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Presynaptic cGMP-dependent protein kinase-I mediates synaptic potentiation in spinal amplification of pain

Background

Activity-dependent facilitation of pain is functionally linked to plasticity at synapses between peripheral sensory afferents and spinal projection neurons. However, the underlying cellular and molecular mechanisms are not well-understood [1]. We observed that long-term potentiation at these synapses involves a presynaptic mechanism comprising activity-induced decrease in synaptic failures. This process involves activation of the cGMP-dependent protein kinase-I (PKG-I) in presynaptic terminals of nociceptive afferents and potentiation of vesicular transmitter release via modulation of IP3 receptors and myosin light chains. Mice lacking PKG-I specifically in nociceptors did not develop spinal long-term potentiation and showed marked defects in pathological pain in vivo.

Conclusion

Our results reveal a causal link between PKG-I-dependent presynaptic modulation of transmitter release, long-term potentiation at spinal synapses and the induction of pathological pain.

References

  1. 1.

    Woolf CJ, Salter MW: Neuronal plasticity: Increasing the gain in pain. Science. 2000, 288: 1765-1768. 10.1126/science.288.5472.1765.

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Correspondence to Rohini Kuner.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Luo, C., Kuner, R. Presynaptic cGMP-dependent protein kinase-I mediates synaptic potentiation in spinal amplification of pain. BMC Pharmacol 9, S25 (2009). https://doi.org/10.1186/1471-2210-9-S1-S25

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Keywords

  • Myosin Light Chain
  • Transmitter Release
  • Presynaptic Terminal
  • Spinal Projection
  • Sensory Afferents