DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for complex regional pain syndrome — screening already-approved drugs against its 34-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleComplex regional pain syndrome maps to a 34-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
approvedKetamineApproved drugapprovedMemantineApproved drug
Structures already discussed alongside complex regional pain syndrome in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
X-ray Structure of the Anesthetic Ketamine — Ketamine has a real, experimentally solved structure in complex with this target (PDB 4F8H, 2.99 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
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helix sheet rkedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4F8H · 2.99 Å · ligand Ketamine (RKE). Experimental structure, not a prediction.
What the evidence adds up to
No randomised controlled trial has shown a drug to be effective for complex regional pain syndrome. A 2005 review states that there is very little evidence supporting any effective treatment, and that what is used in clinical practice is extrapolated from trials in other neuropathic pain conditions. A 2016 review agrees, saying drugs used for neuropathic pain have been suggested but none possess sufficient evidence. It adds that there is low evidence that bisphosphonates, calcitonin, ketamine and mirror therapy are effective compared to placebo. A 2008 review estimates that 20% to 35% of patients will remain incapacitated indefinitely and only 20% to 30% will return to their previous full-time employment.
The condition has been recognised for over 100 years, yet no clear evidence exists for first-line treatments. A 2013 review of patients with long-standing complex regional pain syndrome notes that approximately 15% of patients will show no improvement within the first 12 months and should be considered as having a long-term condition. It states that conclusive evidence is still lacking for almost all aspects of care, and that meaningful pain relief is often not achieved with currently available treatment methods. Multidisciplinary functional rehabilitation is recommended, but this does not reliably provide pain relief.
Early stage use of NSAIDs or steroids is mentioned in the 2016 review, but without trial data supporting efficacy. Interventional treatments such as epidural block, neurostimulation and intrathecal pumps are described as stepped options for intractable pain, but again without evidence from controlled trials. The 2013 review says that novel treatment approaches will probably provide more patients with long-term pain relief in the future, but that confirmatory trials are required.
What is still missing is any adequately powered, placebo-controlled trial that demonstrates a drug or intervention changes the natural history of the disease. Patient stratification is absent: no mechanism-based diagnostic scheme exists to identify who might respond to what. The funding and trial design needed to generate that evidence have not been forthcoming.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Physical Medicine & Rehabilitation · 2005 · 58 citations
Pharmacotherapy of Complex Regional Pain Syndrome
AbstractComplex regional pain syndrome has both nociceptive/inflammatory and neuropathic elements and is always (by definition) associated with abnormal activity of the sympathetic nervous system. There is good evidence that complex regional pain syndrome, as currently conceptualized, ultimately includes central sensitization and has motor abnormalities. The lack of a standard diagnostic test or a specific mechanistically based diagnostic scheme has hindered the conduct of well-designed trials, and to date, there is very little evidence supporting an effective treatment. Fortunately, some randomized, controlled trials of drug therapies have been conducted, and systematic reviews have been published of related neuropathic conditions, from which the results have been extrapolated to clinical use in complex regional pain syndrome. The following article presents an overview of available data regarding drug and interventional treatment options for complex regional pain syndrome and of those relevant pharmacotherapies we can derive from the neuropathy literature. As with most chronic pain syndromes, pharmacotherapy coupled with functional restoration and an interdisciplinary approach to treatment are essential to a successful outcome.
Cirugía y Cirujanos · 2016 · 17 citations · open access
Síndrome doloroso regional complejo: revisión
AbstractEl síndrome doloroso regional complejo se caracteriza por dolor espontáneo o inducido, desproporcionado con relación al evento inicial y que se acompaña de una gran variedad de alteraciones autonómicas y motoras, dando lugar a una gran variedad de presentaciones clínicas. Con frecuencia se asocia a cirugías y a traumatismos menores. Se postulan 3 mecanismos: cambios por inflamación postraumática, disfunción vasomotora periférica y cambios funcionales y estructurales del sistema nervioso central secundarios a una mala adaptación. Se realiza tomando como base los criterios de Budapest. El paciente debe presentar un síntoma de cada criterio al momento del diagnóstico: dolor continuo, desproporcionado en relación con cualquier evento desencadenante. Un signo y un síntoma: sensorial, vasomotor, edema y cambio motor / trófico. Por último, estos no se explican por otro diagnóstico o causa. Se sugiere que sea multimodal. No existe un estándar de oro. En fase temprana se pueden utilizar AINE o esteroides. Se han indicado fármacos utilizados para tratamiento de dolor neuropático, pero ninguno de estos posee suficiente evidencia. Hay baja evidencia de la efectividad de que los bifosfonatos, la calcitonina, la ketamina y la terapia en espejo sean efectivos comparados con placebo. El tratamiento intervencionista debe ser escalonado de bloqueo peridural, neuroestimulación, bomba intratecal hasta las terapias experimentales en caso de dolor refractario a tratamiento. A pesar de que el síndrome doloroso regional complejo es una entidad reconocida desde hace más de 100 años, todavía no existe evidencia clara en las primeras elecciones terapéuticas, aunque hay nuevas tecnologías aplicables en su tratamiento. Complex regional pain syndrome is characterized by spontaneous or induced pain disproportionate in relation to the initial event and is accompanied by a variety of regional and motor disturbances, leading to a variety of clinical presentations. It is often associated with surgery and minor trauma. Three mechanisms are postulated: changes secondary to post traumatic inflammation, peripheral vasomotor dysfunction and structural and functional changes of the central nervous system as a result of maladaptation. made based on the criteria of Budapest. The patient must have one symptom and sign of each criterion at diagnosis: Continuing pain, disproportionate to any inciting event. A sensory, vasomotor, oedema and motor/trophic change sign and symptoms that are not explained by another diagnosis or cause. Multimodal treatment is suggested. There is no gold standard. In early stage NSAIDs or steroids can be used. Drugs used for neuropathic pain treatment have been suggested, but there is not enough evidence for any of these. There is low evidence that bisphosphonates, calcitonin, ketamine and mirror therapy are effective compared to placebo. Interventional treatment should be stepped from epidural block, neurostimulation, intrathecal pump to experimental therapies in case of intractable pain. Although complex regional pain syndrome has been a recognized entity for over 100 years, no clear evidence exists for first-line treatments; however, new technologies that are applicable in complex regional pain syndrome treatment have been developed.
Management of Adult Patients with Long-Standing Complex Regional Pain Syndrome
AbstractSUMMARY Approximately 15% of patients with complex regional pain syndrome will experience no improvement in their condition within the first 12 months. This group should be considered as having a long-term condition. Recently published clinical studies and national guidelines can support clinicians to devise rational approaches to the management of this group; however, conclusive evidence is still lacking for almost all aspects of care. A multidisciplinary approach to managing long-standing complex regional pain syndrome appears best suited to ensure high-quality care. This should allow effective functional rehabilitation. Unfortunately, however, meaningful pain relief is often not achieved with currently available treatment methods. Recently published novel treatment approaches will probably provide more patients with long-term pain relief in the future, but confirmatory trials are required.
Morphine and Memantine Treatment of Long-Standing Complex Regional Pain Syndrome: Table 1
AbstractDear Editor: Long-standing complex regional pain syndrome (CRPS) is difficult to treat and an effective oral regimen would be welcome. A recent randomized controlled trial in long-standing upper limb CRPS reported by Gustin et al. demonstrated significant pain relief, with minimal side effects in 10 patients, with an oral combination treatment of morphine and memantine [1]. Pain at rest/on movement was reduced by half or greater in 60%/70% of patients. Fifty percent of participants were male, and 60% had CRPS II. These characteristics are not typical for patients seen at our center. I therefore wished to confirm whether the described treatment would benefit my patients; I conducted a prospective registered audit.1 Ten consecutive patients with long-standing CRPS diagnosed according to Budapest criteria [2] were treated, who attended over a period of 4 weeks in October/November 2010 and who had not responded to other medical treatments. The patients completed a Brief Pain Inventory [3] both before and 6 weeks into the audit. Variations between this audit and the published (intervention arm) data related to the patients' sex (10% vs 50% male), mean age (40 vs 51 years), the audit patients' higher disease duration (32 vs 15.6 months), CRPS type (type II in 10%/60%), the affected limb (upper in 20%/100%), the higher baseline pain (8.1−24 hours average pain numerical rating scale taken before the first treatment day—vs 67—visual analog scale average of rest and movement pain over 5 days before treatment), the endpoint (6/8 weeks after morphine start—in the study the results of the 6 and 8 weeks were congruent), and participant adherence (33% vs 0% were unable to continue on full dose). At 6 weeks, none of my patients had experienced pain reduction by half or more, and some recorded bothersome side effects (Table 1). Demographics, disease characteristics, and treatment outcome in 10 patients with CRPS treated over 6 weeks with 10 mg Morphine TDS and 20 mg BD Memantine using a recently published uptitration protocol [1] This patient reduced her dose to 10 mg BD from end of week 2. This patient reduced her dose to 15 mg BD from end of week 2. This patient dropped her dose to 5 mg BD after 3 days on full dose. CRPS NOS: This patient had several specialist-documented limb signs in the past, but did only have one sign on examination. M = male/F = female; U/l = upper/lower limb; Pain pre/post = 24 h average pain intensity before/6 weeks into treatment; Med = median; NA = not applicable. BPI = Brief Pain Inventory interference subscale (the ability to walk was not calculated in patients with upper limb CRPS) [3]. One patient (#10) felt that the BPI pain value did not reflect his dramatic improvement. He subsequently wrote two letters indicating that he obtained excellent and meaningful, ongoing pain relief. Three patients (#1, #3, #10) decided to continue their treatment after the audit had ended. Demographics, disease characteristics, and treatment outcome in 10 patients with CRPS treated over 6 weeks with 10 mg Morphine TDS and 20 mg BD Memantine using a recently published uptitration protocol [1] This patient reduced her dose to 10 mg BD from end of week 2. This patient reduced her dose to 15 mg BD from end of week 2. This patient dropped her dose to 5 mg BD after 3 days on full dose. CRPS NOS: This patient had several specialist-documented limb signs in the past, but did only have one sign on examination. M = male/F = female; U/l = upper/lower limb; Pain pre/post = 24 h average pain intensity before/6 weeks into treatment; Med = median; NA = not applicable. BPI = Brief Pain Inventory interference subscale (the ability to walk was not calculated in patients with upper limb CRPS) [3]. One patient (#10) felt that the BPI pain value did not reflect his dramatic improvement. He subsequently wrote two letters indicating that he obtained excellent and meaningful, ongoing pain relief. Three patients (#1, #3, #10) decided to continue their treatment after the audit had ended. Patient characteristics and/or selection criteria may be responsible for the dramatic differences in efficacy observed between the two studies, but larger trials are required to investigate predictive factors for a beneficial response. These data suggest that patients considered for this treatment should be told that the probability for success is currently uncertain, and that severe cognitive adverse reactions may occur not infrequently. Prof. A. Vincent and Prof. T. Nurmikko are thanked for their important suggestions. The author declares no conflict of interest regarding this article
Pharmacotherapy for Treatment of Complex Regional Pain Syndrome
AbstractComplex regional pain syndrome (CRPS) is an ill-defined, poorly understood disorder that causes significant morbidity in those who suffer from it. It is estimated that up to 20% to 35% of patients will remain incapacitated indefinitely and that only 20% to 30% of patients will be able to return to their previous full-time employment. A number of treatments, interventional and noninterventional, have been posited as possible therapies for CRPS. We discuss and review here the evidence-based rationale for pharmacologic therapy for CRPS.
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.
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