Antinociceptive Effect of Curcumin, an Effective Constituent of Turmeric, in Diabetic Rats and Evaluation of the Involvement of Lipid Peroxidation

Authors
M. Roghani 1
T. Baluchnejadmojarad 2
1 1- Neurophysiology Research Center, Shahed University, Tehran, Iran 2- Department of Physiology, Faculty of Medicine, Shahed University, Tehran, Iran
2 Professor, Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Objective: This study was designed to investigate the antinociceptive effect of curcumin in diabetic rats by using the formalin and hot tail immersion tests.
Methods: Wistar rats were divided into the following six groups: control; curcumin-treated control (50 mg/kg); diabetic; sodium salicylate (SS)-treated diabetic; and two curcumin-treated diabetic groups (10 and 50 mg/kg). Curcumin was administered seven days after streptozotocin injection for a total of five weeks.
Results: High-dose curcumin treatment of diabetic rats reduced the pain score in both acute and chronic phases of the formalin test (p<0.05). SS-treated diabetic rats had a reduction in pain score only in the chronic phase of the formalin test (p<0.05). In the hot tail immersion test, diabetic rats showed a significant reduction in tail flick latency compared to the control group (p<0.01). High-dose curcumin treated diabetic rats showed significantly increased latency relative to untreated diabetic rats (p<0.05). Diabetic rats also showed a significant increase in the tissue level of malondialdehyde (MDA; p<0.01). High-dose curcumin treated diabetic rats had a significantly reduced level of MDA (p<0.05).
Conclusion: Chronic administration of curcumin could attenuate the nociceptive score in both the acute and chronic phases of the formalin test in a streptozotocin-induced experimental model of diabetes mellitus and increase thermal pain threshold. The beneficial effect of curcumin is partly attributed to attenuation of lipid peroxidation in the periphery.

Keywords

 


[1]     Tripathi BK, Srivastava AK. Diabetes mellitus: complications and therapeutics. Med Sci Monit 2006, 12(7): RA130-47.
[2]     Gleckman R, Morr J. Diabetes-related foot infections. Contemp Intern Med 1994; 6(8): 57-64.
[3]     Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract 2000; 47(2): 123-8.
[4]     Dobretsov M, Hastings SL, Romanovsky D, Stimers JR, Zhang JM. Mechanical hyperalgesia in rat models of systemic and local hyperglycemia. Brain Res 2003; 960(1-2): 174-83.
[5]     Dobretsov M, Hastings SL, Stimers JR, Zhang JM. Mechanical hyperalgesia in rats with chronic perfusion of lumbar dorsal root ganglion with hyperglycemic solution. J Neurosci Methods 2001; 110(1-2): 9-15.
[6]     Raz I, Hasdai D, Seltzer Z, Melmed RN. Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats. Diabetes 1988; 37(9): 1253-9.
[7]     Nakamura-Craig M, Follenfant RL. Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE2 and in the chronic hyperalgesia in rats with streptozotocin-induced diabetes. Pain 1995; 63(1): 33-7.
[8]     Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Ataee R, Moghaddam SN. Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain. J Med Food 2010; 13(4):821-6.
[9]     Dairam A, Fogel R, Daya S, Limson JL. Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. J Agric Food Chem 2008; 14;56(9):3350-6.
[10]  Shukla PK, Khanna VK, Ali MM, Khan MY, Srimal RC. Anti-ischemic effect of curcumin in rat brain. Neurochem Res 2008; 33(6):1036-43.
[11]  Wang Y, Yu C, Pan Y, Yang X, Huang Y, Feng Z, Li X, Yang S, Liang G. A novel synthetic mono-carbonyl analogue of curcumin, A13, exhibits anti-inflammatory effects in vivo by inhibition of inflammatory mediators. Inflammation 2012; 35(2):594-604.
[12]  Patumraj S, Wongeakin N, Sridulyakul P, Jariyapongskul A, Futrakul N, Bunnag S. Combined effects of curcumin and vitamin C to protect endothelial dysfunction in the iris tissue of STZ-induced diabetic rats. Clin Hemorheol Microcirc 2006; 35(4):481-9.
[13]  Sharma S, Chopra K, Kulkarni SK. Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF-alpha. Phytother Res 2007; 21(3):278-83.
[14]  Sharma S, Kulkarni SK, Agrewala JN, Chopra K. Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain. Eur J Pharmacol 2006; 536(3):256-61.
[15]  Zhao X, Xu Y, Zhao Q, Chen CR, Liu AM, Huang ZL. Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved. Neuropharmacology 2012; 62(2):843-54.
[16]  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 1977; 4(2):161-74.
[17]  Courteix C, Eschalier A, Lavarenne J. Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain 1993; 53(1):81-8.
[18]  Ceseña RM, Calcutt NA. Gabapentin prevents hyperalgesia during the formalin test in diabetic rats. Neurosci Lett 1999; 262(2):101-4.
[19]  Sharma S, Kulkarni SK, Chopra K. Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain. Fundam Clin Pharmacol 2007; 21(1):89-94.
[20]  Calcutt NA. Potential mechanisms of neuropathic pain in diabetes. Int Rev Neurobiol 2002; 50: 205-28.
[21]  Piercy V, Banner SE, Bhattacharyya A, Parsons AA, Sanger GJ, Smith SA, Bingham S. Thermal, but not mechanical, nociceptive behavior is altered in the Zucker Diabetic Fatty rat and is independent of glycemic status. J Diabet Complications 1999; 13(3):163-9.
[22]  Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test: characteristic biphasic pain response. Pain 1989; 38(3):347-52.
[23]  Rosland JH, Tjølsen A, Maehle B, Hole K. The formalin test in mice: effect of formalin concentration. Pain 1990; 42(2):235-42.
[24]  Yeon KY, Kim SA, Kim YH, Lee MK, Ahn DK, Kim HJ, Kim JS, Jung SJ, Oh SB. Curcumin produces an antihyperalgesic effect via antagonism of TRPV1. J Dent Res 2010; 89(2):170-4.
[25]  Tsai YM, Chien CF, Lin LC, Tsai TH. Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm 2011; 416(1):331-8.

Pathobiology Reserach
Volume 15, Issue 1
April 2012
Pages 23-32