title: Transient receptor potential ankyrin 1 ion channel contributes to guarding pain and mechanical hypersensitivity in a rat model of postoperative pain.
abstract: BACKGROUND
  The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed on nociceptive primary afferent nerve fibers. On the distal ending, it is involved in transduction of noxious stimuli, and on the proximal ending (within the spinal dorsal horn), it regulates transmission of nociceptive signals. Here we studied whether the cutaneous or spinal TRPA1 ion channel contributes to mechanical hypersensitivity or guarding, an index of spontaneous pain, in an experimental model of postoperative pain in the rat.
  
  
  METHODS
  A skin plus deep-tissue incision was performed under general anesthesia in the plantar skin of one hind paw, after which the incised skin was closed with sutures. Postoperative pain and hypersensitivity were assessed 24-48 h after the operation. Guarding pain was assessed by scoring the hind-paw position. Mechanical hypersensitivity was assessed with a calibrated series of monofilaments applied to the wound area in the operated paw or the contralateral control paw. Chembridge-5861528, a TRPA1 channel antagonist, was administered intaperitoneally (10-30 mg/kg), intraplantarly (10-30 μg), or intrathecally (10 μg) in attempts to suppress guarding and hypersensitivity.
  
  
  RESULTS
  Intraperitoneal or ipsi- but not contralateral intraplantar treatment with Chembridge-5861528 reduced mechanical hypersensitivity and guarding in the operated limb. Intrathecal treatment attenuated hypersensitivity but not guarding. Intraplantar Chembridge-5861528 suppressed preferentially mechanical hyperalgesia and intrathecal Chembridge-5861528 tactile allodynia.
  
  
  CONCLUSIONS
  The TRPA1 channel in the skin contributes to sustained as well noxious mechanical stimulus-evoked postoperative pain, whereas the spinal TRPA1 channel contributes predominantly to innocuous mechanical stimulus-evoked postoperative pain.
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.forename: Mari
authors.initials: M
authors.lastname: Karimaa
authors.forename: Timo
authors.initials: T
authors.lastname: Korjamo
authors.forename: Ari
authors.initials: A
authors.lastname: Koivisto
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000209:etiology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010091:Oximes / Q000494:pharmacology; D010149:Postoperative Pain / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology
chemical_list: C560402:A 967079; D006993:Hypnotics and Sedatives; D010091:Oximes; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat