ArticlePloS one2018
Augmenting the antinociceptive effects of nicotinic acetylcholine receptor activity through lynx1 modulation.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- An Ascending Excitatory Circuit from the Dorsal Raphe for Sensory Modulation of Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A novel anxiety-associated SNP identified inFrontiers in behavioral neuroscience · 2024Article
- Comparison of Conformations and Interactions with Nicotinic Acetylcholine Receptors forInternational journal of molecular sciences · 2023Article
- α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain.International journal of molecular sciences · 2023Review
- RETRACTED: Activating SIRT-1 Signalling with the Mitochondrial-CoQ10 Activator Solanesol Improves Neurobehavioral and Neurochemical Defects in Ouabain-Induced Experimental Model of Bipolar Disorder.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Expression and Roles of Lynx1, a Modulator of Cholinergic Transmission, in Skeletal Muscles and Neuromuscular Junctions in Mice.Frontiers in cell and developmental biology · 2022Article
- Differential Expression Patterns of Lynx Proteins and Involvement of Lynx1 in Prepulse Inhibition.Frontiers in behavioral neuroscience · 2021Article
- Modulation of cholinergic activity through lynx prototoxins: Implications for cognition and anxiety regulation.Neuropharmacology · 2020Review
- Dynamics and Interactions of GPI-Linked lynx1 Protein with/without Nicotinic Acetylcholine Receptor in Membrane Bilayers.The journal of physical chemistry. B · 2020Article
- Bisphenol A Regulates Sodium Ramp Currents in Mouse Dorsal Root Ganglion Neurons and Increases Nociception.Scientific reports · 2019Article
- Article
- Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes.Frontiers in pharmacology · 2019Review
- Pain-Related PANoptosis Gene Signature Predicts Prognosis and Guides Therapy in Oral Squamous Cell Carcinoma.Technology in cancer research & treatmentArticle
- Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function.eNeuroArticle
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) of the cholinergic system have been linked to antinociception, and therefore could be an alternative target for pain alleviation. nAChR activity has been shown to be regulated by the nicotinic modulator, lynx1, which forms stable complexes with nAChRs and has a negative allosteric action on their function. The objective in this study was to investigate the contribution of lynx1 to nicotine-mediated antinociception. Lynx1 contribution was investigated by mRNA expression analysis and electrophysiological responses to nicotine in the dorsal raphe nucleus (DRN), a part of the pain signaling pathway. In vivo antinociception was investigated in a test of nociception, the hot-plate analgesia assay with behavioral pharmacology. Lynx1/α4β2 nAChR interactions were investigated using molecular dynamics computational modeling. Nicotine evoked responses in serotonergic and GABAergic neurons in the DRN are augmented in slices lacking lynx1 (lynx1KO). The antinociceptive effect of nicotine and epibatidine is enhanced in lynx1KO mice and blocked by mecamylamine and DHβE. Computer simulations predict preferential binding affinity of lynx1 to the α:α interface that exists in the stoichiometry of the low sensitivity (α4)3(β2)2 nAChRs. Taken together, these data point to a role of lynx1 in mediating pain signaling in the DRN through preferential affinity to the low sensitivity α4β2 nAChRs. This study suggests that lynx1 is a possible alternative avenue for nociceptive modulation outside of opioid-based strategies.
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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.