies/status/2019107972837003451","title":"","quote":"And those small nerves just don’t innervate skin. They innervate other organs as well. ARA-290 Erinacine (Lions mane) Psilocybin All can regrow/repair. Gabapentin only masks.","link_status":"ok","quote_status":"verified"},{"id":"s31","type":"x","url":"https://x.com/BOENGLISH1/status/1912566621115486518","title":"","quote":"There are quite a few therapies which could help people get off gabapentin and similar drugs: ara-290, NA R-ALA, hyperbaric O2, and red light therapy","link_status":"ok","quote_status":"verified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"b09e90ffc2e94e1ad9e7e00a87e39c95bbcf6a5666bd96f706c7a95d19ba83f5","hash":"435ff590474a72a919e841e75aa4bfe30204a1d9c2792743c048b950628174ba"}]}