ArticleThe Journal of biological chemistry2016
Central Mechanisms Mediating Thrombospondin-4-induced Pain States.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Efficacy of duloxetine and gabapentin in pain reduction in patients with knee osteoarthritis.Clinical rheumatology · 2019Trial
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Astrocyte Regulation of Spinal Circuit Function.Journal of neurochemistry · 2026Review
- Expression of thrombospondin-4 in the infrapatellar fat pad and synovial fluid - potential contribution to osteoarthritis pain.Arthritis research & therapy · 2025Article
- Review
- Presynaptic αNeuron · 2025Article
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain.Molecular neurobiology · 2025Review
- The Role of Thrombospondins in Osteoarthritis: from Molecular Mechanisms to Therapeutic Potential.International journal of biological sciences · 2025Review
- The VGCC auxiliary subunit α2δ1 is an extracellular GluA1 interactor and regulates LTP, spatial memory, and seizure susceptibility.bioRxiv : the preprint server for biology · 2024Article
- FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Conditional Knockout of Neurexins Alters the Contribution of Calcium Channel Subtypes to Presynaptic CaCells · 2024Article
- α2δ1-mediated maladaptive sensory plasticity disrupts adipose tissue homeostasis following spinal cord injury.Cell reports. Medicine · 2024Article
- The role of voltage-gated calcium channel α2δ-1 in the occurrence and development in myofascial orofacial pain.BMC oral health · 2024Article
- Pathophysiological roles of thrombospondin-4 in disease development.Seminars in cell & developmental biology · 2024Review
- Neuroprotective Properties of Antiepileptics: What are the Implications for Psychiatric Disorders?Current medicinal chemistry · 2024Review
- EpiPro, a Novel, Synthetic, Activity-Regulated Promoter That Targets Hyperactive Neurons in Epilepsy for Gene Therapy Applications.International journal of molecular sciences · 2023Article
- Voltage-gated calcium channel subunit αFrontiers in molecular neuroscience · 2023Article
- Hevin/Sparcl1 drives pathological pain through spinal cord astrocyte and NMDA receptor signaling.JCI insight · 2022Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Peripheral nerve injury induces increased expression of thrombospondin-4 (TSP4) in spinal cord and dorsal root ganglia that contributes to neuropathic pain states through unknown mechanisms. Here, we test the hypothesis that TSP4 activates its receptor, the voltage-gated calcium channel Cavα2δ1 subunit (Cavα2δ1), on sensory afferent terminals in dorsal spinal cord to promote excitatory synaptogenesis and central sensitization that contribute to neuropathic pain states. We show that there is a direct molecular interaction between TSP4 and Cavα2δ1 in the spinal cord in vivo and that TSP4/Cavα2δ1-dependent processes lead to increased behavioral sensitivities to stimuli. In dorsal spinal cord, TSP4/Cavα2δ1-dependent processes lead to increased frequency of miniature and amplitude of evoked excitatory post-synaptic currents in second-order neurons as well as increased VGlut2- and PSD95-positive puncta, indicative of increased excitatory synapses. Blockade of TSP4/Cavα2δ1-dependent processes with Cavα2δ1 ligand gabapentin or genetic Cavα2δ1 knockdown blocks TSP4 induced nociception and its pathological correlates. Conversely, TSP4 antibodies or genetic ablation blocks nociception and changes in synaptic transmission in mice overexpressing Cavα2δ1 Importantly, TSP4/Cavα2δ1-dependent processes also lead to similar behavioral and pathological changes in a neuropathic pain model of peripheral nerve injury. Thus, a TSP4/Cavα2δ1-dependent pathway activated by TSP4 or peripheral nerve injury promotes exaggerated presynaptic excitatory input and evoked sensory neuron hyperexcitability and excitatory synaptogenesis, which together lead to central sensitization and pain state development.
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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.