title: Adenosine triphosphate-sensitive potassium channel blockers attenuate the antiallodynic effect of R-PIA in neuropathic rats.
abstract: BACKGROUND
  Nerve injury can generate neuropathic pain. The accompanying mechanical allodynia may be reduced by the intrathecal administration of adenosine. The neuroprotective effects of adenosine are mediated by the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel. We assessed the relationship between the adenosine A1 receptor agonist, N⁶-(R)-phenylisopropyl adenosine (R-PIA), and K(ATP) channels to determine whether the antiallodynic effects of R-PIA are also mediated through K(ATP) channels in a rat nerve ligation injury model of neuropathic pain.
  
  
  METHODS
  Mechanical allodynia was induced by tight ligation of the left lumbar fifth and sixth spinal nerves. Mechanical allodynia in the left hindpaw was evaluated using von Frey filaments to measure withdrawal thresholds. R-PIA (0.5, 1, or 2 μg) was administered intrathecally to induce antiallodynia. We assessed whether pretreatment with the K(ATP) channel blockers glibenclamide or 5-hydroxydecanoate reversed the antiallodynic effect of R-PIA. Also, we evaluated whether diazoxide, a K(ATP) channel opener, had an antiallodynic effect and promoted the antiallodynic effect of R-PIA. Lastly, we investigated whether the voltage-activated K channel blocker 4-aminopyridine attenuated the effect of R-PIA.
  
  
  RESULTS
  Intrathecal R-PIA produced maximal antiallodynia at 2 μg (P < 0.05). Intrathecal pretreatment with glibenclamide and intraperitoneal pretreatment 5-hydroxydecanoate significantly reduced the antiallodynic effect of R-PIA. Diazoxide produced an antiallodynic effect and also enhanced the antiallodynic action of R-PIA. 4-Aminopyridine had no effect on the antiallodynic action of R-PIA.
  
  
  CONCLUSIONS
  The antiallodynic effects of adenosine A1 receptor stimulation may be related to K(ATP) channel activity in a rat model of nerve ligation injury.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, 138-736, Korea. sjinwoo@hotmail.com
authors.forename: Jun-Gol
authors.initials: JG
authors.lastname: Song
authors.forename: Kyung Don
authors.initials: KD
authors.lastname: Hahm
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Kim
authors.forename: Jeong Gil
authors.initials: JG
authors.lastname: Leem
authors.forename: Chung
authors.initials: C
authors.lastname: Lee
authors.forename: Sung Moon
authors.initials: SM
authors.lastname: Jeong
authors.forename: Pyung Hwan
authors.initials: PH
authors.lastname: Park
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Shin
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects
chemical_list: D026902:Potassium Channel Blockers; C047235:N-(1-methyl-2-phenylethyl)adenosine; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D000241:Adenosine; D005905:Glyburide