• Stéphanie Ratté and Steven A Prescott.
• Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
• Curr. Opin. Neurobiol. 2016 Feb 1; 36: 31-7.

AbstractNeuropathic pain, which arises from damage to the nervous system, is a major unmet clinical challenge. Reversing the neuronal hyperexcitability induced by nerve damage is a logical treatment strategy but has proven frustratingly difficult. Here, we propose a novel explanation for that difficulty. Changes in several different ion channels are individually sufficient to cause hyperexcitability in primary somatosensory neurons. Despite offering multiple drug targets, this scenario is problematic: if multiple sufficient changes are triggered by nerve injury, then no single change is necessary for hyperexcitability. This so-called degeneracy compromises therapeutic interventions because drug effects on any one ion channel can be circumvented by changes occurring in other ion channels. Overcoming degeneracy demands a more integrative approach to drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

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