Effect of Endurance Training on Peripheral Neuropathic Pain and Inflammatory Mediators in Diabetic Rats

Document Type : Original Article

Authors

• Siros Hosseini Askarabadi
• Rahim Mirnasori
• Masoud Rahmati

Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran

Abstract

Introduction: The pain caused by peripheral nervous neuropathy is one of the most important factors affecting the quality of life of people with diabetes mellitus. In this vein, considering the possible anti-inflammatory effect of regular exercise on reducing pain associated with diabetes, the present study intends to evaluate the effect of six weeks of endurance training on peripheral neuropathic pain, interleukin- 6 (IL-6) and C- reactive protein (CRP) in diabetic neuropathic rats. Methods: 40 male Wistar rats (age: 8 weeks old; weight 200-250g) were randomly divided into 4 equal groups of 10, including: diabetic neuropathy training (DNT), diabetic neuropathy control (DNC), healthy training (HT) and healthy control (HC). The diabetic groups were induced by intraperitoneal injection of streptozotocin (STZ) and two weeks after induction of diabetes, behavioral pain tests were administered and after verifying the neuropathic pain, the endurance training protocol was performed for 6 weeks and 5 sessions per week. For analysis of data paired sample t- test, ANOVA and Bonferroni’s post hoc test were used (p≤0.05). Results: In different groups before and after the training program, the mean reduction in glucose in the training groups was significantly higher than the control groups (P≤0.05); Serum levels of IL-6 and CPR in the diabetic groups was significantly higher than the training groups (P≤0.05); The mean pain of the diabetic neuropathy group were significantly higher than the control rats (P≤0.05); Also, the correlation between IL6, CRP and glucose with the threshold of pain was significantly positive (P≤0.05). Conclusion: It seems that endurance exercise in diabetic neuropathic rats can affect the reduction of pain and inflammatory factors, and aerobic training is a suitable method for preventing, controlling and treating pain caused by diabetes.

Keywords

• Training
• Peripheral Neuropathic Pain
• Diabetes
• IL-6
• CRP

---

References

1-      Yoon H, Thakur V, Isham D, Fayad M, Chattopadhyay M. Moderate exercise training attenuates inflammatory mediators in DRG of Type 1 diabetic rats. Exper Neuro. 2015; 267:107- 114.

2-      Salehi OR, Hoseini A. The effects of endurance trainings on serum BDNF and insulin levels in streptozotocin- induced diabetic rats. SH Kh J. 2017; 5 (2): 52- 61.

3-      Shih A, Miletic V, Miletic G, Smith LJ. Midazolam administration reverses thermal hyperalgesia and prevents GABA transporter loss in a rodent model of neuropathic pain. Anesthesia Anal J. 2008; 106 (4): 1296.

4-      Banitalebi E, Razavi T, Norian M, Bagheri L. The effect of combined aerobic exercise training and green tea extract on serum TNF- α and IL- 6 levels in obese women with type 2 diabetes. Daneshvar Med J. 2016; 23 (123): 11- 20.

5-      Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity. Diabetologia. 2016; 59: 879- 894.

6-      Safarzade AR, Gharakhanlou R, Hedayati M, Talebi-Garakani E. The effect of 4 weeks resistance training on serum vaspin, IL- 6, CRP and TNF- α concentrations in diabetic rats. Endocrinol Metab Iranian J. 2012; 14 (1): 68- 74.

7-      Nemati J, Ghodrat L, Hojjati F. Inflammatory effect of severe periodic exercises in overweight women and type 2 diabetes. J Physiol Exe Phys Act. 2017; 10: 79- 88.

8-      Xie K, Qiao F, Sun Y, Wang G, Hou L. Notch signaling activation is critical to the development of neuropathic pain. BMC anesthesiology. 2015; 15 (1): 41.

9-       Ghodsbin S, Farsi S, Hosseini S A. Correlation between CRP and IL-6 serum levels after induction of diabetes and eight weeks resistance training in rats. Rep Health Care J. 2017; 4 (4): 1- 9.

10-  Molanouri-Shamsi M, Fallah M, Mahdavi M. The effect of resistance training on skeletal muscle levels of inflammatory factors in diabetic rats. Feyz J. 2014; 18 (5): 477- 483.

11-  Dabbagh Nikookheslat S, Sari Sarraf V, Salek Zamani Y, Abdollahpour Alni M, Fathollahi S. Effect of 12 weeks resistance training on neural conduction in type 2 diabetes men with peripheral neuropathy. Urumia Med Sci J. 2016; 28 (5): 353- 362.

12-  Yan JE, Yuan W, Lou X, Zhu T. Streptozotocin-induced diabetic hyperalgesia in rats is associated with upregulation of Toll-like receptor 4 expression. Neuro Let J. 2012; 526 (1): 54- 58.

13-  Wei M, Ong L, Smith MT, Ross FB, Schmid K, Hoey AJ, Burstow D, Brown L. The streptozotocin‐diabetic rat as a model of the chronic complications of human diabetes. Heart Lung J. 2003; 12 (1): 44- 50.

