ABSTRACT Aim: Diabetic neuropathic pain is
one of the pains which hardly respond to pharmaceutical treat. Today, various
chemical and herbal compounds have been used to reduce pain. The aim of this
study is to compare the effect of date extract and melatonin in preventing pain
in diabetic rats.Method: To study hyperalgesia response
and to compare the effect of date extract and melatonin in preventing pain, hot
plate and tail flick tests were used. After prescribing single dose of
streptozotocin to rats and approving their diabetes, treatment rats received
date extract (4ml/kg/day) or melatonin [10 mg/kg/day, intraperitoneally (i.p.)] for a
period of 6 weeks. At the end of the sixth week, control and treated rats were
examined by thermal pain response and explorative activity tests.Results: According to hot plate results, response time to thermal pain in treated group showed a
significant decrease in comparison with the control group (P<0.01). Prescription of date
extract increased response time to thermal pain in comparison with treated
group (P<0.01), so that response time
approximated to control group. Although melatonin approximated to the response
time to control group, the significant difference was not observed among
melatonin receivers and other groups. In the assessment of diabetic neuropathy
on the explorative activity of rats in an open field behavioral test, total
distance moved and rearing frequency were significantly decreased, while
administration of date extract did also improve motor deficits induced by STZ. Conclusions:Findings of this study showed that date extract
decreased thermal hyperalgesia and can prevent pain resulted from diabetic
Cite this paper
Shabani, M. , Zangiabadi, N. and Asadi-Shekaari, M. (2013) Evidence for Positive Effects of Date Extract That Attenuates Thermal Hyperalgesia in a Diabetic Rat Model of Neuropathic Pain. Neuroscience and Medicine, 4, 16-22. doi: 10.4236/nm.2013.41003.
 C. Clark and D. Lee, “Prevention and Treatment of the Complications of Diabetes Mellitus,” New England Journal of Medicine, Vol. 332, No. 18, 1995, p. 1210.
 S. Sharma, et al., “Curcumin Attenuates Thermal Hyperalgesia in a Diabetic Mouse Model of Neuropathic Pain,” European Journal of Pharmacology, Vol. 536, No. 3, 2006, pp. 256-261. doi:10.1016/j.ejphar.2006.03.006
 M. Brown and A. Asbury, “Diabetic Neuropathy,” Annals of Neurology, Vol. 15, No. 1, 1984, pp. 2-12.
 J. Flier, et al., “Sorbitol, Phosphoinositides, and SodiumPotassium-ATPase in the Pathogenesis of Diabetic Complications,” New England Journal of Medicine, Vol. 316, No. 10, 1987, pp. 599-606.
 J. Lynch III, M. Jarvis and E. Kowaluk, “An Adenosine Kinase Inhibitor Attenuates Tactile Allodynia in a Rat Model of Diabetic Neuropathic Pain,” European Journal of Pharmacology, Vol. 364, No. 2-3, 1999, pp. 141-146.
 N. Aksoy, et al., “Effects of Melatonin on OxidativeAntioxidative Status of Tissues in Streptozotocin Induced Diabetic Rats,” Cell Biochemistry and Function, Vol. 21, No. 2, 2003, pp. 121-125. doi:10.1002/cbf.1006
 H. Vural, et al., “Melatonin Inhibits Lipid Peroxidation and Stimulates the Antioxidant Status of Diabetic Rats,” Journal of Pineal Research, Vol. 31, No. 3, 2001, pp. 193-198. doi:10.1034/j.1600-079X.2001.310301.x
 E. Saafi, et al., “Protective Effect of Date Palm Fruit Extract (Phoenix dactylifera L.) on Dimethoate InducedOxidative Stress in Rat Liver,” Experimental and Toxicologic Pathology, Vol. 63, No. 5, 2011, pp. 433-441.
 P. Montilla, et al., “Oxidative Stress in Diabetic Rats Induced by Streptozotocin: Protective Effects of Melatonin,” Journal of Pineal Research, Vol. 25, No. 2, 1998, pp. 94-100. doi:10.1111/j.1600-079X.1998.tb00545.x
 E. Peschke, et al., “Receptor (MT1) Mediated Influence of Melatonin on cAMP Concentration and Insulin Secretion of Rat Insulinoma Cells INS 1,” Journal of Pineal Research, Vol. 33, No. 2, 2002, pp. 63-71.
