Journal
PAIN
Volume 138, Issue 3, Pages 537-545Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2008.01.031
Keywords
neuropathic pain; axotomy; potassium channels; M-currents; primary afferents; peripheral nerve
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Funding
- Spanish Ministry of Education and Science [SAF 2006-03044]
- Madrid Regional Government [S-SAL-0305-2006]
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The M-current hits been proposed as a potential target for analgesia Under neuropathic pain conditions. M-currents and/or their molecular correlates, KCNQ proteins, have been demonstrated in key elements of the nociceptive system including spinal and dorsal root ganglion neurons. Here we demonstrate that retigabine, a selective KCNQ channel opener, applied at neuromatose endings modulates the excitability of axotomized fibres inhibiting ectopic discharges. Responses to mechanical and chemical stimulation were obtained from intact and previously axotomized A delta- and C-fibres using in vitro preparations and extracellular electrophysiological recording techniques. Application of retigabine (10 mu M) produced all estimated similar to 80% reduction in the number of discharges produced by mechanical and chemical stimulation of most axotomized fibres tested (24/27). The electrical threshold of stimuli applied to the neuroma Was found to increase in the presence of retigabine (+17.5 +/- 2.3%) and to decrease in the presence of it high potassium medium (-16.5 +/- 3.7%). This indicates that retigabine produces a hyperpolarization and it Subsequent reduction of the excitability in aberrant sensory endings. Application of XE-991 (10 mu M), a KCNQ channel blocker, had no effect on responses to stimulation of the neuroma but blocked the effects of retigabine indicating it specific involvement of KCNQ channels. In contrast to the strong effects oil ectopic discharges, retigabine did not change responses to stimulation recorded from intact receptors. Results indicate that KCNQ channel opening at axotomized endings may constitute a novel and selective mechanism for modulation of some neuropathic pain symptoms. (C) 2008 International Association for the Study or Pain. Published by Elsevier B.V. All rights reserved.
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