title: Mechanisms and management of diabetic painful distal symmetrical polyneuropathy.
abstract: Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment.
authors: Diabetes Research Unit, Sheffield Teaching Hospitals, Royal Hallamshire Hospital, Sheffield, UK.
authors: Solomon
authors: S
authors: Tesfaye
authors: Andrew J M
authors: AJ
authors: Boulton
authors: Anthony H
authors: AH
authors: Dickenson
mesh_terms: D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology; D000068736:Duloxetine Hydrochloride; D006801:Humans; D010146:Pain / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology; D000069583:Pregabalin; D013876:Thiophenes / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D013876:Thiophenes; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000068736:Duloxetine Hydrochloride
references: Postgrad Med J. 1983 Sep;59(695):556-9
references: 6634554
references: N Engl J Med. 2005 Mar 31;352(13):1324-34
references: 15800228
references: Clin J Pain. 2006 Oct;22(8):681-5
references: 16988563
references: Diabetes Care. 2006 Jul;29(7):1518-22
references: 16801572
references: Diabetologia. 1993 Feb;36(2):150-4
references: 8458529
references: Eur J Pain. 2009 Jul;13(6):582-7
references: 18782673
references: Annu Rev Biochem. 2007;76:387-417
references: 17579562
references: Pain. 2013 Dec;154(12):2616-2625
references: 23732189
references: Diabetes Care. 2006 Apr;29(4):883-7
references: 16567832
references: J Pain Symptom Manage. 2005 Apr;29(4):401-10
references: 15857744
references: J Pain Symptom Manage. 2005 Oct;30(4):374-85
references: 16256902
references: Br J Anaesth. 2008 Jul;101(1):8-16
references: 18417503
references: Eur J Neurol. 2010 Aug;17(8):1010-8
references: 20298428
references: Curr Opin Support Palliat Care. 2008 Jun;2(2):133-9
references: 18685411
references: J Med Genet. 2004 Mar;41(3):171-4
references: 14985375
references: Diabetes Care. 2011 Apr;34(4):818-22
references: 21355098
references: Pain. 2002 Sep;99(1-2):11-9
references: 12237180
references: Pain. 2010 Sep;150(3):439-450
references: 20627413
references: Diabetologia. 2003 Jul;46(7):934-9
references: 12819899
references: N Engl J Med. 2005 Jan 27;352(4):341-50
references: 15673800
references: Diabetes Care. 2004 Jun;27(6):1458-86
references: 15161806
references: Am J Med. 2009 Oct;122(10 Suppl):S22-32
references: 19801049
references: Pain. 2011 Dec;152(12):2701-2709
references: 21745713
references: Diabetes Metab. 2009 Jun;35(3):206-13
references: 19297223
references: Diabetes Metab Res Rev. 2011 Oct;27(7):629-38
references: 21695762
references: Curr Diabetes Rev. 2011 May;7(3):208-20
references: 21534920
references: Diabetologia. 2005 May;48(5):805-7
references: 15834549
references: Eur J Pharmacol. 2003 Jan 24;460(2-3):109-16
references: 12559370
references: Diabetes Care. 2002 Nov;25(11):2048-52
references: 12401755
references: Eur J Pain. 2002;6 Suppl A:51-60
references: 11888242
references: Acta Psychiatr Scand. 1983 Jun;67(6):361-70
references: 6880820
references: Diabetes Metab Res Rev. 2011 Oct;27(7):678-84
references: 21695760
references: Diabetes Care. 2003 Sep;26(9):2549-55
references: 12941717
references: Nature. 1997 Oct 23;389(6653):816-24
references: 9349813
references: Diabet Med. 2009 Oct;26(10):1019-26
references: 19900234
references: Pain. 1987 Aug;30(2):191-197
references: 3670870
references: Muscle Nerve. 2010 Aug;42(2):157-64
references: 20658599
references: Ther Adv Chronic Dis. 2011 Nov;2(6):371-6
references: 23251762
references: PLoS One. 2011 Mar 29;6(3):e17387
references: 21468319
references: Clin Ther. 2007;29 Suppl:2536-46
references: 18164920
references: J Neurosci. 2009 Apr 1;29(13):4076-88
references: 19339603
references: Diabetes Care. 2008 Jul;31(7):1448-54
references: 18356405
references: Neurotherapeutics. 2009 Oct;6(4):703-12
references: 19789074
references: Pain. 2006 Aug;123(3):231-243
references: 16697110
references: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5148-53
references: 20212137
references: J Neurosci. 2003 Aug 6;23(18):7227-36
references: 12904483
references: Diabetes Technol Ther. 2005 Jun;7(3):497-508
references: 15929681
references: J Neurol. 2011 Oct;258(10):1852-64
references: 21472496
references: Muscle Nerve. 1988 Jan;11(1):21-32
references: 3277049
references: Curr Med Res Opin. 2006 Oct;22(10):1911-20
references: 17022849
references: Diabet Med. 2004 Sep;21(9):976-82
references: 15317601
references: Diabetes Care. 1994 Nov;17(11):1281-9
references: 7821168
references: Neurology. 2011 May 17;76(20):1758-65
references: 21482920
references: Diabet Med. 2004 Feb;21(2):114-21
references: 14984445
references: Diabetes Care. 2010 Oct;33(10):2285-93
references: 20876709
references: Diabetes Care. 2011 Mar;34(3):718-20
references: 21282344
references: Diabet Med. 2002 Oct;19(10):870-3
references: 12358878
references: Pain Med. 2009 Mar;10(2):393-400
references: 19207236
references: Pain. 2011 Jan;152(1):131-139
references: 21187272
references: Diabetes Care. 2011 Oct;34(10):2220-4
references: 21852677
references: Nat Med. 2012 Jun;18(6):926-33
references: 22581285
references: Diabetes Care. 2010 Jul;33(7):1585-90
references: 20587724
references: Neuron. 2007 May 3;54(3):379-86
references: 17481392
references: Diabetes Care. 2010 Dec;33(12):2654-9
references: 20841612
references: Pain. 2004 Aug;110(3):697-706
references: 15288411
references: Clin J Pain. 2003 Sep-Oct;19(5):315-6
references: 12966257
references: Diabetes Care. 2005 Apr;28(4):956-62
references: 15793206
references: Lancet. 2009 Oct 10;374(9697):1252-61
references: 19796802
references: JAMA. 1998 Dec 2;280(21):1831-6
references: 9846777
references: Diabetes Technol Ther. 2001 Spring;3(1):29-50
references: 11469707
references: Nature. 2006 Dec 14;444(7121):894-8
references: 17167479
references: CNS Drugs. 2011 Dec 1;25(12):1023-34
references: 22133325
references: Diabetes Care. 2007 Mar;30(3):655-9
references: 17327336
references: BMC Neurol. 2009 Feb 10;9:6
references: 19208243
references: Eur J Neurol. 2010 Sep;17(9):1113-e88
references: 20402746
references: J Clin Endocrinol Metab. 2010 Nov;95(11):4802-11
references: 21051576
references: Diabet Med. 1994 Jan-Feb;11(1):17-21
references: 8181246
references: Pain. 2001 May;92(1-2):147-57
references: 11323136
references: Pain. 2004 Apr;108(3):248-257
references: 15030944