Participation of K_ATP Channels in the Antinociceptive Effect of Pregabalin in Rat Formalin Test
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background:Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-Ca^2＋- channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods:IT PE-10 catheters were implanted in male Sprague-Dawley rats (250−300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) 20 ml (CON group); pregabalin 0.3, 1, 3 and 10 mg in NS 10 ml (PGB group); glibenclamide 100 mg in DMSO 5 ml with pregabalin 0.3, 1, 3 and 10 mg in NS 5 ml (GBC group). All the drugs were flushed with NS 10 ml. Immunohistochemistry for the KATP channel was done with a different set of rats divided into naïve, NS and PGB groups. Results:IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the KATP channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions:The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the K_ATP channel. However, pregabalin did not induce KATP channel expression in the spinal cord dorsal horn. (Korean J Pain 2011; 24: 131-136)
Abstract
Background:Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-Ca^2＋- channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods:IT PE-10 catheters were implanted in male Sprague-Dawley rats (250−300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) 20 ml (CON group); pregabalin 0.3, 1, 3 and 10 mg in NS 10 ml (PGB group); glibenclamide 100 mg in DMSO 5 ml with pregabalin 0.3, 1, 3 and 10 mg in NS 5 ml (GBC group). All the drugs were flushed with NS 10 ml. Immunohistochemistry for the KATP channel was done with a different set of rats divided into naïve, NS and PGB groups. Results:IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the KATP channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions:The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the K_ATP channel. However, pregabalin did not induce KATP channel expression in the spinal cord dorsal horn. (Korean J Pain 2011; 24: 131-136)
참고문헌 (23)
- Beydoun A, "Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy", Neurology, 64, pp.475~480 (2005)
- Yaksh TL, "Calcium channels as therapeutic targets in neuropathic pain", J Pain, 7(1), pp.S13~S30 (2006)
- Joshi I, "Pregabalin action at a model synapse: binding to presynaptic calcium channel alpha2-delta subunit reduces neurotransmission in mice", Eur J Pharmacol, 553, pp.82~88 (2006)
- Dooley DJ, "Ca2＋ channel alpha2delta ligands: novel modulators of neurotransmission", Trends Pharmacol Sci, 28, pp.75~82 (2007)
- Bauer CS, "A new look at calcium channel α2δ subunits", Curr Opin Neurobiol, 20, pp.563~571 (2010)
- Quintero JE, "Amperometric measurement of glutamate release modulation by gabapentin and pregabalin in rat neocortical slices: role of voltage-sensitive Ca2+ alpha2delta-1 subunit", J Pharmacol Exp Ther, 338, pp.240~245 (2011)
- McClelland D, "A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats", BMC Pharmacol, 4, pp.14~ (2004)
- Ocaña M, "Potassium channels and pain: present realities and future opportunities", Eur J Pharmacol, 500, pp.203~219 (2004)
- Marker CL, "Spinal G-protein- gated potassium channels contribute in a dose-dependent manner to the analgesic effect of mu- and delta- but not kappa-opioids", J Neurosci, 25, pp.3551~3559 (2005)
- Seward E, "Mu-opioid-receptor- mediated inhibition of the N-type calcium-channel current", Proc Biol Sci, 244, pp.129~135 (1991)
- Mixcoatl-Zecuatl, "Effect of K＋ channel modulators on the antiallodynic effect of gabapentin", Eur J Pharmacol, 484, pp.201~208 (2004)
- Yaksh TL, "Chronic catheterization of the spinal subarachnoid space", Physiol Behav, 17, pp.1031~1036 (1976)
- Reshef A, "Opening of ATP- sensitive potassium channels by cromakalim confers tolerance against chemical ischemia in rat neuronal cultures", Neurosci Lett, 250, pp.111~114 (1998)
- Soares AC, "Activation of ATP-sensitive K(＋) channels: mechanism of peripheral antinociceptive action of the nitric oxide donor, sodium nitroprusside", Eur J Pharmacol, 400, pp.67~71 (2000)
- Fehrenbacher JC, "Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C", Pain, 105, pp.133~141 (2003)
- Zhang J, "Efficacy of pregabalin in acute postoperative pain: a meta-analysis", Br J Anaesth, 106, pp.454~462 (2011)
- Fink K, "Inhibition of neuronal Ca(2＋) influx by gabapentin and pregabalin in the human neocortex", Neuropharmacology, 42, pp.229~236 (2002)
- Huang CW, "The opening effect of pregabalin on ATP-sensitive potassium channels in differentiated hippocampal neuron-derived H19-7 cells", Epilepsia, 47, pp.720~726 (2006)
- Mixcoatl-Zecuatl T, "The nitric oxide-cyclic GMP-protein kinase G-K＋ channel pathway participates in the antiallodynic effect of spinal gabapentin", Eur J Pharmacol, 531, pp.87~95 (2006)
- Soares AC, "Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP-sensitive K(＋) channels in the rat PGE2-induced hyperalgesic paw", Br J Pharmacol, 134, pp.127~131 (2001)
- Widmer HA, "Conditional protein phosphorylation regulates BK channel activity in rat cerebellar Purkinje neurons", J Physiol, 552, pp.379~391 (2003)
- Li W, "Characterization of voltage-and Ca2＋-activated K＋ channels in rat dorsal root ganglion neurons", J Cell Physiol, 212, pp.348~357 (2007)
- Yin XF, "Alterations in the expression of ATP-sensitive potassium channel subunit mRNA after acute peripheral nerve and spinal cord injury", Eur Neurol, 57, pp.4~10 (2007)