ArticleBritish journal of haematology2016
Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use.
Article in British journal of haematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 25 papers.
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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.
Safety and Feasibility of High-Dose Topical Capsaicin for the Treatment of Neuropathic Pain in Pediatric Sickle Cell Disease
Comparison of Efficacy Between Bilateral Superficial Cervical Plexus Block and Local Infiltration of Lidocaine 2% in Patients Undergoing Tracheostomy
Who cites it
25 citing papers in PubMed.
- Increasing daily step counts improves physical fitness, and reduces pain and arterial stiffness in sickle cell patients.Haematologica · 2026Trial
- Emerging preclinical evidence supports a potential role for cannabidiol in the management of sickle cell disease.Haematologica · 2026Review
- A novel palmitoylethanolamide formulation improves hyperalgesia and red cell instability in murine sickle cell disease.Blood vessels, thrombosis & hemostasis · 2026Article
- Neuroprotective, anti-inflammatory, and analgesic activity of palmitoylethanolamide in sickle cell mice.Blood advances · 2025Article
- The Role of Biomarkers in Acute Pain: A Narrative Review.Pain and therapy · 2025Review
- Article
- Mast cell extracellular trap formation underlies vascular and neural injury and hyperalgesia in sickle cell disease.Life science alliance · 2024Article
- Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?Expert review of hematology · 2024Review
- Article
- Sickle cell disease chronic joint pain: Clinical assessment based on maladaptive central nervous system plasticity.Frontiers in medicine · 2022Review
- Moving Toward a Multimodal Analgesic Regimen for Acute Sickle Cell Pain with Non-Opioid Analgesic Adjuncts: A Narrative Review.Journal of pain research · 2022Review
- Pain in sickle cell disease: current and potential translational therapies.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Heme Causes Pain in Sickle MiceAntioxidants & redox signaling · 2021Article
- Neuropathic pain in sickle cell disease: measurement and management.Hematology. American Society of Hematology. Education Program · 2020Review
- Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease.Journal of clinical medicine · 2020Review
- Integrative approaches to treating pain in sickle cell disease: Pre-clinical and clinical evidence.Complementary therapies in medicine · 2020Review
- Innate immune cells, major protagonists of sickle cell disease pathophysiology.Haematologica · 2020Review
- Substance P modulates electroacupuncture analgesia in humanized mice with sickle cell disease.Journal of pain research · 2019Article
- Mast Cells Induce Blood Brain Barrier Damage in SCD by Causing Endoplasmic Reticulum Stress in the Endothelium.Frontiers in cellular neuroscience · 2019Article
- Mast cell-neural interactions contribute to pain and itch.Immunological reviews · 2018Review
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7 authors.
Funding
Abstract
Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: (i) SCD baseline and controls, and (ii) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean ± standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32·4 ± 11·6 vs. 22·9 ± 7·6, P = 0·0009). SP in SCD pain was higher than baseline (78·1 ± 43·4 vs. 32·4 ± 11·6, P = 0·004). Haemolysis correlated with increased SP: Hb (r = -0·7, P = 0·0002), reticulocyte count (r = 0·61, P = 0·0016), bilirubin (r = 0·68, P = 0·0216), lactate dehydrogenase (r = 0·62, P = 0·0332), aspartate aminotransferase (r = 0·68, P = 0·003). Patients taking hydroxycarbamide had increased SP (β = 29·2, P = 0·007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment.
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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.