Neuropathic pain: mechanisms of development, principles of diagnostics and treatment

  • Dmytro Dmytriiev National Pirogov Memorial Medical University, Vinnytsia, Ukraine
  • Pylyp Prudius Vinnytsia Regional Clinical Highly Specialized Endocrinological Center
  • Olesia Zaletskaya National Pirogov Memorial Medical University, Vinnytsia, Ukraine
  • Yevhen Lisak National Pirogov Memorial Medical University, Vinnytsia, Ukraine
  • Yurii Rudnitsky Vinnytsia Regional Clinical Highly Specialized Endocrinological Center
  • Nadiia Korenchuk Vinnytsia Regional Clinical Highly Specialized Endocrinological Center
Keywords: pain, neuropathic pain, sensitization, diabetic peripheral neuropathy, analgesia

Abstract

Neuropathic pain is a pain caused by a disease or focal damage to the somatosensory nervous system. The prevalence of chronic pain with neuropathic features in different countries is estimated at 7–10 %. Damages to the nervous system can occur at the level of peripheral nerves, plexus and dorsal roots (peripheral neuropathic pain) or spinal cord and brain (central neuropathic pain). Neuropathic pain is based on pathological activation of pain pathways. Neuropathic pain occurs with diabetic polyneuropathy more often than with all polyneuropathies of another etiology. Hyperglycemia is the major cause of chronic diabetes mellitus and its progression. Since the cause of pain can rarely be cured, treatment is usually symptomatic. Neuropathic pain is generally poorly controlled by analgesics. NB management is started with conservative pharmacotherapy before applying invasive analgesia. Although there are many drugs that can be used in patients with DPN, monotherapy can not always stop pain syndrome. In addition, the patient may not tolerate the full therapeutic dose of the drug. All this dictates the need for combination therapy.

Downloads

Download data is not yet available.

References

Torrance N, Smith BH, Bennett MI, Lee AJ. The Epidemiology of Chronic Pain of Predominantly Neuropathic Origin. Results From a General Population Survey. The Journal of Pain [Internet]. Elsevier BV; 2006 Apr;7(4):281–9. Available from: https://doi.org/10.1016/j.jpain.2005.11.008

Bouhassira D, Attal N. Diagnosis and assessment of neuropathic pain: The saga of clinical tools. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2011 Mar;152(Supplement):S74–S83. Available from: https://doi.org/10.1016/j.pain.2010.11.027

Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2008 Jun;136(3):380–7. Available from: https://doi.org/10.1016/j.pain.2007.08.013

International Working Group on the Diabetic Foot. Available from: https://iwgdfguidelines.org

Freynhagen R, Baron R, Tölle T, Stemmler E, Gockel U, Stevens M, et al. Screening of neuropathic pain components in patients with chronic back pain associated with nerve root compression: a prospective observational pilot study (MIPORT). Current Medical Research and Opinion [Internet]. Informa Healthcare; 2006 Feb;22(3):529–37. Available from: https://doi.org/10.1185/030079906x89874

Abbott CA, Malik RA, van Ross ERE, Kulkarni J, Boulton AJM. Prevalence and Characteristics of Painful Diabetic Neuropathy in a Large Community-Based Diabetic Population in the U.K. Diabetes Care [Internet]. American Diabetes Association; 2011 Aug 18;34(10):2220–4. Available from: https://doi.org/10.2337/dc11-1108

Lee AYW, Chung SSM. Contributions of polyol pathway to oxidative stress in diabetic cataract. The FASEB Journal [Internet]. FASEB; 1999 Jan;13(1):23–30. Available from: https://doi.org/10.1096/fasebj.13.1.23

Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, et al. Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. Journal of Clinical Investigation [Internet]. American Society for Clinical Investigation; 1998 Mar 1;101(5):1142–7. Available from: https://doi.org/10.1172/jci119885

Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes [Internet]. American Diabetes Association; 1998 Jun 1;47(6):859–66. Available from: https://doi.org/10.2337/diabetes.47.6.859

Derubertis FR, Craven PA. Activation of protein kinase C in glomerular cells in diabetes. Mechanisms and potential links to the pathogenesis of diabetic glomerulopathy. Diabetes [Internet]. American Diabetes Association; 1994 Jan 1;43(1):1–8. Available from: https://doi.org/10.2337/diabetes.43.1.1

Xia P, Inoguchi T, Kern TS, Engerman RL, Oates PJ, King GL. Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes [Internet]. American Diabetes Association; 1994 Sep 1;43(9):1122–9. Available from: https://doi.org/10.2337/diabetes.43.9.1122

Koya D, Jirousek MR, Lin YW, Ishii H, Kuboki K, King GL. Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. Journal of Clinical Investigation [Internet]. American Society for Clinical Investigation; 1997 Jul 1;100(1):115–26. Available from: https://doi.org/10.1172/jci119503

Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, et al. Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC beta Inhibitor. Science [Internet]. American Association for the Advancement of Science (AAAS); 1996 May 3;272(5262):728–31. Available from: https://doi.org/10.1126/science.272.5262.728

Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, et al. Regulation of Endothelial Constitutive Nitric Oxide Synthase Gene Expression in Endothelial Cells and In Vivo. Circulation [Internet]. Ovid Technologies (Wolters Kluwer Health); 2000 Feb 15;101(6):676–81. Available from: https://doi.org/10.1161/01.cir.101.6.676

Studer RK, Craven PA, DeRubertis FR. Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes [Internet]. American Diabetes Association; 1993 Jan 1;42(1):118–26. Available from: https://doi.org/10.2337/diabetes.42.1.118

Feener EP, Xia P, Inoguchi T, Shiba T, Kunisaki M, King GL. Role of Protein Kinase C in Glucose- and Angiotensin II-Induced Plasminogen Activator Inhibitor Expression1. Progression of Chronic Renal Diseases [Internet]. S. Karger AG; 180–7. Available from: https://doi.org/10.1159/000425092

Kolm-Litty V, Sauer U, Nerlich A, Lehmann R, Schleicher ED. High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. Journal of Clinical Investigation [Internet]. American Society for Clinical Investigation; 1998 Jan 1;101(1):160–9. Available from: https://doi.org/10.1172/jci119875

Sayeski PP, Kudlow JE. Glucose Metabolism to Glucosamine Is Necessary for Glucose Stimulation of Transforming Growth Factor-α Gene Transcription. Journal of Biological Chemistry [Internet]. American Society for Biochemistry & Molecular Biology (ASBMB); 1996 Jun 21;271(25):15237–43. Available from: https://doi.org/10.1074/jbc.271.25.15237

Wells L, Hart GW. O-GlcNAc turns twenty: functional implications for post-translational modification of nuclear and cytosolic proteins with a sugar. FEBS Letters [Internet]. Wiley; 2003 Jun 11;546(1):154–8. Available from: https://doi.org/10.1016/s0014-5793(03)00641-0

Du X-L, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, et al. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proceedings of the National Academy of Sciences [Internet]. Proceedings of the National Academy of Sciences; 2000 Oct 24;97(22):12222–6. Available from: https://doi.org/10.1073/pnas.97.22.12222

Korshunov SS, Skulachev VP, Starkov AA. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Letters [Internet]. Wiley; 1997 Oct 13;416(1):15–8. Available from: https://doi.org/10.1016/s0014-5793(97)01159-9

Murashko NK. Neuropathic pain: an interdisciplinary approach in diagnosis and treatment. EFNS Recommendations. Art of treatment. Magazine of the modern doctor; 2013; 6:47-9.

Keen H, Fukker J, Menzinger G. Early closure of European Pimagedine trial. The Lancet [Internet]. Elsevier BV; 1997 Jul;350(9072):214–5. Available from: https://doi.org/10.1016/s0140-6736(97)26029-0

Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia [Internet]. Springer Science and Business Media LLC; 2001 Feb 5;44(2):129–46. Available from: https://doi.org/10.1007/s001250051591

Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. European Journal of Neurology [Internet]. Wiley; 2006 Nov;13(11):1153–69. Available from: https://doi.org/10.1111/j.1468-1331.2006.01511.x

Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European Journal of Neurology [Internet]. Wiley; 2010 Apr 7;17(9):1113–e88. Available from: https://doi.org/10.1111/j.1468-1331.2010.02999.x

Finnerup NB, Attal N. Pharmacotherapy of neuropathic pain: time to rewrite the rulebook? Pain Management [Internet]. Future Medicine Ltd; 2016 Jan;6(1):1–3. Available from: https://doi.org/10.2217/pmt.15.53

Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, et al. Upregulation of Dorsal Root Ganglion α2δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats. The Journal of Neuroscience [Internet]. Society for Neuroscience; 2001 Mar 15;21(6):1868–75. Available from: https://doi.org/10.1523/jneurosci.21-06-01868.2001

Starostina OG. State budgetary institution of health care of the Moscow region "MONIKI them. M. F. Volodymyrsky ". RMJ. 2017; 22:1665-76.

Tesfaye S, Wilhelm S, Lledo A, Schacht A, Tölle T, Bouhassira D, et al. Duloxetine and pregabalin: High-dose monotherapy or their combination? The “COMBO-DN study” – a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain. Pain [Internet]. Ovid Technologies (Wolters Kluwer Health); 2013 Dec;154(12):2616–25. Available from: https://doi.org/10.1016/j.pain.2013.05.043

Mohort TV. Neuropathy in diabetes mellitus: modern treatment principles. Medical News. 2008; 1:40-7.

Strokov IA. HBOU VPO «First MDMU them. І.М. Sechenov» Ministry of Health of Russia. RMJ. 2008; 28:1892.

Wiffen PJ, Derry S, Bell RF, Rice AS, Tölle TR, Phillips T, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews [Internet]. Wiley; 2017 Jun 9; Available from: https://doi.org/10.1002/14651858.cd007938.pub4

Balabolkin MI. Diabetic neuropathy: pathogenesis, diagnosis, classification, prognostic value, treatment: educational method. Manual. Moscow. Examination. 2003.

Galstyan GR, Udovichenko OV, Tokmakova AY, Antsiferov MB. Diabeticheskaya neyropatiya: epidemiologicheskie i klinicheskie aspekty. Diabetes mellitus [Internet]. Endocrinology Research Centre; 2000 Mar 15; (1):19. Available from: https://doi.org/10.14341/2072-0351-5738

Gurieva IW. Diabetic peripheral sensorimotor neuropathy: method. Recommendation; 2000:1-76.

Dedov II. Diabetic foot. Practical Medicine; 2005:48-57.

Kotov SV. Diabetic neuropathy. Medicine; 2000:45-150.

Wein AM. Pain syndromes in neurological practice. Medicine; 2001:249- 67.

Yakhno NN. Methodical recommendations for the diagnosis and treatment of neuropathic pain. Under the editorship of the Academy of Sciences of the Russian Academy of Sciences. Russian Academy of Medical Sciences publication: 2008:32.

Galstyan GR. Diabetic neuropathy. In the book: Complications of diabetes mellitus: treatment, prevention. Medical Information Agency; 2017:608-28.

The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. Diabetes [Internet]. American Diabetes Association; 1996 Oct 1;45(10):1289–98. Available from: https://doi.org/10.2337/diabetes.45.10.1289

Davydov OS. The peripheral and central mechanisms of transition of acute to chronic pain and the possible role of cyclooxygenase-2 inhibition in the prevention of pain syndrome chronization. Neurology, Neuropsychiatry, Psychosomatics [Internet]. IMA Press, LLC; 2016 Jan 1;8(2):10–6. Available from: https://doi.org/10.14412/2074-2711-2016-2-10-16

Jann MW, Slade JH. Antidepressant Agents for the Treatment of Chronic Pain and Depression. Pharmacotherapy [Internet]. Wiley; 2007 Nov;27(11):1571–87. Available from: https://doi.org/10.1592/phco.27.11.1571

Stacey BR, Dworkin RH, Murphy K, Sharma U, Emir B, Griesing T. Pregabalin in the Treatment of Refractory Neuropathic Pain: Results of a 15-Month Open-Label Trial. Pain Medicine [Internet]. Oxford University Press (OUP); 2008 Nov;9(8):1202–8. Available from: https://doi.org/10.1111/j.1526-4637.2008.00423.x

Kempler P. Neuropathies. Pathomechanism, clinical presentation, diagnosis, therapy. Springer Scientific Journal. 2002;10(8):142-9.

Tesfaye S, Selvarajah D, Gandhi R, Greig M, Shillo P, Fang F, et al. Diabetic peripheral neuropathy may not be as its name suggests. PAIN [Internet]. Ovid Technologies (Wolters Kluwer Health); 2016 Feb;157:S72–S80. Available from: https://doi.org/10.1097/j.pain.0000000000000465

Sorensen L, Siddall PJ, Trenell MI, Yue DK. Differences in Metabolites in Pain-Processing Brain Regions in Patients With Diabetes and Painful Neuropathy. Diabetes Care [Internet]. American Diabetes Association; 2008 Feb 25;31(5):980–1. Available from: https://doi.org/10.2337/dc07-2088

Thomas PK, Gries FA, Low PA, Ziegler D.Classification of the diabetic neuropathies. Textbook of Diabetic Neuropathy. Stuttgart Thieme; 2003:175–7.

Backonja M. Anticonvulsants for the treatment of neuropathic pain syndromes. Current Pain and Headache Reports [Internet]. Springer Science and Business Media LLC; 2003 Feb;7(1):39–42. Available from: https://doi.org/10.1007/s11916-003-0008-2

Naumenko WG. Pathogenetic therapy of diabetes complications. International Endocrinological Journal; 2006;1(3):55.

Нейропатичний біль: механізми розвитку, принципи діагностики та лікування
Published
2019-07-15
How to Cite
1.
Dmytriiev D, Prudius P, Zaletskaya O, Lisak Y, Rudnitsky Y, Korenchuk N. Neuropathic pain: mechanisms of development, principles of diagnostics and treatment. PMJUA [Internet]. 2019Jul.15 [cited 2019Nov.20];4(2):4-32. Available from: https://painmedicine.org.ua/index.php/pnmdcn/article/view/195
Section
Problem article