ReviewJournal of pain research2016
The role of the arginine metabolome in pain: implications for sickle cell disease.
Review in Journal of pain research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Arginine Therapy for Pain in Sickle Cell Disease: A Phase-2 Randomized, Placebo-Controlled Trial.American journal of hematology · 2025Trial
- Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.American journal of respiratory and critical care medicine · 2022Trial
- Cerebrospinal Fluid Metabolites Mediate Immune Cell Effects on Chronic Pain.Molecular neurobiology · 2026Article
- Chrysin ameliorates pain through regulation of the serum metabolomics in the rats.The Korean journal of pain · 2025Article
- Enhanced anti-cancer efficacy of arginine deaminase expressed by tumor-seeking Salmonella Gallinarum.Oncogene · 2024Article
- Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition.International journal of molecular sciences · 2024Review
- Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?Expert review of hematology · 2024Review
- Sickle Cell Disease: Current Drug Treatments and Functional Foods with Therapeutic Potential.Current issues in molecular biology · 2024Review
- Arginine supplementation improves lactate dehydrogenase levels in steady-state sickle cell patients: preliminary findings from Kinshasa, the Democratic Republic of Congo.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- In vivo evaluation of the effect of sickle cell hemoglobin S, C and therapeutic transfusion on erythrocyte metabolism and cardiorenal dysfunction.American journal of hematology · 2023Article
- Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies.PloS one · 2023Article
- Metabolic correlates to critical speed in murine models of sickle cell disease.Frontiers in physiology · 2023Article
- L-Arginine supplementation enhanced expression of glucose transporter (GLUT 1) in sickle cell anaemia subjects in the steady state.Current research in physiology · 2023Article
- Increasing nitric oxide bioavailability fails to improve collateral vessel formation in humanized sickle cell mice.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Interactions among Endothelial Nitric Oxide Synthase, Cardiovascular System, and Nociception during Physiological and Pathophysiological States.Molecules (Basel, Switzerland) · 2022Review
- Metabolomic and proteomic characterization of sng and pain phenotypes in fibromyalgia.European journal of pain (London, England) · 2022Article
- Plasma Levels of Acyl-Carnitines and Carboxylic Acids Correlate With Cardiovascular and Kidney Function in Subjects With Sickle Cell Trait.Frontiers in physiology · 2022Article
- Characterization of plasma metabolites and proteins in patients with herpetic neuralgia and development of machine learning predictive models based on metabolomic profiling.Frontiers in molecular neuroscience · 2022Article
- Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways.Cells · 2020Article
- Sickle Cell Disease: Metabolomic Profiles of Vaso-Occlusive Crisis in Plasma and Erythrocytes.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sickle cell disease (SCD) is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO), polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its contribution to pain pathways likely extends beyond NO. Low global arginine bioavailability is associated with pain severity in both adults and children with SCD as well as other non-SCD pain syndromes. Preliminary clinical studies of arginine therapy in SCD demonstrate efficacy in treating acute vaso-occlusive pain, as well as leg ulcers and pulmonary hypertension. Restoration of arginine bioavailability through exogenous supplementation of arginine is, therefore, a promising therapeutic target. Phase II clinical trials of arginine therapy for sickle-related pain are underway and a Phase III randomized controlled trial is anticipated in the near future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.