1. Neuroscience
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Neuropathic Pain: The pros and cons of degeneracy

  1. Jean-Marc Goaillard  Is a corresponding author
  2. Martial A Dufour
  1. Inserm (Inserm UMR_S 1072) and Aix Marseille University, France
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Cite this article as: eLife 2014;3:e02615 doi: 10.7554/eLife.02615
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Multiple pathways to switch between normal excitability and hyperexcitability in a neuron.

Primary afferent neurons can display a normal excitability profile, characterized by the firing of a single action potential (blue trace) in response to a current step, or a ‘neuropathic’ hyperexcitability profile, characterized by the repetitive firing of action potentials in response to the same stimulus (red trace). Ratté et al. have found that the switch between these two profiles occurs when a tipping point is crossed, and this transition can be induced by varying the sodium (horizontal axis) and potassium conductances (vertical). For instance (left part of the graph), decreasing the potassium conductance (1), increasing the sodium conductance (2) or applying both changes simultaneously (3) induces the transition from normal to neuropathic behaviour, while increasing both conductances (4) preserves a normal excitability profile. Conversely, reversing the neuropathic profile can be achieved by increasing the potassium conductance (5), decreasing the sodium conductance (6) or applying both changes simultaneously (7). Note that, for conductance modifications of the same magnitude (arrows 5, 6 and 7), concerted changes in both conductances are much more efficient in reversing the neuropathic phenotype: the purple squares reached with arrows 5 and 6 are much closer to the tipping point than the blue square reached with arrow 7. This may explain why drugs targeting single ion channels are less efficient at treating neuropathic pain.

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