ArticlePloS one2016
Duloxetine Inhibits Microglial P2X4 Receptor Function and Alleviates Neuropathic Pain after Peripheral Nerve Injury.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 62 citations in OpenAlex.
- Duloxetine as a gut-brain axis modulator in irritable bowel syndrome: neuroimmune, microbiota, and pharmacogenomic perspectives.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- BDNF-TrkB Signaling Engages a Src Family Kinase-Pannexin 1 Pathway During the Onset of Sustained Mechanical Hyperalgesia.International journal of molecular sciences · 2026Article
- The Effect of Duloxetine on Fusion in Rats Undergoing Posterolateral Spinal Fusion.Journal of clinical medicine · 2026Article
- P2X4 Receptor Antagonist Ameliorates Ocular Pain in Rats After Lacrimal Gland Removal.Translational vision science & technology · 2025Article
- Spinal P2X4 Receptors Involved in Visceral Hypersensitivity of Neonatal Maternal Separation Rats.Purinergic signalling · 2023Article
- Neuropathic pain: Mechanisms and therapeutic strategies.Frontiers in cell and developmental biology · 2023Review
- Structure-Activity Relationship and Neuroprotective Activity of 1,5-Dihydro-2Journal of medicinal chemistry · 2022Article
- MiR-106b-5p Attenuates Neuropathic Pain by Regulating the P2X4 Receptor in the Spinal Cord in Mice.Journal of molecular neuroscience : MN · 2022Article
- The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target.International journal of molecular sciences · 2022Review
- The Role of Microglial Purinergic Receptors in Pain Signaling.Molecules (Basel, Switzerland) · 2022Review
- Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19.Immunopharmacology and immunotoxicology · 2021Review
- Article
- Review
- Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities.Frontiers in neuroscience · 2021Review
- Role of microglia and P2X4 receptors in chronic pain.Pain reports · 2021Review
- Contribution of P2X4 Receptors to CNS Function and Pathophysiology.International journal of molecular sciences · 2020Review
- Resolving the Ionotropic P2X4 Receptor Mystery Points Towards a New Therapeutic Target for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Pharmacological and genetic characterisation of the canine P2X4 receptor.British journal of pharmacology · 2020Article
- Acetaminophen combined with tramadol is more effective than acetaminophen or tramadol to reduce neuropathic root pain: an experimental study with application of nucleus pulposus in a rat model.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020Article
- Relationship Between Pain Alleviation and Disease-specific Health-related Quality of Life Measures in Patients With Chronic Low Back Pain Receiving Duloxetine: Exploratory Post Hoc Analysis of a Japanese Phase 3 Randomized Study.Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R. In primary cultured microglial cells, duloxetine also inhibited P2X4R-, but not P2X7R-, mediated responses. Moreover, intrathecal administration of duloxetine in a model of neuropathic pain produced a reversal of nerve injury-induced mechanical allodynia, a cardinal symptom of neuropathic pain. In rats that were pretreated with a serotonin-depleting agent and a noradrenaline neurotoxin, the antiallodynic effect of duloxetine was reduced, but still remained. Based on these results, we suggest that, in addition to duloxetine's primary inhibitory action on serotonin and noradrenaline transporters, an inhibitory effect on P2X4R may be involved at least in part in an antiallodynic effect of intrathecal duloxetine in a model of neuropathic pain.
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