title: Chronic intrathecal infusion of mibefradil, ethosuximide and nickel attenuates nerve ligation-induced pain in rats.
abstract: BACKGROUND
  T-type Ca(2+) channels (TCC) are important for pain transmission, especially the Ca(V)3.2 subtype. In this study, we examined the effects of intrathecal TCC blockers in the L5/6 spinal nerve ligation pain rat model.
  
  
  METHODS
  Under isoflurane anaesthesia, rats received right L5/6 spinal nerve ligation and intrathecal catheters (attached to an infusion pump) were sited. After surgery, saline, mibefradil, ethosuximide or NiCl2 were given intrathecally for seven days. The right hindpaw withdrawal thresholds to von Frey hair stimuli and withdrawal latencies to radiant heat were measured before and once daily for seven days after surgery. Double immunofluorescence and western blotting were used to examine the expression of Ca(V)3.2 in dorsal root ganglion (DRG) and spinal cord.
  
  
  RESULTS
  On post-ligation day seven, rats receiving mibefradil, ethosuximide or NiCl2 had significant higher median withdrawal thresholds (15.0, 10.2, and 10.9 g) and latencies (8.0, 7.6 and 7.6 s) than saline-treated rats (1.6 g and 4.3 s, respectively). Ca(V)3.2 was expressed in parvalbumin(+), IB4(+), CGRP(+) and VR1(+) neurones in DRG and most neurones in spinal dorsal horn. Ca(V)3.2 was up-regulated in the right L5/6 DRG and spinal cord seven days after nerve ligation.
  
  
  CONCLUSIONS
  In this study, we demonstrated that intrathecal TCC blockers attenuate the development of nerve injury-induced mechanical allodynia and thermal hyperalgesia. Our data suggest that continuous intrathecal infusion of TCC or Ca(V)3.2 blockers may be a promising alternative for the management of nerve injury-induced pain.
authors.affiliation: Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: M L
authors.initials: ML
authors.lastname: Tsaur
authors.affiliation: Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan.
authors.forename: S W
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan Department of Pathology, MacKay Memorial Hospital, New Taipei City 252, Taiwan.
authors.forename: T Y
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Hung
authors.affiliation: Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan Department of Anaesthesiology, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: C S
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Y F
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Shiue
authors.affiliation: Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan Department of Anaesthesiology, MacKay Memorial Hospital, Taipei 104, Taiwan MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan jkcheng@usa.net.
authors.forename: J K
authors.initials: JK
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004195:Disease Models, Animal; D005013:Ethosuximide / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D020748:Mibefradil / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy*; D009532:Nickel / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D020748:Mibefradil; D005013:Ethosuximide; D009532:Nickel
keywords: cav3.2; dorsal root ganglion; intrathecal; neuropathic pain; spinal cord