Author(s): Munish Kakar, Pakhi Chakarborty, Tapan Behl, Sukhbir Singh, Neelam Sharma, Monika Sachdeva


DOI: 10.5958/0974-360X.2020.00956.7   

Address: Munish Kakar1, Pakhi Chakarborty1, Tapan Behl1*, Sukhbir Singh1, Neelam Sharma1, Monika Sachdeva2
1Chitkara College of Pharmacy, Chitkara University, Punjab, India.
2Fatima College of Health Sciences, Alain, UAE.
*Corresponding Author

Published In:   Volume - 13,      Issue - 11,     Year - 2020

Diabetes is major fatal disease that gives the outbreak to the vast mortality rate in India. Most of the diabetic patients affected by foot ulcers and deposition of lesions in foot, arms, hands, and legs due to inflammation caused by means of various physical and chemical extremities contributing in the etiology of inflammatory diabetic neuropathy. In various neuropathic pains the most common is diabetic peripheral neuropathy (DPN) which affect leg region. It is characterized by the small and large nerve fibers autonomic alterations. The symptoms of DPN is basically occurs above the 50 years of age group. Inflammation, oxidative stress and mitochondrial dysfunction are the three main alterations involved in diabetic neuropathy. Inflammation persuades the stimulation of activator protein-1, nuclear factor kappa b (NF-Kb), and protein kinases stimulated by mitogen. Prolonged neuropathic damage in peripheral region will not be recovered, but there are many recent researches came out by which the progression of the lesion can be controlled by some effective measures. Many effective non-steroidal anti-inflammatory drugs have the potent actions on the peripheral pain in inflammatory diabetic neuropathy as well as multifocal sites in the polyneuropathy. Due to many complications occur in diabetes mellitus certain sites are prone to spread the inflammatory lesions, resulting in many difficult problems which can be treated as per the progression of the disease. Many patients were treated by the certain combinations of medication like prednisone and other non-steroidal anti-inflammatory diseases (NSAIDs), or can be diagnosed by the plasmapheresis and intravenous immune globulins.

Cite this article:
Munish Kakar, Pakhi Chakarborty, Tapan Behl, Sukhbir Singh, Neelam Sharma, Monika Sachdeva. Insight into the role of Inflammation in progression of Diabetes associated Neuropathy. Research J. Pharm. and Tech. 2020; 13(11):5477-5483. doi: 10.5958/0974-360X.2020.00956.7

Munish Kakar, Pakhi Chakarborty, Tapan Behl, Sukhbir Singh, Neelam Sharma, Monika Sachdeva. Insight into the role of Inflammation in progression of Diabetes associated Neuropathy. Research J. Pharm. and Tech. 2020; 13(11):5477-5483. doi: 10.5958/0974-360X.2020.00956.7   Available on:

