DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for causalgia — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCausalgia maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for causalgia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
SMAD family member 3 (SMAD3) — SMAD3 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1MK2 · 2.74 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1943 monograph by W. K. Livingston proposed a physiologic interpretation of causalgia and related pain states, but provided no patient data or treatment outcomes. A 2003 meta-analysis of 110 articles covering 1528 cases found that high-velocity missiles caused at least 77% of injuries. Onset of pain occurred within one week in 72% of cases and within one month in 90%. The median nerve alone or with other nerves was involved in 56% of cases, and sciatic trunk injury in 60%. The nerve injury was incomplete in 92%. Burning pain was reported in 86%, increased sweating in 73%, paresthesias in 96%, and sensitivity to stimuli in 98%. Response to sympathetic blocks was observed in 88%. Among patients who underwent sympathectomy, 94% were reported cured. The authors concluded that causalgia is easy to recognise and treat with excellent results.
A 1984 report described eleven patients whose causalgia resulted from surgical procedures or improperly placed injections. The authors argued against dividing causalgia into major and minor forms based on wartime versus peacetime occurrence or presence of autonomic dysfunction. All cases with completed legal proceedings were settled in favour of the plaintiffs. A 1985 study of 14 patients treated with intrafascicular decompression reported that all except one were cured, with no symptomatic recurrence over four to six years of follow-up. The authors proposed endoneural hypertension secondary to nerve trunk disruption as the mechanism.
A 1996 review proposed that peripheral electrical nerve stimulation might counteract central nervous system alterations in causalgia by decreasing release of pain-mediating neurotransmitters in the spinal cord and reducing sensitisation of dorsal horn neurons. No patient data or outcomes were presented. No randomised controlled trials, no placebo-controlled comparisons, and no standardised diagnostic criteria have been established for this condition. The evidence base consists entirely of case series and meta-analyses of case series, with no prospective trials, no blinding, and no systematic assessment of spontaneous recovery or placebo effects.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Physical Therapy · 1944 · 164 citations
Pain Mechanisms: A Physiologic Interpretation of Causalgia and its Related States
AbstractJournal Article Pain Mechanisms: A Physiologic Interpretation of Causalgia and its Related States Get access Pain Mechanisms: A Physiologic Interpretation of Causalgia and its Related States. By W. K. Livingston, M. D., Lieutenant Commander, United States Naval Reserve. Cloth. Price, $3.75. Pp. 253, with 26 illustrations. New York: The Macmillan Company, 1943. Physical Therapy, Volume 24, Issue 1, January-February 1944, Page 46, https://doi.org/10.1093/ptj/24.1.46 Published: 01 January 1944
AbstractBACKGROUND: Causalgia is not familiar to most physicians whose training and experience are limited to civilian practice. HYPOTHESIS: Through a thorough review of the literature, we attempted to determine the boundaries of causalgia and separate it from other sympathetically related disorders. DATA SOURCES: Database search for English-language articles in MEDLINE and Index Medicus up to the year 2000 as both keyword and subject under causalgia. STUDY SELECTION: References that described any new cases referred to as "causalgia" by their authors were included in a meta-analysis. DATA SYNTHESIS: One hundred ten articles contained a total of 1528 cases of causalgia. High-velocity missiles caused at least 77% of the injuries. In 72% and 90% of the cases reported, the time from injury to onset of pain was within 1 week and 1 month, respectively. Median nerve alone or in combination with other nerves (56%) and sciatic trunk injury (60%) were the most common nerves involved. In 92%, the nerve injury was incomplete. The most prominent clinical manifestations included burning pain in 86%, increased sweating in 73%, relief with application of cold in 62%, warmth in 50%, paresthesias in 96%, absence of anesthesia in 81%, and sensitivity to stimuli in 98%. Response to sympathetic blocks was observed in 88%. Finally, a total of 94% of the patients undergoing sympathectomy were cured. CONCLUSIONS: Cases of causalgia are easy to recognize and treat, with excellent results. Causalgia always follows a somatic nerve injury, usually partial, and is associated with near-constant, very severe pain distal to the injury in the extremity, varied in nature but characteristically with a predominantly burning quality. An effective anesthetic block of the appropriate part of the sympathetic chain frequently immediately relieves the pain. Most cases are cured by surgical sympathectomy.
AbstractEleven patients had causalgia that resulted from surgical procedures or improperly placed injections. It is the intense, unremitting, burning quality of the pain that distinguishes causalgia from other nerve injury sequelae. The mode of injury, as well as the symptoms and signs and their duration, suggests that the recent tendency to divide causalgia into "major" and "minor" forms on the basis of its occurrence during war or peace, with or without autonomic dysfunction, is improper. Most of these patients have sought legal redress. All cases for which the legal issues are complete have been settled in favor of the plaintiffs.
Intrafascicular Decompression in the Treatment of Gausalgia with Special Reference to the Mechanism
AbstractA new concept of the pathogenesis of causalgia is suggested in accordance with experimental and clinical work. Endoneural hypertension secondary to nerve trunk disruption is incriminated and intrafascicular decompression is used as the key therapeutic measure. In 14 patients with causalgia thus treated, all except 1 were cured. No symptomatic recurrence was noted in a 4- to 6-year follow-up study.
The neurophysiological basis of peripheral electrical nerve stimulation for the treatment of causalgia
AbstractCausalgia is a syndrome where constant and burning pain can develop in the extremities following damage to a peripheral nerve. It is likely that the symptoms of this syndrome are produced by alterations in the normal function of the peripheral and central nervous systems. In the central nervous system, there is an increased release of neurotransmitters from the axons of damaged peripheral nerves terminating in the spinal cord. Also in the spinal cord, there is a long-lasting sensitization of dorsal hom neurons to sensory stimulation. Two mechanisms by which peripheral electrical nerve stimulation is believed to produce analgesia are through decreasing the release of pain-mediating neurotransmitters in the spinal cord and by reducing the sensitivity of dorsal hom neurons to sensory stimulation. Because peripheral electrical nerve stimulation directly opposes the central nervous system alterations that occur with causalgia, it seems an ideal treatment for this debilitating syndrome.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