 R. Arreola-Espino, et al., “Melatonin Reduces FormalinInduced Nociception and Tactile Allodynia in Diabetic Rats,” European Journal of Pharmacology, Vol. 577, No. 1-3, 2007, pp. 203-210. doi:10.1016/j.ejphar.2007.09.006
 D. Tan, et al., “One Molecule, Many Derivatives: A Never Ending Interaction of Melatonin with Reactive Oxygen and Nitrogen Species?” Journal of Pineal Research, Vol. 42, No. 1, 2007, pp. 28-42.
 P. Vayalil, “Antioxidant and Antimutagenic Properties of Aqueous Extract of Date Fruit (Phoenix dactylifera L. Arecaceae),” Journal of Agricultural and Food Chemistry, Vol. 50, No. 3, 2002, pp. 610-617. doi:10.1021/jf010716t
 A. Sallal and A. Ashkenani, “Effect of Date Extract on Growth and Spore Germination of Bacillus subtilis,” Microbios, Vol. 59, No. 240-241, 1989, p. 203.
 W. Al-Shahib and R. Marshall, “The Fruit of the Date Palm: Its Possible Use as the Best Food for the Future?” International Journal of Food Sciences and Nutrition, Vol. 54, No. 4, 2003, pp. 247-259.
 H. Mirheydar, “Consumption of Plants in Prevention and Treatment of Disease,” Vol. 2, Tehran University, Persian, 1995, pp. 21-60.
 J. Malone, et al., “The Effect of Hyperglycemia on Nerve Conduction and Structure Is Age Dependent,” Diabetes, Vol. 45, No. 2, 1996, p. 209.
 D. Sigaudo-Roussel, B. Fromy and J. L. Saumet, “Diabetic Neuropathy in Animal Models,” Drug Discovery Today: Disease Models, Vol. 4, No. 1, 2007, pp. 39-44.
 S. Usuki, et al., “Effect of Pre-Germinated Brown Rice Intake on Diabetic Neuropathy in Streptozotocin-Induced Diabetic Rats,” Nutrition & Metabolism, Vol. 4, No. 1, 2007, p. 25. doi:10.1186/1743-7075-4-25
 E. Liepinsh, et al., “Protective Effects of Mildronate in an Experimental Model of Type 2 Diabetes in Goto Kakizaki Rats,” British Journal of Pharmacology, Vol. 157, No. 8, 2009, pp. 1549-1556.
 S. Sharma, S. Kulkarni and K. Chopra, “Effect of Resveratrol, a Polyphenolic Phytoalexin, on Thermal Hyperalgesia in a Mouse Model of Diabetic Neuropathic Pain,” Fundamental & Clinical Pharmacology, Vol. 21, No. 1, 2007, pp. 89-94. doi:10.1111/j.1472-8206.2006.00455.x
 M. Shabani, et al., “Walnut Consumption Protects Rats against Cisplatin-Induced Neurotoxicity,” NeuroToxicology, Vol. 33, No. 5, 2012, pp. 1314-1321.
 M. Shabani, et al., “Profound Destructive Effects of Adolescent Exposure to Vincristine Accompanied with Some Sex Differences in Motor and Memory Performance,” Canadian Journal of Physiology and Pharmacology, Vol. 90, No. 4, 2012, pp. 379-386. doi:10.1139/y11-132
 M. Razavinasab, et al., “Pharmacological Blockade of TRPV1 Receptors Modulates the Effects of 6-OHDA on Motor and Cognitive Functions in a Rat Model of Parkinson’s Disease,” Fundamental & Clinical Pharmacology, 2012. doi:10.1111/fcp.12015
 N. Zangiabadi, et al., “Date Fruit Extract Is a Neuroprotective Agent in Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats: A Multimodal Analysis,” Oxidative Medicine and Cellular Longevity, 2011, Article ID: 976948. doi:10.1155/2011/976948
 M. Shabani, et al., “Evaluation of Destructive Effects of Exposure to Cisplatin during Developmental Stage: No Profound Evidence for Sex Differences in Impaired Motor and Memory Performance,” The International Journal of Neuroscience, Vol. 122, No. 8, 2012, pp. 439-448.
 B. Galer, A. Gianas and M. Jensen, “Painful Diabetic Polyneuropathy: Epidemiology, Pain Description, and Quality of Life,” Diabetes Research and Clinical Practice, Vol. 47, No. 2, 2000, pp. 123-128.
