Review Article

Curcumin and its Multi-target Function Against Pain and Inflammation: An Update of Pre-clinical Data

Author(s): Shaikh Jamal Uddin*, Md. Fahim Hasan, Mohasana Afroz, Dipto Kumer Sarker, Razina Rouf, Muhammad Torequl Islam, Jamil A. Shilpi and Mohammad S. Mubarak*

Volume 22 , Issue 6 , 2021

Published on: 25 September, 2020

Page: [656 - 671] Pages: 16

DOI: 10.2174/1389450121666200925150022

Price: $65


Pain is an unpleasant sensation that has complex and varying causative etiology. Modern drug discovery focuses on identifying potential molecules that target multiple pathways with a safer profile compared to those with a single target. The current treatment of pain and inflammation with the available therapeutics has a number of major side effects. Pain is one of the major clinical problems that need functional therapeutics which act on multiple targets and with low toxicity. Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has been used for years in Ayurvedic, Chinese, and in many other systems of traditional medicine. Pre-clinical data published thus far demonstrated that curcumin possesses multi-target biological functions, suggesting its potential use to cure different diseases. However, there is no or very brief systematic review of its potential use in pain and inflammation with underlying mechanisms for such activities. Accordingly, the aim of the current review was to update the pre-clinical data of curcumin and its multiple targeting pathways for analgesic and anti-inflammatory effects, and to further propose a molecular mechanism(s). A literature study was conducted using different known databases, including Pubmed, SciFinder, Google Scholar, and Science Direct. Available pre-clinical data suggest the ameliorating effect of curcumin in pain and inflammation is rendered through the modulation of pain pathways, including inhibition of a number of pro-inflammatory mediators, inhibition of oxidative stress and cyclooxygenase-2 (COX-2), down-regulation of Ca2+/calmodulin-depend protein kinase II (CaMKIIα) and calcium channels like transient receptor potential (TRP), modulation of metabotropic glutamate receptor-2 (mGlu2), modulation of monoamine system, inhibition of JAK2/STAT3 signaling pathway, remodeling of extracellular matrix proteins, inhibition of apoptosis, inhibition of JNK/MAPK and ERK/CREB signaling pathway, and activation of the opioid system. Taken all together, it is evident that curcumin is one of the promising, safe, and natural polyphenolic molecules that target multiple molecular pathways in pain and can be beneficial in the treatment and management of pain and inflammation.

Keywords: Curcumin, multi-target pharmacology, Curcuma longa, pain, inflammation, phytoconstituents.

Graphical Abstract
Bonica JJ. The need of a taxonomy. Pain 1979; 6(3): 247-8.
[] [PMID: 460931]
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009; 139(2): 267-84.
[] [PMID: 19837031]
Kuner R. Central mechanisms of pathological pain. Nat Med 2010; 16(11): 1258-66.
[] [PMID: 20948531]
Luo C, Kuner T, Kuner R. Synaptic plasticity in pathological pain. Trends Neurosci 2014; 37(6): 343-55.
[] [PMID: 24833289]
Hwang SH, Wecksler AT, Wagner K, Hammock BD. Rationally designed multitarget agents against inflammation and pain. Curr Med Chem 2013; 20(13): 1783-99.
[] [PMID: 23410172]
Talevi A. Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective. Front Pharmacol 2015; 6(205): 205.
[] [PMID: 26441661]
Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci 2006; 78(18): 2081-7.
[] [PMID: 16413584]
Lestari ML, Indrayanto G. Curcumin. Profiles Drug Subst Excip Relat Methodol 2014; 39: 113-204.
[] [PMID: 24794906]
Mahady GB, Pendland SL, Yun G, Lu ZZ. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 2002; 22(6C): 4179-81.
[PMID: 12553052]
Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN. Curcumin for malaria therapy. Biochem Biophys Res Commun 2005; 326(2): 472-4.
[] [PMID: 15582601]
Vera-Ramirez L, Pérez-Lopez P, Varela-Lopez A, Ramirez-Tortosa M, Battino M, Quiles JL. Curcumin and liver disease. Biofactors 2013; 39(1): 88-100.
[] [PMID: 23303639]
Wright LE, Frye JB, Gorti B, Timmermann BN, Funk JL. Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer. Curr Pharm Des 2013; 19(34): 6218-25.
[] [PMID: 23448448]
Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin: miniperspective. J Med Chem 2017; 60(5): 1620-37.
[] [PMID: 28074653]
Wang R, Li J, Zhao Y, Li Y, Yin L. Investigating the therapeutic potential and mechanism of curcumin in breast cancer based on RNA sequencing and bioinformatics analysis. Breast Cancer 2018; 25(2): 206-12.
[] [PMID: 29139094]
Cao J, Wang T, Wang M. Investigation of the anti-cataractogenic mechanisms of curcumin through in vivo and in vitro studies. BMC Ophthalmol 2018; 18(1): 48.
[] [PMID: 29454324]
Panahi Y, Hosseini MS, Khalili N, et al. Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial. Biomed Pharmacother 2016; 82: 578-82.
[] [PMID: 27470399]
Mazzolani F, Togni S. Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study. Clin Ophthalmol 2013; 7: 939-45.
[PMID: 23723686]
Allegri P, Mastromarino A, Neri P. Management of chronic anterior uveitis relapses: efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin Ophthalmol 2010; 4: 1201-6.
[PMID: 21060672]
Xiao L, Ding M, Fernandez A, Zhao P, Jin L, Li X. Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors. Eur Cell Mater 2017; 33: 279-93.
[] [PMID: 28485773]
Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett 2008; 267(1): 133-64.
[] [PMID: 18462866]
Chen J-J, Dai L, Zhao L-X, Zhu X, Cao S, Gao Y-J. Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis. Sci Rep 2015; 5: 10278.
[] [PMID: 25988362]
Drobnic F. Curcumin reduces pain in DOMS. Pain 2016; 157(10): 2390-1.
[] [PMID: 27643838]
Cheppudira B, Fowler M, McGhee L, et al. Curcumin: a novel therapeutic for burn pain and wound healing. Expert Opin Investig Drugs 2013; 22(10): 1295-303.
[] [PMID: 23902423]
Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann N Y Acad Sci 2005; 1056(1): 206-17.
[] [PMID: 16387689]
Motaghinejad M, Karimian M, Motaghinejad O, Shabab B, Yazdani I, Fatima S. Protective effects of various dosage of Curcumin against morphine induced apoptosis and oxidative stress in rat isolated hippocampus. Pharmacol Rep 2015; 67(2): 230-5.
[] [PMID: 25712644]
Gaffey A, Campbell J, Porritt K, Slater H. The effects of curcumin on musculoskeletal pain: a systematic review protocol. JBI Database Syst Rev Implement Reports 2015; 13(2): 59-73.
[] [PMID: 26447034]
Domenico C, Linsenbardt H, Haney R, Meagher M. (544) Evaluating the anti-hyperalgesic and anti-inflammatory potential of curcumin in a human model of experimental pain. J Pain 2015; 16(4): S112.
Henrotin Y, Gharbi M, Dierckxsens Y, et al. Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial. BMC Complement Altern Med 2014; 14: 159.
[] [PMID: 24886572]
Drobnic F, Riera J, Appendino G, et al. Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva®): a randomised, placebo-controlled trial. J Int Soc Sports Nutr 2014; 11: 31.
[] [PMID: 24982601]
Gupte PA, Giramkar SA, Harke SM, et al. Evaluation of the efficacy and safety of Capsule Longvida® Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study. J Inflamm Res 2019; 12: 145-52.
[] [PMID: 31239749]
Jia T, Rao J, Zou L, et al. Nanoparticle-encapsulated curcumin inhibits diabetic neuropathic pain involving the P2Y12 receptor in the dorsal root ganglia. Front Neurosci 2018; 11: 755.
[] [PMID: 29422835]
Peng KT, Chiang YC, Huang TY, Chen PC, Chang PJ, Lee CW. Curcumin nanoparticles are a promising anti-bacterial and anti-inflammatory agent for treating periprosthetic joint infections. Int J Nanomedicine 2019; 14: 469-81.
