Increased presynaptic and postsynaptic α2-adrenoceptor activity in the spinal dorsal horn in painful diabetic neuropathy.
Diabetic neuropathy is a common cause of chronic pain that is not adequately relieved by conventional analgesics. The α(2)-adrenoceptors are involved in the regulation of glutamatergic input and nociceptive transmission in the spinal dorsal horn, but their functional changes in diabetic neuropathy are not clear. The purpose of the present study was to determine the plasticity of presynaptic and postsynaptic α(2)-adrenoceptors in the control of spinal glutamatergic synaptic transmission in painful diabetic neuropathy. Whole-cell voltage-clamp recordings of lamina II neurons were performed in spinal cord slices from streptozotocin-induced diabetic rats. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) evoked from the dorsal root and the frequency of spontaneous EPSCs (sEPSCs) were significantly higher in diabetic than vehicle-control rats. The specific α(2)-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK-14304) (0.1-2 μM) inhibited the frequency of sEPSCs more in diabetic than vehicle-treated rats. UK-14304 also inhibited the amplitude of evoked monosynaptic and polysynaptic EPSCs more in diabetic than control rats. Furthermore, the amplitude of postsynaptic G protein-coupled inwardly rectifying K(+) channel (GIRK) currents elicited by UK-14304 was significantly larger in the diabetic group than in the control group. In addition, intrathecal administration of UK-14304 increased the nociceptive threshold more in diabetic than vehicle-control rats. Our findings suggest that diabetic neuropathy increases the activity of presynaptic and postsynaptic α(2)-adrenoceptors to attenuate glutamatergic transmission in the spinal dorsal horn, which accounts for the potentiated antinociceptive effect of α(2)-adrenoceptor activation in diabetic neuropathic pain.
Department of Anesthesiology and Perioperative Medicine, Unit 110, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA. schen@mdanderson.org
Shao-Rui
SR
Chen
Hong
H
Chen
Wei-Xiu
WX
Yuan
Hui-Lin
HL
Pan
D000818:Animals; D003929:Diabetic Neuropathies / Q000150:complications / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D020671:Posterior Horn Cells / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis*; D015854:Up-Regulation / Q000502:physiology*
D018341:Receptors, Adrenergic, alpha-2
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):271-6
12496346
Br J Pharmacol. 1997 Dec;122(7):1478-82
9421298
Pain Med. 2002 Jun;3(2):85-91
15102154
Nature. 1989 Aug 24;340(6235):639-42
2570354
Anesthesiology. 2001 Aug;95(2):525-30
11506129
J Physiol. 1984 Apr;349:43-55
6145790
Brain Res. 2005 Mar 15;1038(1):76-82
15748875
Brain Res. 2006 Oct 18;1115(1):48-53
16920081
J Physiol. 2007 Mar 15;579(Pt 3):849-61
17218355
J Pharmacol Exp Ther. 2002 Jan;300(1):282-90
11752127
Brain Res Mol Brain Res. 1995 Dec 1;34(1):109-17
8750866
Neuroreport. 1999 Sep 9;10(13):2835-9
10511449
Eur J Pharmacol. 1987 Jun 19;138(2):169-77
3040431
Neurosci Lett. 2007 May 1;417(2):149-54
17412508
J Neurosci. 2010 Mar 24;30(12):4460-6
20335482
J Neurophysiol. 2002 Jun;87(6):2726-33
12037174
J Neurophysiol. 2006 May;95(5):3086-96
16467418
Neuroreport. 1998 Jan 26;9(2):243-7
9507963
Neuropharmacology. 2007 Jun;52(8):1624-30
17482651
Anesthesiology. 1999 Feb;90(2):509-14
9952159
J Pharmacol Exp Ther. 1995 Jan;272(1):207-14
7815335
J Neurosci. 1997 Sep 15;17(18):7157-65
9278550
Neuropharmacology. 2009 Aug;57(2):121-6
19422840
J Neurophysiol. 2002 Apr;87(4):1938-47
11929913
J Comp Neurol. 2009 Apr 1;513(4):385-98
19180644
Anesthesiology. 2000 Apr;92(4):968-76
10754615
Pain. 1994 May;57(2):153-160
8090511
Pain. 1998 May;76(1-2):151-7
9696468
J Neurochem. 2010 Jan;112(1):162-72
19840219
Anesthesiology. 2004 Jul;101(1):185-90
15220790
J Neurosci. 2006 Nov 22;26(47):12251-9
17122050
N Engl J Med. 1995 May 4;332(18):1210-7
7700316
Pain Med. 2008 Sep;9(6):660-74
18828198
J Neurosci. 1998 Aug 1;18(15):5928-37
9671679
Br J Anaesth. 1998 Aug;81(2):208-15
9813525
J Pharmacol Exp Ther. 2008 Nov;327(2):375-82
18669865
Mol Pharmacol. 1997 Jul;52(1):136-43
9224823
Pain. 2001 Feb 1;90(1-2):57-63
11166970
Neuroscience. 1999;93(4):1399-407
10501465
J Neurosci. 2009 Oct 21;29(42):13264-73
19846714
Eur J Pharmacol. 2008 Sep 11;592(1-3):62-6
18625215
Pharmacol Ther. 2008 Jan;117(1):141-61
17959251
Anesthesiology. 1993 Dec;79(6):1163-9; discussion 27A
8267190
J Neurosci Res. 1994 Oct 15;39(3):319-29
7869424
Pain. 1993 Apr;53(1):81-88
8316394