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dc.contributor.authorTsantoulas, Christoforosen
dc.contributor.authorZhu, Lanen
dc.contributor.authorShaifta, Yasinen
dc.contributor.authorGrist, Johnen
dc.contributor.authorWard, Jeremy P. T.en
dc.contributor.authorRaouf, Raminen
dc.contributor.authorMichael, G. J.en
dc.contributor.authorMcMahon, Stephen B.en
dc.date.accessioned2015-04-30T13:33:03Z
dc.date.available2015-04-30T13:33:03Z
dc.date.issued2012-02-19
dc.identifier.citationTsantoulas, C. et al. (2012) Sensory Neuron Downregulation of the Kv9.1 Potassium Channel Subunit Mediates Neuropathic Pain following Nerve Injury. The Journal of Neuroscience, 32 (48), pp. 17502-17513en
dc.identifier.issn1529-2401
dc.identifier.urihttp://hdl.handle.net/2086/10925
dc.description.abstractChronic neuropathic pain affects millions of individuals worldwide, is typically long-lasting, and remains poorly treated with existing therapies. Neuropathic pain arising from peripheral nerve lesions is known to be dependent on the emergence of spontaneous and evoked hyperexcitability in damaged nerves. Here, we report that the potassium channel subunit Kv9.1 is expressed in myelinated sensory neurons, but is absent from small unmyelinated neurons. Kv9.1 expression was strongly and rapidly downregulated following axotomy, with a time course that matches the development of spontaneous activity and pain hypersensitivity in animal models. Interestingly, siRNA-mediated knock-down of Kv9.1 in naive rats led to neuropathic pain behaviors. Diminished Kv9.1 function also augmented myelinated sensory neuron excitability, manifested as spontaneous firing, hyper-responsiveness to stimulation, and persistent after-discharge. Intracellular recordings from ex vivo dorsal root ganglion preparations revealed that Kv9.1 knock-down was linked to lowered firing thresholds and increased firing rates under physiologically relevant conditions of extracellular potassium accumulation during prolonged activity. Similar neurophysiological changes were detected in animals subjected to traumatic nerve injury and provide an explanation for neuropathic pain symptoms, including poorly understood conditions such as hyperpathia and paresthesias. In summary, our results demonstrate that Kv9.1 dysfunction leads to spontaneous and evoked neuronal hyperexcitability in myelinated fibers, coupled with development of neuropathic pain behaviors.en
dc.language.isoenen
dc.publisherSciety for Neuroscienceen
dc.subjectchronic neuropathic painen
dc.subjectdorsal root ganglionen
dc.subjectdorsal rooten
dc.subjectvoltage gated potassium channelen
dc.subjectKv9.1en
dc.subjectelectrophysiologyen
dc.titleSensory Neuron Downregulation of the Kv9.1 Potassium Channel Subunit Mediates Neuropathic Pain following Nerve Injuryen
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1523/JNEUROSCI.3561-12.2012
dc.peerreviewedYesen
dc.funderWellcome Trust-funded London Pain Consortiumen
dc.funderEPSRC (Engineering and Physical Sciences Research Council)en
dc.projectidRG53462en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en


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