Elsevier

European Journal of Pharmacology

Volume 723, 15 January 2014, Pages 202-206
European Journal of Pharmacology

Neuropharmacology and analgesia
Effect of curcumin on diabetic peripheral neuropathic pain: Possible involvement of opioid system

https://doi.org/10.1016/j.ejphar.2013.11.033Get rights and content

Abstract

Neuropathic pain is one of the most common complications of diabetes mellitus. As efficacy and tolerability of current therapy for neuropathic pain are not ideal, we need to develop the novel drug for better treatment. Curcumin as a natural flavonoid from Curcuma longa has considerable effects on nervous system such as, antidepressant, antinociceptive and neuroprotective effects. The present study was designed to investigate the effect of curcumin on diabetic peripheral neuropathic pain and possible involvement of opioid system. A single dose of 60 mg/kg streptozotocin was injected intraperitoneally to induce diabetes in rats. STZ-induced diabetic rats were treated with curcumin (50 mg/kg/day) acute and chronically. Thermal hyperalgesia and mechanical allodynia were measured on the days 0, 7, 14 and 21 after diabetes induction as behavioral scores of neuropathic pain. Chronic, but not acute, treatment with curcumin prevents the weight loss and attenuates mechanical allodynia in STZ-induced diabetic rats. Pretreatment with naloxone (1 mg/kg) significantly reduced anti-allodynic effect of chronic curcumin in von Frey filament test. Our results suggest that curcumin can be considered as a new therapeutic potential for the treatment of diabetic neuropathic pain and the activation of opioid system may be involved in the antinociceptive effect of curcumin.

Introduction

Neuropathic pain is one of the most common complications of diabetes mellitus. Diabetic peripheral neuropathic pain involves the deep muscular aches, lancinating pains and a persistent burning or tingling sensation, usually in the legs and feet. Patients with diabetic peripheral neuropathic pain may also experience allodynia and hyperalgesia (Ziegler, 2008). As efficacy and tolerability of current therapy for Diabetic neuropathic pain are not ideal, we need to develop the novel drug for better treatment of this chronic disease (Spallone et al., 2012). Curcumin, a natural flavonoid from Curcuma longa, is a major component of turmeric and exhibits a wide range of therapeutic effects such as anticarcinogenic, antioxidant, antimicrobial and neuroprotective properties (Lopresti et al., 2012). Safety evaluation studies indicate that both turmeric and curcumin are well tolerated at high dose ranges without any toxic effects. Thus, both turmeric and curcumin have potential in the development of modern medicine for treatment of various diseases (Park et al., 2012). It is well known that curcumin decreases the inflammatory responses through inhibition of cyclooxygenase 2, lipoxygenase 5 and nitric oxide synthase (Zhou et al., 2011). In addition, the antinociceptive effects of curcumin have been demonstrated in different pain models such as orofacial and inflammatory pain (Mittal et al., 2009, Park et al., 2012). Recently, it was also shown that curcumin exerts anti-hyperalgesic effects in a mouse model of neuropathic pain (Zhao et al., 2012). The antinociceptive mechanisms of curcumin have not been well understood. A few studies suggest the role of delta and mu-opioid receptors in antinociceptive effect of curcumin (Tajik et al., 2007, Zhao et al., 2012). Taken together the present study was designed to investigate the effect of curcumin on diabetic peripheral neuropathic pain and possible involvement of opioid system in this effect.

Section snippets

Animals

Experiments were carried out on Male albino Wistar rats (Pasteur's institute, Tehran, Iran) weighing 220–280 g. Three to four rats were housed in a cage under a 12 h light/dark cycle with food and water available ad libitum. Procedures involving animals and their care were conducted in conformity with National Institutes of Health guidelines for the care and use of laboratory animals.

Drugs and reagents

Streptozotocin, curcumin and naloxone were purchased from Sigma (St Louis, MO, USA).Glucose oxidase peroxidase kit

Effects of treatment on blood glucose and body weight

Streptozotocin (STZ) injection induced a significant increase in plasma glucose levels in comparison with control animal. Treatment with curcumin did not reduce hyperglycemia in diabetic rats significantly (Fig. 1). As shown in Fig. 2, there was a significant decrease in the body weight of diabetic rats as compared with aged matched control animals (F3,35=72.1, P<0.001). Chronic administration of curcumin from 2nd to 4th week significantly prevented weight loss in diabetic rats.

Effects of treatment on heat hyperalgesia

Surprisingly,

Discussion

The present study shows that STZ-induced diabetes in rats leads to mechanical allodynia, but not thermal hyperalgesia. Mechanical allodynia started 7 days after STZ injection and persisted for 21 days. Our results, whilst confirming that diabetic rats developed hypersensitivity to mechanical stimulation of von Frey filament, showed a concomitant increase in withdrawal latency to radiant heat stimuli, indicating thermal hypoalgesia in STZ-induced diabetic rats. This is in agreement with some

Acknowledgments

This paper has been taken out from the MD degree thesis and supported financially by Vice Chancellor of Research, Kashan University of Medical Sciences, Kashan, Iran.

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