14-  Chae CH, Jung SL, An SH, Jung CK, Nam SN, Kim HT. Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. PHysiol Biol J. 2011; 67 (2): 235- 241.

15-  Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain J. 1977; 4: 161- 174.

16-  Vincent AM, Callaghan BC, Smith AL, Feldman EL. Diabetic neuropathy: cellular mechanisms as therapeutic targets. Nature Rev Neuro J. 2011; 7 (10): 573.

17-  Mardanpour Shahrekordi Z, Banitalebi E, Faramarzi M. The effect of resistance training on levels of interlukine- 6 and high- sensitivity C - reactive protein in older- aged women. Elderly Health J. 2017; 3 (1): 35- 41.

18-  Kajitani N, Shikata K, Nakamura A, Nakatou T, Hiramatsu M, Makino H. Microinflammation is a common risk factor for progression of nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Clin Pract J. 2010; 88 (2): 171- 176.

19-  Salama ME, El-Damarawi MA. Effect of two exercise varieties on fetuin- A plasma level in experimental diabetic nephropathy. Tanta Med J. 2017; 45 (1): 21- 28.

20-  Libardi CA, De GS, Cavaglieri CR, Madruga VA, Chacon-Mikahil MP. Effect of resistance, endurance, and concurrent training on TNF-α, IL-6, and CRP. Med Sci Sport Exer. 2012; 44 (1): 50- 56.

21-  Nicklas BJ, Hsu FC, Brinkley TJ, Church T, Goodpaster BH, Kritchevsky SB, Pahor M. Exercise training and plasma C‐reactive protein and interleukin‐6 in elderly people. J Am Geriatrics Society. 2008; 56 (11): 2045- 2052.

22-  Prestes J, Shiguemoto G, Botero JP, Frollini A, Dias R, Leite R, et al. Effects of resistance training on resistin, leptin, cytokines, and muscle force in elderly post-menopausal women. Sports Sci J. 2009; 27 (14): 1607- 1615.

23-  Meyer T, Gabriel HH, RÄtz M, MÜller HJ, Kindermann W. Anaerobic exercise induces moderate acute phase response. Med Sci Sport Exer J. 2001; 33 (4): 549- 555.

24-  Cunniffe B, Hore AJ, Whitcombe DM, Jones KP, Baker JS, Davies B. Time course of changes in immuneoendocrine markers following an international rugby game. Eur Appl Physiol J. 2010; 108 (1): 113.

25-  Touvra AM, Volaklis KA, Spassis AT, Zois CE, Douda HT, Kotsa K, et al. Combined strength and aerobic training increases transforming growth factor-β1 in patients with type 2 diabetes. Hormones J. 2011; 10 (2): 125- 130.

26-  Yu Z, Ye X, Wang J, Qi Q, Franco OH, Rennie KL, et al. Associations of physical activity with inflammatory factors, adipocytokines, and metabolic syndrome in middle-aged and older chinese people. Circulation J. 2009; 119 (23): 2969- 2977.

27-  Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. Am Cardiol J. 2005; 45 (10): 1563- 1569.

28-  Yousefipoor P, Tadibi V, Behpoor N, Parnow A, Delbari E, Rashidi S. The effect of 8- week aerobic and concurrent (aerobic- resistance) exercise training on serum IL- 6 levels and insulin resistance in type 2 diabetic patients. J Shahid Sadoughi Univ Med Sci. 2013; 21 (5): 619- 663.

29-  Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, et al. Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr Metab Cardiol Dis J. 2010; 20 (8): 608- 617.

30-  Calcutt NA. Potential mechanisms of neuropathic pain in diabetes. Int Rev Neuro J. 2002; 50: 205- 228.

31-  Ridker PM. From C- reactive protein to interleukin- 6 to interleukin- 1. Circ Res. 2016; 118: 145- 156.

32-  Hosseini SA, Nikbakht H, Azarbayjani MA. The effect of aqua extract of saffron with resistance training on glycemic indexes of streptozotocin induced diabetic rats. Armaghane Danesh J. 2013; 18 (4): 284- 294.

33-  Annibalini G, Lucertini F, Agostini D, Vallorani L, Gioacchini A, Barbieri E, et al. Concurrent aerobic and resistance training has anti- inflammatory effects and increases both plasma and leukocyte levels of IGF-1 in late middle-aged type 2 diabetic patients. Oxi Med Cell Long J. 2017; 1: 1- 10.

34-  Vissers KC, Geenen F, Biermans R, Meert TF. Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury. Pharm Biochem. 2006; 84 (3): 479- 486.

35-  Romero-Zurita A, Carbonell-Baeza A, Aparicio VA, Ruiz JR, Tercedor P, Delgado-Fernández M. Effectiveness of a tai-chi training and detraining on functional capacity, symptomatology and psychological outcomes in women with fibromyalgia. Eviden Compl Alter Medic J. 2012; 2012: 614196.

36-  Yoo M, Sharma N, Pasnoor M, Kluding PM. Painful diabetic peripheral neuropathy: presentations, mechanisms, and exercise therapy. Diab Meta J. 2013: 10: 5.