[] [PMID: 30666108]
Pieretti S, Ranjan AP, Di Giannuario A, et al. “Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice”. Colloids Surf B Biointerfaces 2017; 158: 379-86.
[] [PMID: 28719859]
Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health 2011; 11: 770.
[] [PMID: 21978149]
Dureja GP, Iyer RN, Das G, Ahdal J, Narang P. Evidence and consensus recommendations for the pharmacological management of pain in India. J Pain Res 2017; 10: 709-36.
[] [PMID: 28435313]
Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers 2017; 3: 17002.
[] [PMID: 28205574]
Childs JD, Cleland JA, Elliott JM, et al. American Physical Therapy Association. Neck pain: Clinical practice guidelines linked to the International Classification of Functioning, Disability, and Health from the Orthopedic Section of the American Physical Therapy Association. J Orthop Sports Phys Ther 2008; 38(9): A1-A34.
[] [PMID: 18758050]
Douglass AB, Bope ET. Evaluation and treatment of posterior neck pain in family practice. J Am Board Fam Pract 2004; 17(Suppl.): S13-22.
[] [PMID: 15575026]
Pop-Busui R, Ang L, Holmes C, Gallagher K, Feldman EL. Inflammation as a Therapeutic Target for Diabetic Neuropathies. Curr Diab Rep 2016; 16(3): 29.
[] [PMID: 26897744]
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.
[] [PMID: 16584726]
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.
[] [PMID: 17199240]
Li Y, Zhang Y, Liu DB, Liu HY, Hou WG, Dong YS. Curcumin attenuates diabetic neuropathic pain by downregulating TNF-α in a rat model. Int J Med Sci 2013; 10(4): 377-81.
[] [PMID: 23471081]
Adhikari R, Jyothi Y, Bora D, Vamsee Veena A. Combined effect of aqueous extract of curcuma longa linn. with metformin in diabetes induced neuroptahic pain in rats. Asian J Pharm Clin Res 2015; 8(5): 166-70.
Meng B, Shen LL, Shi XT, et al. Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain. Neurosci Lett 2015; 605: 59-64.
[] [PMID: 26282904]
Ahmed MF, Abdallah MA, Ibrahim AM. Effect of Curcumin on Diabetic Neuropathy in Streptozotocin Induced Diabetes in Rats. Life Sci J 2015; 12(12)
Mittal N, Joshi R, Hota D, Chakrabarti A. Evaluation of antihyperalgesic effect of curcumin on formalin-induced orofacial pain in rat. Phytother Res 2009; 23(4): 507-12.
[] [PMID: 19051211]
Bulboacă AE, Bolboacă SD, Stănescu IC, Sfrângeu CA, Bulboacă AC. Preemptive analgesic and antioxidative effect of curcumin for experimental migraine BioMed Res Int 2017.
Ikawati Z, Yuniarti N, Margono SA. The analgesic effect of a curcumin analogue 1, 5-bis (4′-hydroxy-3′-methoxyphenyl)-1, 4-pentadien-3-on (Gamavuton-0) in acute and persistent pain. J Appl Pharm Sci 2014; 4(8): 48.
Attia HN, Al-Rasheed NM, Al-Rasheed NM, Maklad YA, Ahmed AA, Kenawy SAB. Protective effects of combined therapy of gliclazide with curcumin in experimental diabetic neuropathy in rats. Behav Pharmacol 2012; 23(2): 153-61.
[] [PMID: 22411174]
BHASKAR NAGILLA PRK. Neuroprotective and antinociceptive effect of curcumin in diabetic neuropathy in rats. Int J Pharm Pharm Sci 2014; 6(5): 131-8.
Zheng Z, Sun Y, Liu Z, Zhang M, Li C, Cai H. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. Drug Des Devel Ther 2015; 9: 4931-42.
[PMID: 26345159]
Zhang Z, Leong DJ, Xu L, et al. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther 2016; 18(1): 128.
[] [PMID: 27260322]
Costa GMF. Leite CMdA. Trigeminal neuralgia: peripheral and central mechanisms. Rev Dor 2015; 16: 297-301.
Zhang L, Ding X, Wu Z, Wang M, Tian M. Curcumin alleviates pain and improves cognitive impairment in a rat model of cobra venom-induced trigeminal neuralgia. J Pain Res 2018; 11: 1095-104.
[] [PMID: 29950886]
Areti A, Yerra VG, Naidu V, Kumar A. Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol 2014; 2: 289-95.
[] [PMID: 24494204]
El Sheikh WM, Alahmar IE, Salem GM, El-Sheikh MA. Tumor necrosis factor alpha in peripheral neuropathy in type 2 diabetes mellitus. Egypt J Neurol Psychiat Neurosurg 2019; 55(1): 37.
Chen X, Andresen BT I, Hill M, Zhang J, Booth F, Zhang C. Role of Reactive Oxygen Species in Tumor Necrosis Factor-alpha Induced Endothelial Dysfunction. Curr Hypertens Rev 2008; 4(4): 245-55.
[] [PMID: 20559453]
Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord 2008; 9(4): 301-14.
[] [PMID: 18709457]
Zhang X, Guan Z, Wang X, et al. Curcumin alleviates oxaliplatin-induced peripheral neuropathic pain through inhibiting oxidative stress-mediated activation of NF-κB and mitigating inflammation. Biol Pharm Bull 2020; 43(2): 348-55.
[] [PMID: 31776306]
Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Therapeutic role of curcumin in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals. Neurosci Lett 2012; 511(1): 18-22.
[] [PMID: 22281447]
Babu A, Prasanth KG, Balaji B. Effect of curcumin in mice model of vincristine-induced neuropathy. Pharm Biol 2015; 53(6): 838-48.
[] [PMID: 25429779]
Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K. Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. J Agric Food Chem 2007; 55(25): 10150-5.
[] [PMID: 18001039]
Luca A, Alexa T, Dondaş A, et al. Pain modulation by curcumin and ascorbic acid in mice. Rev Med Chir Soc Med Nat Iasi 2014; 118(2): 346-51.
[PMID: 25076698]
Tamaddonfard E, Tajik H, Hamzeh-Gooshchi N. Effects of curcumin and vitamin C on visceral nociception induced by acetic acid in rats. Med Weter 2008; 64: 883-5.
Haider S, Naqvi F, Tabassum S, et al. Preventive effects of curcumin against drug- and starvation-induced gastric erosions in rats. Sci Pharm 2013; 81(2): 549-58.
[] [PMID: 23833720]
Kim J-H, Jin S, Kwon HJ, Kim BW. Curcumin blocks naproxen-induced gastric antral ulcerations through inhibition of lipid peroxidation and activation of enzymatic scavengers in rats. J Microbiol Biotechnol 2016; 26(8): 1392-7.
[] [PMID: 27197667]
Kellogg AP, Cheng HT, Pop-Busui R. Cyclooxygenase-2 pathway as a potential therapeutic target in diabetic peripheral neuropathy. Curr Drug Targets 2008; 9(1): 68-76.
[] [PMID: 18220714]
McCarthy D. Prostaglandins, COX-2, and sensory perception. Gut 2000; 47(Suppl. 4): iv66-8.
[] [PMID: 11076921]
Moini Zanjani T, Ameli H, Labibi F, Sedaghat K, Sabetkasaei M. The attenuation of pain behavior and serum COX-2 concentration by curcumin in a rat model of neuropathic pain. Korean J Pain 2014; 27(3): 246-52.
[] [PMID: 25031810]
Zhu X, Li Q, Chang R, et al. Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model. PLoS One 2014; 9(3): e91303.
[] [PMID: 24603592]
Schembri E. Are Opioids Effective in Relieving Neuropathic Pain? SN Comprehen Clin Med 2019; 1(1): 30-46.
Balogh M, Zádor F, Zádori ZS, et al. Efficacy-Based Perspective to Overcome Reduced Opioid Analgesia of Advanced Painful Diabetic Neuropathy in Rats. Front Pharmacol 2019; 10(347): 347.
[] [PMID: 31024314]
Banafshe HR, Hamidi GA, Noureddini M, Mirhashemi SM, Mokhtari R, Shoferpour M. Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement of opioid system. Eur J Pharmacol 2014; 723: 202-6.
[] [PMID: 24315931]
Tajik H, Tamaddonfard E, Hamzeh-Gooshchi N. The effect of curcumin (active substance of turmeric) on the acetic acid-induced visceral nociception in rats. Pak J Biol Sci 2008; 11(2): 312-4.
[] [PMID: 18817212]
Sugimoto K, Yasujima M, Yagihashi S. Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des 2008; 14(10): 953-61.
[] [PMID: 18473845]
Shi X, Xia X, Cao H, Jiajia L, Shaosheng W, Jun L. Effects of curcumin on expression of receptor for advanced glycation end-products in spinal dorsal horn and dorsal root ganglion of rats with type 2 diabetic neuropathic pain. Chinese J Anesthesiol 2014; 34(10): 1207-10.
Purves T, Middlemas A, Agthong S, et al. A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy. FASEB J 2001; 15(13): 2508-14.
[] [PMID: 11689477]
Jeon Y, Kim C-E, Jung D, et al. Curcumin could prevent the development of chronic neuropathic pain in rats with peripheral nerve injury. Curr Ther Res Clin Exp 2013; 74: 1-4.
[] [PMID: 24385078]
Lv J, Cao L, Zhang R, Bai F, Wei P. A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1. Acta Cir Bras 2018; 33(6): 533-41.
[] [PMID: 30020315]
Zhou L, Yuan C, Shi X, Zheng C, Lian Q, Jun L, et al. Effect of curcumin on expression of p-ERK and p-CREB in spinal dorsal horn and dorsal root ganglion in type 2 diabetic neuropathic pain in rats. Chinese J Anesthesiol 2013; 33(8): 928-31.
HUANG C-c. CHEN G, WU Y, LIAN Q-q, LI J, CAO H. Effect of curcumin on p-ERK1/2-AP-1 cascade and diabetic neuropathic pain in rats Chinese J Pathophysiol 2011; 22(6)
Jeon Y, Ha J, Yeo J, Kim Y. The Effect of Curcumin on Neuropathic Pain Induced by Chronic Sciatic Nerve Ligation in Rats. Anesthesiol 2008; 109: A748.
Cao H, He L, Lian Q. Effects and Mechanism of Curcumin on the Neuropathic Pain in Rats with Ligation of Sciatic Nerve American Society of Anesthesiologists Annual Meeting Scientific Abstracts A1154.
Li J, Wu J, Cao H, Lian Q. Effect and Mechanisms of Curcumin on JNK in Spinal Cord and DRG on Inflammatory Pain in Rats American Society of Anesthesiologists Annual Meeting Scientific Abstracts A1276.
Mun SH, Kim HS, Kim JW, et al. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway. J Pharmacol Sci 2009; 111(1): 13-21.
[] [PMID: 19763044]
Tolkovsky A. Apoptosis in diabetic neuropathy International Review of Neurobiology 50. Academic Press 2002; pp. 145-59.
Jafari Anarkooli I, Sankian M, Ahmadpour S, Varasteh A-R, Haghir H. Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats. Exp Diabetes Res 2008; 2008: 638467.
[] [PMID: 18923682]
LI J. CHEN G, HUANG C-c, LI J. Effects and Mechanisms of Curcumin on Neuron Apoptosis and Pain Threshold in Diabetic Neuropathic Pain Rats American Society of Anesthesiologists Annual Meeting Scientific Abstracts A1630.
Cao H, Chen G, Huang C, Song X, Li J. Neuroprotective of Curcumin and Vit. B Against Apoptotic Cell Death in Diabetic Neuropathic Pain Rats American Society of Anesthesiologists Annual Meeting Scientific Abstracts A1237.
Chen G, Huang C, Dang J, Lian Q, Jun L, Cao H. Effect of curcumin on apoptosis in spinal cord and dorsal root ganglion neurons in a rat model of diabetic neuropathic pain. Chinese J Anesthesiol 2011; 31(4): 435-8.
Yang F, Yu J, Ke F, et al. Curcumin alleviates diabetic retinopathy in experimental diabetic rats. Ophthalmic Res 2018; 60(1): 43-54.
[] [PMID: 29597206]
Mohammad G, Siddiquei MM. Role of matrix metalloproteinase-2 and -9 in the development of diabetic retinopathy. J Ocul Biol Dis Infor 2012; 5(1): 1-8.
[] [PMID: 23833698]
Rysz J, Banach M, Stolarek RA, et al. Serum matrix metalloproteinases MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in diabetic nephropathy. J Nephrol 2007; 20(4): 444-52.
[PMID: 17879211]
Shaosheng W, Sun C, Cao H, Jiajia L, Shi X, Jun L. Effect of curcumin on expression of MMP-2 and MMP-9 in spinal dorsal horn and dorsal root ganglion of rats with type 2 diabetic neuropathic pain. Chinese J Anesthesiol 2014; 34(11): 1339-42.
Cheppudira B, Greer A, Mares A, Fowler M, Garza T, Petz L, et al. The anti-inflammatory and analgesic activity of curcumin in a rat model of full thickness thermal injury. J Pain 2013; 14(4): S52.
Li C-D, Zhao J-Y, Chen J-L, et al. Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy. Endocrine 2019; 64(1): 55-66.
[] [PMID: 30830585]
Dominguez E, Rivat C, Pommier B, Mauborgne A, Pohl M. JAK/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat. J Neurochem 2008; 107(1): 50-60.
[] [PMID: 18636982]
Ji FT, Liang JJ, Liu L, Cao MH, Li F. Curcumin exerts antinociceptive effects by inhibiting the activation of astrocytes in spinal dorsal horn and the intracellular extracellular signal-regulated kinase signaling pathway in rat model of chronic constriction injury. Chin Med J (Engl) 2013; 126(6): 1125-31.
[PMID: 23506591]
Liu S, Li Q, Zhang MT, et al. Curcumin ameliorates neuropathic pain by down-regulating spinal IL-1β via suppressing astroglial NALP1 inflammasome and JAK2-STAT3 signalling. Sci Rep 2016; 6: 28956.
[] [PMID: 27381056]
Bravo L, Llorca-Torralba M, Berrocoso E, Micó JA. Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain. Front Neurosci 2019; 13: 1268.
[] [PMID: 31942167]
Zhao X, Xu Y, Zhao Q, Chen C-R, Liu A-M, Huang Z-L. 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.
[] [PMID: 21945716]
Agarwal KA, Tripathi CD, Agarwal BB, Saluja S. Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: a double-blind, randomized placebo-controlled study. Surg Endosc 2011; 25(12): 3805-10.
[] [PMID: 21671126]
Zhu Q, Sun Y, Yun X, Ou Y, Zhang W, Li JX. Antinociceptive effects of curcumin in a rat model of postoperative pain. Sci Rep 2014; 4: 4932.
[] [PMID: 24816565]
Zhao X, Wang C, Zhang JF, et al. Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor. Psychopharmacology (Berl) 2014; 231(10): 2171-87.
[] [PMID: 24297305]
Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010; 50: 295-322.
[] [PMID: 20055706]
Zammataro M, Sortino MA, Parenti C, Gereau RW IV, Chiechio S. HDAC and HAT inhibitors differently affect analgesia mediated by group II metabotropic glutamate receptors Mol Pain 2014.
Carrasco C, Naziroǧlu M, Rodríguez AB, Pariente JA. Neuropathic Pain: Delving into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels. Front Physiol 2018; 9: 95.
[] [PMID: 29491840]
Yang M, Wang J, Yang C, Han H, Rong W, Zhang G. Oral administration of curcumin attenuates visceral hyperalgesia through inhibiting phosphorylation of TRPV1 in rat model of ulcerative colitis. Mol Pain 2017; 13: 1744806917726416.
[] [PMID: 28812431]
Chen Y, Yang C, Wang ZJ. Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia. J Neurosci 2010; 30(1): 38-46.
[] [PMID: 20053885]
Hu X, Huang F, Szymusiak M, Tian X, Liu Y, Wang ZJ. PLGA-curcumin attenuates opioid-induced hyperalgesia and inhibits spinal CaMKIIα. PLoS One 2016; 11(1)
Seo E-J, Efferth T, Panossian A. Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells. Phytomedicine 2018; 50: 285-99.
[] [PMID: 30466988]
Qin X, Qiao H, Wu S, Cheng J, Wan Q, Liu R. Curcumin inhibits monocyte chemoattractant protein-1 expression in TNF-α induced astrocytes through AMPK pathway. Neurochem Res 2018; 43(4): 775-84.
[] [PMID: 29460119]
Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF, Nair LS. Curcumin-loaded poly(ε-caprolactone) nanofibres: diabetic wound dressing with anti-oxidant and anti-inflammatory properties. Clin Exp Pharmacol Physiol 2009; 36(12): 1149-56.
[] [PMID: 19473187]
Wang L, Li N, Lin D, Zang Y. Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway. Oncotarget 2017; 8(39): 65414-20.
[] [PMID: 29029441]
Ouyang J, Li R, Shi H, Zhong J. Curcumin Protects Human Umbilical Vein Endothelial Cells against H2O2-Induced Cell Injury. Pain Res Manage 2019.
Jacob JN, Badyal DK, Bala S, Toloue M. Evaluation of the in vivo anti-inflammatory and analgesic and in vitro anti-cancer activities of curcumin and its derivatives Nat Prod Commun 2013; 8(3)
De Paz-Campos MA, Chávez-Piña AE, Ortiz MI, Castañeda-Hernández G. Evidence for the participation of ATP-sensitive potassium channels in the antinociceptive effect of curcumin. Korean J Pain 2012; 25(4): 221-7.
[] [PMID: 23091682]
Cao H, Zheng JW, Li JJ, Meng B, Li J, Ge RS. Effects of curcumin on pain threshold and on the expression of nuclear factor κ B and CX3C receptor 1 after sciatic nerve chronic constrictive injury in rats. Chin J Integr Med 2014; 20(11): 850-6.
[] [PMID: 24474673]
Arora V, Kuhad A, Tiwari V, Chopra K. Curcumin ameliorates reserpine-induced pain-depression dyad: behavioural, biochemical, neurochemical and molecular evidences. Psychoneuroendocrinology 2011; 36(10): 1570-81.
[] [PMID: 21612876]
Sahbaie P, Sun Y, Liang DY, Shi XY, Clark JD. Curcumin treatment attenuates pain and enhances functional recovery after incision. Anesth Analg 2014; 118(6): 1336-44.
[] [PMID: 24755847]
Jiajia L, Yimei M, Lian Q, Jun L, Cao H. Effects of curcumin on activity of NR2B and NR1 in spinal dorsal horn in a rat model of diabetic neuropathic pain. Chinese J Anesthesiol 2014; 34(8): 972-5.
López-Jornet P, Camacho-Alonso F, Jiménez-Torres MJ, Orduña-Domingo A, Gómez-García F. Topical curcumin for the healing of carbon dioxide laser skin wounds in mice. Photomed Laser Surg 2011; 29(12): 809-14.
[] [PMID: 21819258]
Nonose N, Pereira JA, Machado PRM, Rodrigues MR, Sato DT, Martinez CAR. Oral administration of curcumin (Curcuma longa) can attenuate the neutrophil inflammatory response in zymosan-induced arthritis in rats. Acta Cir Bras 2014; 29(11): 727-34.
[] [PMID: 25424293]
Ceyhan D, Kocman AE, Yildirim E, Ozatik O, Aydin S, Kose A. Comparison of the Effects of Curcumin, Tramadol and Surgical Treatments on Neuropathic Pain Induced by Chronic Constriction Injury in Rats. Turk Neurosurg 2018; 28(2): 288-95.
