ArticlePain2016
Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury.
Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 38 citations in OpenAlex.
- Efficacy of duloxetine and gabapentin in pain reduction in patients with knee osteoarthritis.Clinical rheumatology · 2019Trial
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- The role of voltage-gated calcium channel α2δ-1 in the occurrence and development in myofascial orofacial pain.BMC oral health · 2024Article
- Article
- Pathophysiological roles of thrombospondin-4 in disease development.Seminars in cell & developmental biology · 2024Review
- Article
- Sigma-1 receptor activity in primary sensory neurons is a critical driver of neuropathic pain.Gene therapy · 2022Article
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Neuronal αPflugers Archiv : European journal of physiology · 2020Review
- Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes.The Journal of veterinary medical science · 2020Article
- Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages.Cell death & disease · 2020Article
- Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit αScientific reports · 2019Article
- Article
- Thrombospondin-4 in tissue remodeling.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Getting a handle on CaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Gabapentin prevents synaptogenesis between sensory and spinal cord neurons induced by thrombospondin-4 acting on pre-synaptic CaBritish journal of pharmacology · 2018Article
- Injury-induced maladaptation and dysregulation of calcium channel αBritish journal of pharmacology · 2018Review
- Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation.Annals of the rheumatic diseases · 2017Article
- Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons.Neuropharmacology · 2017Article
- Orai1 and Orai3 Mediate Store-Operated Calcium Entry Contributing to Neuronal Excitability in Dorsal Root Ganglion Neurons.Frontiers in cellular neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Loss of high-voltage-activated (HVA) calcium current (ICa) and gain of low-voltage-activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. During depolarization adequate to activate HVA ICa, TSP4 decreases both N- and L-type ICa and the associated intracellular calcium transient. In contrast, TSP4 increases ICa and the intracellular calcium signal after low-voltage depolarization, which we confirmed is due to ICa through T-type channels. These effects are blocked by gabapentin, which ameliorates neuropathic pain by targeting the α2δ1 calcium subunit. Injury-induced changes of HVA and LVA ICa are attenuated in TSP4 knockout mice. In the neuropathic pain model of spinal nerve ligation, TSP4 application did not further regulate ICa of injured DRG neurons. Taken together, these findings suggest that elevated TSP4 after peripheral nerve injury may contribute to hypersensitivity of peripheral sensory systems by decreasing HVA and increasing LVA in DRG neurons by targeting the α2δ1 calcium subunit. Controlling TSP4 overexpression in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain.
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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.