Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons

Mol Pain. 2014 Jan 29;10:8. doi: 10.1186/1744-8069-10-8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Pain / metabolism
  • Acute Pain / pathology*
  • Acute Pain / physiopathology
  • Animals
  • Capsaicin
  • Ganglia, Spinal / metabolism
  • HEK293 Cells
  • Humans
  • Kv1.2 Potassium Channel / genetics
  • Kv1.2 Potassium Channel / metabolism*
  • Ligation
  • Male
  • Motor Activity
  • Neuralgia / metabolism
  • Neuralgia / pathology*
  • Neuralgia / physiopathology
  • Neurons, Afferent / metabolism*
  • Neurons, Afferent / pathology
  • Nociception
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / physiopathology
  • Protein Transport
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerves / metabolism
  • Spinal Nerves / pathology
  • Spinal Nerves / physiopathology
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • Kcna2 protein, rat
  • Kv1.2 Potassium Channel
  • RNA, Antisense
  • RNA, Messenger
  • Capsaicin