ArticleMolecular pain2009
Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief.
Article in Molecular pain, 2009. 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, 128 citations in OpenAlex.
- Piperazine-based P2X4 receptor antagonists.Archiv der Pharmazie · 2025Article
- Microglia in Neuropathic Pain.Advances in neurobiology · 2024Review
- Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells.Science signaling · 2023Article
- Long non-coding RNA MSTRG.81401 short hairpin RNA relieves diabetic neuropathic pain and behaviors of depression by inhibiting P2X4 receptor expression in type 2 diabetic rats.Purinergic signalling · 2023Article
- Article
- Structure-Activity Relationship and Neuroprotective Activity of 1,5-Dihydro-2Journal of medicinal chemistry · 2022Article
- The Role of ATP Receptors in Pain Signaling.Neurochemical research · 2022Review
- 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
- Profiling Differential Effects of 5 Selective Serotonin Reuptake Inhibitors on TLRs-Dependent and -Independent IL-6 Production in Immune Cells Identifies Fluoxetine as Preferred Anti-Inflammatory Drug Candidate.Frontiers in pharmacology · 2022Article
- Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19.Immunopharmacology and immunotoxicology · 2021Review
- Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice.Behavioural brain research · 2021Article
- Contribution of P2X4 receptor in pain associated with rheumatoid arthritis: a review.Purinergic signalling · 2021Review
- Nociceptive signaling of P2X receptors in chronic pain states.Purinergic signalling · 2021Review
- Role of microglia and P2X4 receptors in chronic pain.Pain reports · 2021Review
- P2YInternational journal of molecular sciences · 2020Article
- 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
- Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants-Possible Involvement in Pain Alleviation.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Paroxetine suppresses reactive microglia-mediated but not lipopolysaccharide-induced inflammatory responses in primary astrocytes.Journal of neuroinflammation · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain.
resultsAntidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 microM and 1.87 microM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine.
conclusionThese results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part via their inhibitory effects on P2X4 receptors.
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