[PMID: 28481389]
Yu W, Wu J, Cai F, et al. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS One 2012; 7(12): e52013.
[] [PMID: 23251674]
El Nebrisi EG, Bagdas D, Toma W, et al. Curcumin acts as a positive allosteric modulator of α7-nicotinic acetylcholine receptors and reverses nociception in mouse models of inflammatory pain. J Pharmacol Exp Ther 2018; 365(1): 190-200.
[] [PMID: 29339457]
Yu X. Curcumin attenuates the expression of NMDAR-NR1 in Chronic Constructive Injury model of neuropathic pain. Int J Pharmacol Res 2015; 5(2): 35.
Cao H, Yu X, Li J, Lian Q. Curcumin attenuates mechanical and thermal hyperalgesia in CCI Model of neuropathic pain. Pain Ther 2014; 3(1): 59-69.
[] [PMID: 25135388]
Zhang L, Ding X, Xue F. Metabonomics analysis on biomarkers in depression induced by neuropathic pain and therapeutic effect of Curcumin American Society of Anesthesiologists Annual Meeting Scientific Abstracts A2296.
Lee JY, Shin TJ, Choi JM, et al. Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice. Br J Anaesth 2013; 111(4): 667-72.
[] [PMID: 23719767]
Tamadonfard E, Hamzeh Goshchi F, Hamzeh Gooshchi N. Effect of curcumin on morphine-induced antinociception in acute corneal pain in rats Iranian J Veterin Med 2010; 4(2)
Dang J, Wang X, Zhou L, Cao H, Yan W, Jun L, et al. Effects of curcumin on type 2 diabetic neuropathic pain and expression of inositol-requiring enzyme 1α in spinal dorsal horn and dorsal root ganglia in rats. Chinese J Anesthesiol 2012; 32(6): 676-9.
Xiangdi Y, Cao H. Effect of curcumin on the 11β-hydroxysteroid dehyarogenase 1 expression in spinal cords neuropathic pain rat model J Int Pharm Res 2017; 44(6): 551-.
Nurullahoglu KE, Okudan N, Belviranli M, Oz M. The comparison of preemptive analgesic effects of curcumin and diclofenac. Bratisl Lek Listy 2014; 115(12): 757-60.
[] [PMID: 25520223]
Yang J-H, Zhang R, Li H, Xiu B-H, Yan Z-Q, LIU S-m. Effect of Curcumin on hyperalgesia of diabetic rats. Prog Mod Biomed 2011; 13.
Ling-Li H, Xu L, Hong C. Effects of curcumin on the neuropathic pain in rats with ligation of sciatic nerve. J Herald Med 2009; p. 4.
Wu Y, Yu C-C, Cao H, Dang J-K, Lian Q-Q, Li J. Effect of endoplasmic reticulum stress protein BiP on type 2 diabetic neuropathic pain in rats treated with curcumin. In: Chinese J Pathophysiol. 2012; p. 10.
Han YK, Lee SH, Jeong HJ, Kim MS, Yoon MH, Kim WM. Analgesic effects of intrathecal curcumin in the rat formalin test. Korean J Pain 2012; 25(1): 1-6.
[] [PMID: 22259709]
Fattori V, Pinho-Ribeiro FA, Borghi SM, et al. Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation. Inflamm Res 2015; 64(12): 993-1003.
[] [PMID: 26456836]
Park S-H, Sim Y-B, Kim S-M, Kang Y-J, Lee J-K, Suh H-W. Antinociceptive profiles and mechanisms of orally administered curcumin in various pain models. J Korean Soc Appl Biol Chem 2012; 55(1): 57-61.
Di YX, Hong C, Jun L, Renshan G, Qinquan L. Curcumin attenuates mechanical and thermal hyperalgesia in chronic constrictive injury model of neuropathic pain. Pain Ther 2014; 3(1): 59-69.
[] [PMID: 25135388]
Kaur M, Singh A, Kumar B, et al. Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats. Eur J Pharmacol 2017; 805: 58-66.
[] [PMID: 28315678]

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