• Psychopharmacology · Jan 2008

    The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain.

    • Xiao-Wei Dong, Yuping Jia, Sherry X Lu, Xiaoping Zhou, Mary Cohen-Williams, Robert Hodgson, Huiqing Li, and Tony Priestley.
    • Department of Neurobiology, Schering-Plough Research Institute, K-15-2-2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. zoe.dong@spcorp.com
    • Psychopharmacology (Berl.). 2008 Jan 1;195(4):559-68.

    RationaleFluphenazine is a potent antipsychotic drug used to treat schizophrenia and other psychotic symptoms. Its clinical benefit is mainly mediated by the antagonism of dopamine D2 receptors. We have recently discovered, however, that fluphenazine is also a potent sodium channel blocker, a property that may offer additional therapeutical indications, including analgesia.ObjectivesThe present study sought to determine the analgesic effect of fluphenazine on neuropathic pain in animal models.MethodsThe effect of fluphenazine on mechanical allodynia was assessed in three animal neuropathic pain models, including spinal nerve ligation, chronic constriction nerve injury (CCI), and sural-spared sciatic nerve injury models.ResultsSystemic fluphenazine effectively attenuated mechanical allodynia in all three rat neuropathic pain models at doses (0.03-0.3 mg/kg) that approximate those used in rodent models of psychosis. In parallel with its in vivo antiallodynic effect, fluphenazine (3-30 microM) effectively suppressed the ectopic discharges in injured afferent fibers without affecting the propagation of action potentials evoked by electrical nerve stimulation in an ex vivo dorsal root ganglia (DRG)-nerve preparation excised from CCI rats. Furthermore, similar concentrations of fluphenazine significantly blocked sodium channels in DRG neurons.ConclusionsThe inhibitory action of fluphenazine on ectopic afferent discharges may be due to its ability to block voltage-gated sodium channels, and this may also provide a mechanistic basis for the drug's antiallodynic effect in animal models of neuropathic pain. In summary, our study demonstrates that the classic antipsychotic drug fluphenazine has antiallodynic properties in multiple rodent models of nerve injury-induced neuropathic pain.

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