Ako Kato

Publications (2)35.92 Total impact

• Article: Endocannabinoid-dependent plasticity at spinal nociceptor synapses.

  Ako Kato, Pradeep Punnakkal, Alejandro Javier Pernía-Andrade, Carolin von Schoultz, Salim Sharopov, Rita Nyilas, István Katona, Hanns Ulrich Zeilhofer
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  ABSTRACT: Key points  Synaptic plasticity between primary nociceptors and second order dorsal horn neurons serves key roles in pain and analgesia  A contribution of NMDA receptors to long-term potentiation and long-term depression at these synapses has been demonstrated before, but much less is known about a possible role of endocannabinoids and cannabinoid (CB)(1) receptors.  Here we show that CB(1) receptors residing on the spinal terminals of primary nociceptors critically contribute to an NMDA receptor-independent form of long-term depression at these synapses, which requires simultaneous pre- and postsynaptic activity.  A similar long-lasting depression of nociceptive signal transmission can also be obtained with application of CB(1) receptor agonists in the presence of presynaptic stimulation alone.  These findings identify a previously unknown form of long-term depression at spinal nociceptor synapses, which may be important for our understanding of pain-related neural plasticity and analgesic actions of CB(1) receptor agonists.
  The Journal of Physiology 07/2012; 590(Pt 19):4717-33. · 4.72 Impact Factor
• Article: Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization.

  Alejandro J Pernía-Andrade, Ako Kato, Robert Witschi, Rita Nyilas, István Katona, Tamás F Freund, Masahiko Watanabe, Jörg Filitz, Wolfgang Koppert, Jürgen Schüttler, Guangchen Ji, Volker Neugebauer, Giovanni Marsicano, Beat Lutz, Horacio Vanegas, Hanns Ulrich Zeilhofer
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  ABSTRACT: Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways that reduce synaptic inhibition in inflammatory and neuropathic pain states have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C-fiber) input to the spinal dorsal horn. We found that endocannabinoids, produced upon strong nociceptive stimulation, activated type 1 cannabinoid (CB1) receptors on inhibitory dorsal horn neurons to reduce the synaptic release of gamma-aminobutyric acid and glycine and thus rendered nociceptive neurons excitable by nonpainful stimuli. Our results suggest that spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain-controlling circuits.
  Science 09/2009; 325(5941):760-4. · 31.20 Impact Factor