title: Upregulation of T-type Ca2+ channels in primary sensory neurons in spinal nerve injury.
abstract: METHODS
  Painful behavior testing, whole-cell patch clamp recordings, and PCR analysis were served to test the influence of T-type Ca channels in spinal nerve-injured rats.
  
  
  OBJECTIVE
  To determine the changes of T-type Ca channels in dorsal root ganglion (DRG) neurons of different sizes and the contribution to neuronal firing and painful behavior in neuropathic pain induced by nerve injury.
  
  
  BACKGROUND
  T-type and high-voltage-activated Ca channels play an important role in the transmission of nociceptive signals, especially in neuronal hyperexcitability in neuropathic pain. However, little is known about how nerve injury affects T-type Ca channels in DRG neurons of different sizes.
  
  
  METHODS
  The effect of intrathecal administration of mibefradil in nerve-ligated rats was examined by painful behavior testing and current clamp. The changes of T-type Ca channels in DRG neurons caused by spinal nerve ligation were determined by RT-PCR analysis and voltage clamp.
  
  
  RESULTS
  Spinal nerve injury significantly increased current density of T-type Ca channels in small DRG neurons. In addition, nerve injury significantly increased the percentage of T-type Ca channels in medium and large DRG neurons. Nerve injury significantly increased the mRNA levels of Cav3.2 and Cav3.3 in DRGs. Block of T-type Ca channels on mibefradil administration significantly normalized painful behavior and hyperexcitability in neuronal firing in spinal nerve-injured rats.
  
  
  CONCLUSIONS
  Our study first indicated the upregulation of functional T-type Ca channels in DRG neurons of different sizes and the changes in different subtypes of T-type Ca channels by spinal nerve injury. Considering the effect of blocking T-type Ca channels in painful behavior and abnormal neuronal firing in rats with nerve injury, our results suggest that T-type Ca channels are potential therapeutic targets for the treatment of spinal nerve ligation-induced neuropathic pain.
authors.affiliation: Department of Reproductive Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yue
authors.forename: Lieju
authors.initials: L
authors.lastname: Liu
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000502:physiology*; D005727:Ganglia, Spinal / Q000293:injuries / Q000503:physiopathology; D007278:Injections, Spinal; D008159:Lumbar Vertebrae; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020748:Mibefradil / Q000008:administration & dosage / Q000494:pharmacology; D009437:Neuralgia / Q000503:physiopathology / Q000517:prevention & control; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: C500994:Cacna1g protein, rat; C509958:Cacna1h protein, rat; C583277:Cacna1i protein, rat; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D012333:RNA, Messenger; D020748:Mibefradil