 M. Serpell, “Anatomy, Physiology and Pharmacology of Pain,” Anaesthesia &Intensive Care Medicine, Vol. 6, No. 1, 2005, pp. 7-10. doi:10.1383/anes.126.96.36.199133
 E. Peschke, “Melatonin, Endocrine Pancreas and Diabetes,” Journal of Pineal Research, Vol. 44, No. 1, 2008, pp. 26-40.
 M. Tuzcu and G. Baydas, “Effect of Melatonin and Vitamin E on Diabetes-Induced Learning and Memory Impairment in Rats,” European Journal of Pharmacology, Vol. 537, No. 1-3, 2006, pp. 106-110.
 D. Kooyenga, et al., “Palm Oil Antioxidant Effects in Patients with Hyperlipidaemia and Carotid Stenosis: 2 Year Experience,” Asia Pacific Journal of Clinical Nutrition, Vol. 6, No. 1, 1997, pp. 72-75.
 T. Ng, et al., “Nonhypercholesterolemic Effects of a Palm-Oil Diet in Malaysian Volunteers,” American Journal of Clinical Nutrition, Vol. 53, No. 4, 1991, p. 1015S.
 K. Sundram, T. Karupaiah and K. Hayes, “Stearic AcidRich Interesterified Fat and Trans-Rich Fat Raise the LDL/HDL Ratio and Plasma Glucose Relative to Palm Olein in Humans,” Nutrition & Metabolism, Vol. 4, No. 3, 2007, p. 3.
 M. Al-Farsi, et al., “Compositional and Sensory Characteristics of Three Native Sun-Dried Date (Phoenix dactylifera L.) Varieties Grown in Oman,” Journal of Agricultural and Food Chemistry, Vol. 53, No. 19, 2005, pp. 7586-7591.
 A. Allaith, “Antioxidant Activity of Bahraini Date Palm (Phoenix dactylifera L.) Fruit of Various Cultivars,” International Journal of Food Science & Technology, Vol. 43, No. 6, 2008, pp. 1033-1040.
 J. Podratz, E. Rodriguez and A. Windebank, “Antioxidants Are Necessary for Myelination of Dorsal Root Ganglion Neurons, in Vitro,” Glia, Vol. 45, No. 1, 2004, pp. 54-58. doi:10.1002/glia.10302
 P. van Dam, et al., “Nerve Function and Oxidative Stress in Diabetic and Vitamin E-Deficient Rats,” Free Radical Biology and Medicine, Vol. 24, No. 1, 1998, pp. 18-26.
 M. Backonja, “Defining Neuropathic Pain,” Anesthesia & Analgesia, Vol. 97, No. 3, 2003, p. 785.
 S. Sayyed, A. Kumar and S. Sharma, “Effects of U83836 E on Nerve Functions, Hyperalgesia and Oxidative Stress in Experimental Diabetic Neuropathy,” Life Sciences, Vol. 79, No. 8, 2006, pp. 777-783.
 H. Kim, et al., “Analgesic Effect of Vitamin E Is Mediated by Reducing Central Sensitization in Neuropathic Pain,” Pain, Vol. 122, No. 2, 2006, pp. 53-62.
 G. Baydas, H. Canatan and A. Turkoglu, “Comparative Analysis of the Protective Effects of Melatonin and Vitamin E on Streptozocin-Induced Diabetes Mellitus,” Atherosclerosis, Vol. 2, 2002, pp. 8-10.
 M. Devi, Y. Suresh and U. Das, “Preservation of the Antioxidant Status in Chemically-Induced Diabetes Mellitus by Melatonin,” Journal of Pineal Research, Vol. 29, No. 2, 2000, pp. 108-115.
 A. Maritim, R. Sanders and J. Watkins III, “Diabetes, Oxidative Stress, and Antioxidants: A Review,” Journal of Biochemical and Molecular Toxicology, Vol. 17, No. 1, 2003, pp. 24-38. doi:10.1002/jbt.10058
 M., Ebadi, et al., “Pineal Opioid Receptors and Analgesic Action of Melatonin,” Journal of Pineal Research, Vol. 24, No. 4, 1998, pp. 193-200.
 G. Maestroni, A. Conti and W. Pierpaoli, “Role of the Pineal Gland in Immunity: II. Melatonin Enhances the Antibody Response via an Opiatergic Mechanism,” Clinical and Experimental Immunology, Vol. 68, No. 2, 1987, p. 384.