title: The effect of intrathecal administration TRPA1 antagonists in a rat model of neuropathic pain.
abstract: BACKGROUND
  The fact that transient receptor potential ankyrin 1 (TRPA1) on the peripheral terminals could attenuate hyperalgesia is widely accepted, but the effect of spinal TRPA1 in the modulation of hyperalgesia has not been fully demonstrated. In the present study, we investigated the effect of intrathecal (i.t.) administration TRPA1 antagonists on chronic pain and expression of TRPA1 and phosphorylation N-methyl-D-aspartate receptor 2B subunit (p-NR2B) in the spinal cord with chronic compression of the dorsal root ganglia (CCD) in rats.
  
  
  METHODS
  The study was conducted in 2 parts. Part 1: Sixteen rats were divided into 2 groups (n = 8 each): a sham group and CCD group. Paw withdrawal mechanical thresholds (PWMT) were measured at baseline and 1, 3, 7, 10, 14, and 21 days after CCD. Sixteen other rats were used to evaluate expression of TRPA1 and p-NR2B in spinal cord on the seventh and 14th days after CCD; Western blotting was used to evaluate expression levels (n = 4 each). Part 2: 40 rats were divided into 5 groups (n = 8 each): CCD group, CCD + Vehicle group, CCD + HC-030031(10 μg, i.t.) group, CCD + HC-030031(25 μg, i.t.) group, and CCD + HC-030031(50 μg, i.t.) group. PWMTs were measured at baseline and 0.5, 1, 2, 4, and 6 hours after i.t. HC-030031 on the third, seventh, 10th, and 14th days after CCD. Another 48 rats were used to evaluate expression of TRPA1 and p-NR2B in spinal cord 2 hours after injection on the seventh and 14th days after CCD in groups CCD, CCD + Vehicle, and CCD+ HC-030031(50 μg, i.t.) using Western blotting (n = 4 each).
  
  
  RESULTS
  Compared with the sham group, PWMT was significantly decreased, and protein expression of TRPA1 and p-NR2B were upregulated, in spinal cord on the seventh and 14th days after CCD operation. TRPA1 antagonists (HC-030031, 50 μg, i.t.) increased the PWMT after CCD and downregulated the protein level of TRPA1 and p-NR2B in spinal cord at 2 hours after the injection on the seventh and 14th days after CCD.
  
  
  CONCLUSIONS
  These data demonstrated that the i.t. administration of TRPA1 antagonists could attenuate neuropathic pain in CCD rats, and this effect could be partially reduced by p-NR2B receptor expression in spinal cord.
authors.affiliation: From the Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; C121001:NR2B NMDA receptor; D011687:Purines; D016194:Receptors, N-Methyl-D-Aspartate; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat