Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons.
Voltage-gated potassium (Kv) channels are critical in controlling neuronal excitability and are involved in the induction of neuropathic pain. Therefore, Kv channels might be potential targets for prevention and/or treatment of this disorder. We reported here that a majority of dorsal root ganglion (DRG) neurons were positive for Kv channel alpha subunit Kv1.2. Most of them were large and medium, although there was a variety of sizes. Peripheral nerve injury caused by lumbar (L)5 spinal nerve ligation (SNL) produced a time-dependent reduction in the number of Kv1.2-positive neurons in the ipsilateral L5 DRG, but not in the contralateral L5 DRG. Such reduction was also observed in the ipsilateral L5 DRG on day 7 after sciatic nerve axotomy. Rescuing nerve injury-induced reduction of Kv1.2 in the injured L5 DRG attenuated the development and maintenance of SNL-induced pain hypersensitivity without affecting acute pain and locomotor function. This effect might be attributed to the prevention of SNL-induced upregulation of endogenous Kv1.2 antisense RNA, in addition to the increase in Kv1.2 protein expression, in the injured DRG. Our findings suggest that Kv1.2 may be a novel potential target for preventing and/or treating neuropathic pain.
Longchang
L
Fan
Xiaowei
X
Guan
Wei
W
Wang
Jian-Yuan
JY
Zhao
Hongkang
H
Zhang
Vinod
V
Tiwari
Paul N
PN
Hoffman
Min
M
Li
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. yt211@njms.rutgers.edu.
Yuan-Xiang
YX
Tao
D059787:Acute Pain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002211:Capsaicin; D005727:Ganglia, Spinal / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051663:Kv1.2 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009043:Motor Activity; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D059225:Nociception; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D021381:Protein Transport; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D016372:RNA, Antisense; D012333:RNA, Messenger; D002211:Capsaicin