Silencing the Kir4.1 potassium channel subunit in satellite glial cells of the rat trigeminal ganglion results in pain-like behavior in the absence of nerve injury.
Growing evidence suggests that changes in the ion buffering capacity of glial cells can give rise to neuropathic pain. In the CNS, potassium ion (K+) buffering is dependent on the glia-specific inward rectifying K+ channel Kir4.1. We recently reported that the satellite glial cells that surround primary sensory neurons located in sensory ganglia of the peripheral nervous system also express Kir4.1, whereas the neurons do not. In the present study, we show that, in the rat trigeminal ganglion, the location of the primary sensory neurons for face sensation, specific silencing of Kir4.1 using RNA interference leads to spontaneous and evoked facial pain-like behavior in freely moving rats. We also show that Kir4.1 in the trigeminal ganglion is reduced after chronic constriction injury of the infraorbital nerve. These findings suggests that neuropathic pain can result from a change in expression of a single K+ channel in peripheral glial cells, raising the possibility of targeting Kir4.1 to treat pain in general and particularly neuropathic pain that occurs in the absence of nerve injury.
Vit
Jean-Philippe
JP
Department of Neurosurgery and Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Ohara
Peter T
PT
Bhargava
Aditi
A
Kelley
Kanwar
K
Jasmin
Luc
L
D000818:Animals; D002460:Cell Line; D020868:Gene Silencing / Q000502:physiology; D000882:Haplorhini; D008297:Male; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D027161:Satellite Cells, Perineuronal / Q000166:cytology / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits