Neuropharmacology and analgesiaEffect of curcumin on diabetic peripheral neuropathic pain: Possible involvement of opioid system
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.
References (29)
- et al.
Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases
Int. J. Biochem. Cell Biol.
(2009) - et al.
Lithium attenuates pain-related behavior in a rat model of neuropathic pain: possible involvement of opioid system
Pharmacol. Biochem. Behav.
(2012) Experimental models of painful diabetic neuropathy
J. Neurol. Sci.
(2004)- et al.
Quantitative assessment of tactile allodynia in the rat paw
J. Neurosci. Methods
(1994) - et al.
RP-67580, a specific tachykinin NK1 receptor antagonist, relieves chronic hyperalgesia in diabetic rats
Eur. J. Pharmacol.
(1993) - et al.
Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat
Pain
(1999) - et al.
Ethosuximide reduces allodynia and hyperalgesia and potentiates morphine effects in the chronic constriction injury model of neuropathic pain
Eur. J. Pharmacol.
(2012) - et al.
Curcumin mediates time and concentration dependent regulation of redox homeostasis leading to cytotoxicity in macrophage cells
Eur. J. Pharmacol.
(2009) - et al.
A pharmacologic analysis of mechanical hyperalgesia in streptozotocin/diabteic rats
Pain
(1998) Descending control of pain
Prog. Neurobiol.
(2002)
Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain
Eur. J. Pharmacol.
The effect of progesterone on expression and development of neuropathic pain in a rat model of peripheral neuropathy
Eur. J. Pharmacol.
Differential behavioral outcomes in the sciatic cryoneurolysis model of neuropathic pain in rats
Pain
β2-adrenoceptor and insulin receptor expression in the skeletal muscle of streptozotocin induced diabetic rats: antagonism by vitamin D3 and curcumin
Eur. J. Pharmacol
Cited by (79)
Bioactive compounds for neuropathic pain: An update on preclinical studies and future perspectives
2022, Journal of Nutritional BiochemistryEffects of turmeric (Curcuma longa) and its constituent (curcumin) on the metabolic syndrome: An updated review
2022, Journal of Integrative MedicineReduced sexual motivation of diabetic female rats: Restoration with insulin
2021, Hormones and BehaviorRecent advances of nanomedicine-based strategies in diabetes and complications management: Diagnostics, monitoring, and therapeutics
2021, Journal of Controlled ReleaseThe pivotal role of nuclear factor erythroid 2-related factor 2 in diabetes-induced endothelial dysfunction
2020, Pharmacological Research