1.    Toth C, Brussee V, Cheng C, Zochodne DW. Sensory neuron. J Neuropathol Exp Neurol. 2004; 63: 561-573.
2.    Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappa B. Diabetes. 2001; 50: 2792-2808.
3.    Bierhaus A, Haslbeck KM, Humpert PM, Liliensiek B, Dehmer T et al. Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily. J Clin Invest. 2004; 114: 1741-1751.
4.    Schiekofer S, Andrassy M, Chen J, Rudofsky G, Schneider J, et al. Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappa B in PBMCs. Diabetes. 2003; 52: 621-633.
5.    Devaraj S, Dasu MR, Rockwood J, Winter W, Griffen SC et al. Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state. J Clin Endocrinol Metab. 2008; 93: 578-583.
6.    Toth C, Rong LL, Yang C, Martinez J, Song F et al. Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy. Diabetes. 2008; 57: 1002-1017.
7.    Dasu MR, Devaraj S, Zhao L, Hwang DH, Jialal I. High glucose induces toll-like receptor expression in human monocytes: mechanism of activation of Diabetes. Diabetes. 2008; 57: 3090-3098.
8.    Devaraj S, Dasu MR, Park SH, Jialal I. Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes. Diabetologia. 2009; 52: 1665-1668.
9.    Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000; 25: 187-191.
10.    Rudofsky G, Reismann P, Witte S, Humpert PM, Isermann B et al. Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 Diabetes. Diabetes Care. 2004; 27: 179-183.
11.    Uceyler N, Kafke W, Riediger N, He L, Necula G et al. Elevated proinflammatory cytokine expression in affected skin in small fiber neuropathy. Neurology. 2010; 74: 1806-1813.
12.    Yamakawa I, Kojima H, Terashima T, Katagi M, Oi J et al. Inactivation of TNF{alpha} Ameliorates Diabetic Neuropathy in Mice. Am J Physiol Endocrinol Metab. 2011; 301: 844-852.
13.    Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, et al. Chemokines and Glycoprotein120 Produce Pain Hypersensitivity by Directly Exciting Primary Nociceptive Neurons. J Neurosci 2001; 21: 5027-5035.
14.    White FA, Wilson NM. Chemokines as pain mediators and modulators. Curr Opin Anaesthesiol. 2008; 21: 580-585.
15.    Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 2003; 100: 7265-7270. H.C. Powell, A.P. Mizisin, in Encyclopedia of Neuroscience, 2009.
16.    Pop-Busui R, Ang L, Holmes C, Gallagher K, Feldman EL. Inflammation as a Therapeutic Target for Diabetic Neuropathies. Current Diabetes Reports. 2016; 16(3).
17.    Ziegler D, Keller J, Maier C, Pannek J. Diabetic neuropathy. Exp. Clin. Endocrinol. Diabet. Off. J. Ger. Soc. Endocrinol. Ger. Diabet. Assoc. 2014; 122: 406–415.
18.    Said G. Diabetic neuropathy. Handbook Clin. Neurol. 2013; 115: 579–589.
19.    Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and oxidative stress in diabetic neuropathy: Futuristic strategies based on these targets. Int. J. Endocrinol. 2014; 674987
20.    Boulton AJM, Augur E, Ayyer DR et al. Diabetic thoracic polyradiculopathy presenting as an abdominal swelling. BMJ. 1984; 289: 798-799.
21.    Greene DA, Sima AAF, Stevens MJ et al. Complications: Neuropathy, pathogenetic consideration. Diabetes Care. 1992; 15: 1902-25.
22.    Feldman EL, Stevens MJ, Greene DA. Pathogenesis of diabetic neuropathy. Clin Neuro Sci. 1997; 4: 365-370.
23.    Sharma AK, Thom. Vlassara H, Brownlee M, Cerami A. Excessive non enzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats. Diabetes 1983; 32: 670-674.
24.    Ryle C, Donaghy M. Glycation of peripheral nerve proteins in diabetes mellitus. J Neurol Sci 1995; 129: 62-8.
25.    Vlassara H. Receptor mediated interactions of advanced glycosylated end products with cellular components within diabetic tissues. Diabetes. 1992; 41: 52-56.
26.    Gingliano D, Ceriello A, Pawlisso G. Oxidalive stress and diabetic vascular complications. Diabetes Care 1996; 19: 257-267.
27.    Jamal GA, Carmichael H. The effect of gamma linolenic acid on human diabetic peripheral neuropathy: a doubled blind placebocontrolled trial. Diabet Med. 1990; 7: 319-323.
28.    Britland ST, Yound RJ, Sharma AK, Clarke BF. Relationship of undo neural capillary abnormalities to type and severity of diabetic polyneuropathy. Diabetes. 1990; 39; 909- 913.
29.    Faradji V, Sotelo J. Low serum levels of nerve growth factor in diabetic neuropathy. Acta Neurol Scand. 1990; 81: 402-413
30.    Dyck PJ, Kratz KM, Karnes JL et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the rochester diabetic neuropathy study. Neurology. 1993; 43:817.
31.    Dyck PJ, Litchy WJ, Lehman KA et al. Variables influencing neuropathic endpoints: the Rochester Diabetic Neuropathy Study of Healthy Subjects. Neurology. 1995; 45:1115.
32.    Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008; 120:1.
33.    Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (author's transl). Diabete Metab. 1977; 3:97.
