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  • Oral presentation
  • Open Access

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

BMC Pharmacology20099(Suppl 1):S25

Published: 11 August 2009


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


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.


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.

Authors’ Affiliations

Pharmakologisches Institut, Universitat Heidelberg, Heidelberg, Germany


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


© Luo and Kuner; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.