ArticleThe Journal of clinical investigation2022
The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 39 citations in OpenAlex.
- Development of clinical-radiological prediction models to prioritizeJournal of thoracic disease · 2026Article
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Induction of human pruriceptors from pluripotent stem cells via transcription factors.Stem cell reports · 2026Article
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Functional expression of the T-type Cav3.2 calcium channel in female and male human dorsal root ganglion neurons.Brain : a journal of neurology · 2026Article
- Plasma ALKAL2 levels are associated with coronary atherosclerosis in patients with type 2 diabetes mellitus.Cardiovascular diabetology · 2025Article
- A nociceptive amygdala-striatal pathway modulating affective-motivational pain.Science advances · 2025Article
- Neuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification and Mapping of Human Lymph Node Stromal Cell Subsets by Combining Single-Cell RNA Sequencing with Spatial Transcriptomics.European journal of immunology · 2025Article
- AlkCell communication and signaling : CCS · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Whole Exome Sequencing Reveals Novel Genetic Variants Associated with Atrial Septal Defect in a Tibetan Patient Cohort.Pharmacogenomics and personalized medicine · 2025Article
- Article
- Platelet-derived Growth Factor Receptor-α Induces Contraction Knots and Inflammatory Pain-like Behavior in a Rat Model of Myofascial Trigger Points.Anesthesiology · 2024Article
- Cytokines reprogram airway sensory neurons in asthma.bioRxiv : the preprint server for biology · 2024Article
- 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.medRxiv : the preprint server for health sciences · 2024Article
- Induction of antiviral interferon-stimulated genes by neuronal STING promotes the resolution of pain in mice.The Journal of clinical investigation · 2024Article
- Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review.Biomolecules · 2023Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase known for its oncogenic potential that is involved in the development of the peripheral and central nervous system. ALK receptor ligands ALKAL1 and ALKAL2 were recently found to promote neuronal differentiation and survival. Here, we show that inflammation or injury enhanced ALKAL2 expression in a subset of TRPV1+ sensory neurons. Notably, ALKAL2 was particularly enriched in both mouse and human peptidergic nociceptors, yet weakly expressed in nonpeptidergic, large-diameter myelinated neurons or in the brain. Using a coculture expression system, we found that nociceptors exposed to ALKAL2 exhibited heightened excitability and neurite outgrowth. Intraplantar CFA or intrathecal infusion of recombinant ALKAL2 led to ALK phosphorylation in the lumbar dorsal horn of the spinal cord. Finally, depletion of ALKAL2 in dorsal root ganglia or blocking ALK with clinically available compounds crizotinib or lorlatinib reversed thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury, respectively. Overall, our work uncovers the ALKAL2/ALK signaling axis as a central regulator of nociceptor-induced sensitization. We propose that clinically approved ALK inhibitors used for non-small cell lung cancer and neuroblastomas could be repurposed to treat persistent pain conditions.
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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.