title: Afferent hyperexcitability in neuropathic pain and the inconvenient truth about its degeneracy.
abstract: Neuropathic 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.
authors.affiliation: Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ratté
authors.affiliation: Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada. Electronic address: steve.prescott@sickkids.ca.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Prescott
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology*; D059350:Chronic Pain / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D007473:Ion Channels / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology
chemical_list: D007473:Ion Channels