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.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Song JG,Hahm KD,Kim YK,Leem JG,Lee C,Jeong SM,Park PH,Shin JW

doi

10.1213/ANE.0b013e318212b833

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

1494-9

issue

6

eissn

0003-2999

issn

1526-7598

pii

ANE.0b013e318212b833

journal_volume

112

pub_type

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