title: The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain.
abstract: BACKGROUND
  Fluphenazine 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.
  
  
  OBJECTIVE
  The present study sought to determine the analgesic effect of fluphenazine on neuropathic pain in animal models.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Systemic 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.
  
  
  CONCLUSIONS
  The 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.
authors: Department of Neurobiology, Schering-Plough Research Institute, K-15-2-2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. zoe.dong@spcorp.com
authors: Xiao-Wei
authors: XW
authors: Dong
authors: Yuping
authors: Y
authors: Jia
authors: Sherry X
authors: SX
authors: Lu
authors: Xiaoping
authors: X
authors: Zhou
authors: Mary
authors: M
authors: Cohen-Williams
authors: Robert
authors: R
authors: Hodgson
authors: Huiqing
authors: H
authors: Li
authors: Tony
authors: T
authors: Priestley
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005476:Fluphenazine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009408:Nerve Compression Syndromes / Q000503:physiopathology; D009437:Neuralgia / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D012585:Sciatica / Q000503:physiopathology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013127:Spinal Nerves / Q000187:drug effects / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D015222:Sodium Channels; D005476:Fluphenazine