34.    Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (2nd part) (author's transl). Diabete Metab. 1977; 3:173.
35.    Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (3rd and last part) (author's transl). Diabete Metab. 1977; 3:245.
36.    Abbott CA, Malik RA, van Ross ER et al. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care. 2011; 34:2220.
37.    Young MJ, Boulton AJ, MacLeod AF et al. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993; 36:150.
38.    Sands ML, Shetterly SM, Franklin GM, Hamman RF. Incidence of distal symmetric (sensory) neuropathy in NIDDM. The San Luis Valley Diabetes Study. Diabetes Care. 1997; 20:322.
39.    Forrest KY, Maser RE, Pambianco G et al. Hypertension as a risk factor for diabetic neuropathy: a prospective study. Diabetes. 1997; 46:665.
40.    Jaiswal M, Lauer A, Martin CL et al. Peripheral neuropathy in adolescents and young adults with type 1 and type 2 diabetes from the SEARCH for Diabetes in Youth follow-up cohort: a pilot study. Diabetes Care. 2013; 36:3903.
41.    Jin HY, Park TS. Role of inflammatory biomarkers in diabetic peripheral neuropathy. Journal of Diabetes Investigation. 2018.
42.    Dyck PJ, Davies JL, Wilson DM, Service FJ, L. J. Melton LJ, O’Brien PC. Risk factors for severity of diabetic polyneuropathy: intensive longitudinal assessment of the Rochester Diabetic Neuropathy Study Cohort. Diabetes Care. 1999; 22(9): 1479–1486.
43.    Lee WJ, Jang S, Lee SH, Lee H. Correlation between the severity of diabetic peripheral polyneuropathy and glycosylated hemoglobin levels: a quantitative study,” Annals of Rehabilitation Medicine. 2016; 40 (2): 263–270.
44.    Ybarra-Mu˜noz J, Jurado-Campos J, Garcia-Gil M et al. Cardiovascular disease predicts diabetic peripheral polyneuropathy in subjects with type 2 diabetes: A 10-year Prospective Study. European Journal of Cardiovascular Nursing. 2016; 15(4): 248–254.
45.    Dyck PJ, Lais A, Karnes JL et al. Fiber loss is a primary and multifocal in sural nerves in diabetic polyneuropathy. Annals of Neurology. 1973; 10: 13–18.
46.    Dyck PJ, Giannini C. Pathologic alterations in the diabetic neuropathies of humans: a review. Journal of Neuropathology and Experimental Neurology. 1973; 55(12): 1181.
47.    Mendell JR, Barohn RJ, Freimer ML et al. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 2001; 56:445–449.
48.    Cats EA, van der Pol WL, Piepers S et al. Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy. Neurology. 2010; 75: 818–825.
49.    Koski CL. Therapy of CIDP and related immunemediated neuropathies. Neurology. 2002; 59: S22–S27.
50.    Eftimov F, Vermeulen M, van Doorn PA, Brusse E, van Schaik IN; on behalf of the PREDICT study group. Longterm remission of CIDP after pulsed dexamethasone or short-term prednisolone treatment. Neurology. 2012; 78: 1079–1084.
51.    Pop-Busui R et al. Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction. J Am Coll Cardiol. 2004; 44(12):2368–2374.
52.    Wang Y. Enhanced inflammatory response via activation of NF-kappaB in acute experimental diabetic neuropathy subjected to ischemia-reperfusion injury. J Neurol Sci. 2006; 247(1):47–52.
53.    Cameron NE, Cotter MA. Pro-inflammatory mechanisms in diabetic neuropathy: focus on the nuclear factor kappa B pathway. Curr Drug Targets. 2008; 9(1):60–67.
54.    Kellogg AP et al. Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fibers loss in experimental diabetes. Diabetes. 2007; 56(12):2997–3005.
55.    Mezher MN, Jawad DHA. Evaluation of tumor necrosis factor- alpha in hepatitis c virus with diabetes mellitus and non diabetes mellitus patients. Research Journal of Pharmacy and Technology. 2017; 10(10):3260-3263.
56.    Cheng HT. p38 mediates mechanical allodynia in a mouse model of type 2 diabetes. Mol Pain. 2010; 6:28.
57.    Pavithra RS, Varghese S. Gingival tissue level of interleukin-1 in diabetic patient with chronic periodontitis. Research Journal of Pharmacy and Technology. 2017;10(12): 4442-4444
58.    Elaiyaraja V, Hema Latha M, Subathra Devi. C. Optimization and Production of Anti-Inflammatory and Anti-Diabetic Metabolites from Marine Streptomyces sp. VITJS8. Research Journal of Pharmacy and Technology. 2018; 11(7):2868-2886.
59.    Anitha KN, Geetha KM. Soluble Epoxide Hydrolase: A Pharmaceutical Target for Inflammation. Research Journal of Pharmacy and Technology. 2019; 10(12):513-5118.
60.    Chowdary RP, Praveen. D, Vijey Aanandhi. M. A Prospective Study on Incidence of Dyslipidemia in Diabetes Mellitus. Research Journal of Pharmacy and Technology. 2017; 10(2):431-433.
61.    Samidha K, Vrushali K. Management of Diabetes: A Review. Research Journal of Pharmacy and Technology. 2014; 7(9): 1065-1072

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