Abstract
Curcumin (Curcuma longa, [1E,6E]-1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive action. In this study, the analgesic efficacy of intravenous curcumin for inflammatory pain was investigated using adult male Sprague-Dawley rats weighing between 200 and 300 g. Curcumin (1, 2.5, 5, and 10 mg/kg) and normal saline solution (0.2 mL) or DMSO (1 %, 0.2 mL) were intravascularly administered, respectively, to each group of five rats 30 s before the formalin test was performed, where phase I and II data were collected. Immunohistochemical analysis was performed to assess the localization of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the L4–L6 spinal cord of three rats from each of 1 mg/kg, 10 mg/kg and the control (DMSO, 1 %, 0.2 mL) group. It was found that the number of flinching responses were significantly decreased for 1 mg/kg and 10 mg/kg groups in phase I (p < 0.05) compared to the control group. However, there were no significant differences between the curcumin and control groups in phase II. In this phase, appearance of the peak point shifted to the right in the curcumin groups. The sum of the numbers of the responses from phase I and II did not appear to be significantly decreased by the amount of curcumin. As the peak point of the Time Effect Curve for phase I progressed over time over phase II, the mean plaque shifted to the right. The peak at 30 min was significantly delayed more than 10 min in 5 and 10 mg/kg groups compared to the controls. Immunohistochemistry results do not seem to be significantly different in each group except in IL-1β in curcumin 10 mg/kg group.
Similar content being viewed by others
References
Vogel, H.A., Pelletier, J.: Curcumin-biological and medicinal properties. J. Pharmacol. 2, 50–50 (1815)
Miłobedzka, J., Kostanecki, S., Lampe, V.: Zur Kenntnis des Curcumins. Ber. Dtsch. Chem. Ges. 43, 2163–2170 (1910)
Nelson, K.M., Dahlin, J.L., Bisson, J., Graham, J., Pauli, G.F., Walters, M.A.: The essential medicinal chemistry of curcumin. J. Med. Chem. 60, 1620–1637 (2017)
US National Center for Complementary and Integrative Health, National Institutes of Health: Turmeric. May 31, 2016 (https://nccih.nih.gov/health/turmeric/ataglance.htm)
Martins, C.V.B., da Silva, D.L., Neres, A.T.M., Magalhães, T.F.F., Watanabe, G.A., Modolo, L.V., Sabino, A.A., de Fátima, Â, de Resende, M.A.: Curcumin as a promising antifungal of clinical interest. J. Antimicrob. Chemother. 63, 337–339 (2009)
Aplsarlyakul, A., Vanittanakom, N., Buddhasukh, D.: Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae). J. Ethnopharmacol. 49, 163–119 (1995)
Aggarwal, B.B., Kumar, A., Bharti, A.C.: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 23, 363–398 (2003)
Shishodia, S., Sethi, G., Aggarwal, B.B.: Curcumin: Getting Back to the Roots. Ann. N.Y. Acad. Sci. 1056, 206–217 (2005)
Agrawal, D.K., Mishra, P.K.: Curcumin and its analogues: Potential anticancer agents. Med. Res. Rev. 30, 810–860 (2010)
Chen, J., He, Z.-M., Wang, F.-L., Zhang, Z.-S., Liu, X.-Z., Zhai, D.-D., Chen, W.-D.: Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections. Eur. J. Pharmacol. 772, 33–42 (2016)
Vallianou, N.G., Evangelopoulos, A., Schizas, N., Kazazis, C.: Potential Anticancer Properties and Mechanisms of Action of Curcumin. Anticancer Res. 35, 645–651 (2015)
Hamaguchi, T., Ono, K., Yamada, M.: Curcumin and Alzheimer’s Disease. CNS Neurosci. Ther. 16, 285–297 (2010)
Ringman, J.M., Frautschy, S.A., Cole, G.M., Masterman, D.L., Cummings, J.L.: A Potential Role of the Curry Spice Curcumin in Alzheimer’s Disease. Curr. Alzheimer Res. 2, 131–136 (2005)
Mishra, S., Palanivelu, K.: The effect of curcumin (turmeric) on Alzheimer’s disease: An overview. Ann. Indian Acad. Neurol. 11, 13–19 (2008)
Ringman, J.M., Frautschy, S.A., Teng, E., Begum, A.N., Bardens, J., Beigi, M., Gylys, K.H., Badmaev, V., Heath, D.D., Apostolova, L.G., Porter, V., Vanek, Z., Marshall, G.A., Hellemann, G., Sugar, C., Masterman, D.L., Montine, T.J., Cummings, J.L., Cole, G.M.: Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimer’s Res. Ther. 4, 43 (2012)
Motterlini, R., Foresti, R., Bassi, R., Green, C.J.: Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic. Biol. Med. 28, 1303–1312 (2000)
Priyadarsini, K.I., Maity, D.K., Naik, G.H., Kumar, M.S., Unnikrishnan, M.K., Satav, J.G., Mohan, H.: Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radic. Biol. Med. 35, 475–484 (2003)
Kuo, M.L., Huang, T.S., Lin, J.K.: Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. Biochim. Biophys. Acta 1317, 95–100 (1996)
Khalil, O.A.K., de Faria Oliveira, O.M.M., Vellosa, J.C.R., de Quadros, A.U., Dalposso, L.M., Karam, T.K., Mainardes, R.M., Khalil, N.M.: Curcumin antifungal and antioxidant activities are increased in the presence of ascorbic acid. Food Chem. 133, 1001–1005 (2012)
Jurenka, J.S.: Anti-inflammatory properties of curcumin, a major constituent of curcuma longa: a review of preclinical and clinical research. Altern. Med. Rev. 14, 141–153 (2009)
Chainani-Wu, N.: Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa). J. Altern. Complement. Med. 9, 161–168 (2003)
Srimal, R.C., Dhawan, B.N.: Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J. Pharm. Pharmacol. 25, 447–452 (1973)
Rajakrishnan, V., Viswanathan, P., Rajasekharan, K.N., Menon, V.P.: Neuroprotective role of curcumin from Curcuma longa on ethanol-induced brain damage. Phytother. Res. 13, 71–574 (1999)
Aggarwal, B.B., Surh, Y.J., Shishodia, S. (eds.): The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Springer, New York (2007)
Thiyagarajan, M., Sharma, S.S.: Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci. 74, 969–985 (2004)
Mythri, R.B., Srinivas Bharath, M.M.: Curcumin: a potential neuroprotective agent in Parkinson’s disease. Curr. Pharm. Des. 18, 91–99 (2012)
Mathew, D., Hsu, W.L.: Antiviral potential of curcumin. J. Funct. Foods. 40, 692–699 (2018)
Norris, L., Karmokar, A., Howells, L., Steward, W.P., Gescher, A., Brown, K.: The role of cancer stem cells in the anti-carcinogenicity of curcumin. Mol. Nutr. Food Res. 57, 1630–1637 (2013)
Qadir, M.I., Naqvi, S.T.Q., Muhammad, S.A.: Curcumin: a polyphenol with molecular targets for cancer control. Asian Pac. J. Cancer Prev. 17, 2735–2739 (2016)
Senft, C., Polacin, M., Priester, M., Seifert, V., Kögel, D., Weissenberger, J.: The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas. BMC Cancer 10, 491 (2010)
Sandur, S.K., Pandey, M.K., Sung, B., Ahn, K.S., Murakami, A., Sethi, G., Limtrakul, P., Badmaev, V., Aggarwal, B.B.: Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 28, 1765–1773 (2007)
Zhu, Q., Sun, Y., Yun, X., Ou, Y., Zhang, W., Li, J.X.: Antinociceptive effects of curcumin in a rat model of postoperative pain. Sci. Rep. 4, 4932 (2014)
Zhou, J., Qu, F., Zhang, H.J., Zhuge, X.H., Cheng, L.Z.: Comparison of anti-inflammatory and anti-nociceptive activities of Curcuma wenujin ET C. Ling and Scutellaria baicalensis Georgi. Afr. J. Tradit. Complement. Altern. Med. 7, 339–349 (2010)
Hewlings, S.J., Kalman, D.S.: Curcumin: a review of its effects on human health. Foods 6, 92 (2017)
David, D., Stephen, G.D.: The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4, 161–174 (1977)
Shibata, M., Ohkubo, T., Takahashi, H., Inoki, R.: Modified formalin test: characteristic biphasic pain response. Pain 38, 347–352 (1989)
Han, Y.K., Lee, S.H., Jeong, H.J., Kim, M.S., Yoon, M.H., Kim, W.M.: Analgesic effects of intrathecal curcumin in the rat formalin test. Korean J. Pain 25, 1–6 (2012)
Ju, J., Shin, J.Y., Yoon, J.J., Yin, M., Yoon, M.H.: Differential expression of spinal γ-aminobutyric acid and opioid receptors modulates the analgesic effects of intrathecal curcumin on postoperative/inflammatory pain in rats. Anesth. Pain Med. 13, 82–92 (2018)
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. 5, 10278 (2015)
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 62, 843–854 (2012)
Sameer, S., Srinivas, K.K., Agrewala, J.N., Chopra, K.: Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain. Eur. J. Pharmacol. 536, 256–261 (2006)
Yeon, K.Y., Kim, S.A., Kim, Y.H., Lee, M.K., Ahn, D.K., Kim, H.J., Kim, J.S., Jung, S.J., Oh, S.B.: Curcumin produces an antihyperalgesic effect via antagonism of TRPV1. J. Dent. Res. 89, 170–174 (2010)
Guimarães, M.R., Coimbra, L.S., de Aquino, S.G., Spolidorio, L.C., Kirkwood, K.L., Rossa, C., Jr.: Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. J. Periodont. Res. 46, 269–279 (2011)
Siddiqui, A.M., Cui, X., Wu, R., Dong, W., Zhou, M., Hu, M., Simms, H.H., Wang, P.: The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-γ*. Crit. Care Med. 34, 1874–1882 (2006)
Kim, G.Y., Kim, K.H., Lee, S.H., Yoon, M.S., Lee, H.J., Moon, D.O., Lee, C.M., Ahn, S.C., Park, Y.C., Park, Y.M.: Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-κB as potential targets. J. Immunol. 174, 8116–8124 (2005)
Gulcubuk, A., Altunatmaz, K., Sonmez, K., Haktanir-Yatkin, D., Uzun, H., Gurel, A., Aydin, S.: Effects of Curcumin on Tumour Necrosis Factor-α and Interleukin-6 in the Late Phase of Experimental Acute Pancreatitis. J. Vet. Med. Ser. A. 53, 49–54 (2006)
Thaloor, D., Miller, K.J., Gephart, J., Mitchell, P.O., Pavlath, G.K.: Systemic administration of the NF-κB inhibitor curcumin stimulates muscle regeneration after traumatic injury. Am. J. Physiol. Cell Physiol. 277, C320–C329 (1999)
Karin, M., Clevers, H.: Reparative inflammation takes charge of tissue regeneration. Nature 529, 307–315 (2016)
El-Morsy, H.H., Aboul-Ela, Y.M.S., Hasanin, A.H., Abd El-Aziz, L.F., Masoud, S.I., Hamza, M.: Low Concentrations of Dimethyl Sulphoxide Mask the Antinociceptive Activity of Paracetamol in the Mouse Formalin Test. Life Sci. J. 10, 1856–1861 (2013)
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ok, HG., Kim, H.W. & Kim, HK. Analgesic effects of intravenous curcumin in the rat formalin test. J Incl Phenom Macrocycl Chem 101, 337–344 (2021). https://doi.org/10.1007/s10847-021-01080-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-021-01080-8