Skip to main content

Advertisement

SpringerLink
Log in

Analgesic effects of intravenous curcumin in the rat formalin test

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Vogel, H.A., Pelletier, J.: Curcumin-biological and medicinal properties. J. Pharmacol. 2, 50–50 (1815)

    Google Scholar 

  2. Miłobedzka, J., Kostanecki, S., Lampe, V.: Zur Kenntnis des Curcumins. Ber. Dtsch. Chem. Ges. 43, 2163–2170 (1910)

    Article  Google Scholar 

  3. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. US National Center for Complementary and Integrative Health, National Institutes of Health: Turmeric. May 31, 2016 (https://nccih.nih.gov/health/turmeric/ataglance.htm)

  5. 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)

    Article  CAS  PubMed  Google Scholar 

  6. Aplsarlyakul, A., Vanittanakom, N., Buddhasukh, D.: Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae). J. Ethnopharmacol. 49, 163–119 (1995)

    Article  Google Scholar 

  7. Aggarwal, B.B., Kumar, A., Bharti, A.C.: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 23, 363–398 (2003)

    CAS  PubMed  Google Scholar 

  8. Shishodia, S., Sethi, G., Aggarwal, B.B.: Curcumin: Getting Back to the Roots. Ann. N.Y. Acad. Sci. 1056, 206–217 (2005)

    Article  CAS  PubMed  Google Scholar 

  9. Agrawal, D.K., Mishra, P.K.: Curcumin and its analogues: Potential anticancer agents. Med. Res. Rev. 30, 810–860 (2010)

    Google Scholar 

  10. 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)

    Article  CAS  PubMed  Google Scholar 

  11. Vallianou, N.G., Evangelopoulos, A., Schizas, N., Kazazis, C.: Potential Anticancer Properties and Mechanisms of Action of Curcumin. Anticancer Res. 35, 645–651 (2015)

    CAS  PubMed  Google Scholar 

  12. Hamaguchi, T., Ono, K., Yamada, M.: Curcumin and Alzheimer’s Disease. CNS Neurosci. Ther. 16, 285–297 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mishra, S., Palanivelu, K.: The effect of curcumin (turmeric) on Alzheimer’s disease: An overview. Ann. Indian Acad. Neurol. 11, 13–19 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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)

    Article  CAS  Google Scholar 

  16. 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)

    Article  CAS  PubMed  Google Scholar 

  17. 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)

    Article  CAS  PubMed  Google Scholar 

  18. 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)

    Article  CAS  PubMed  Google Scholar 

  19. 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)

    Article  CAS  Google Scholar 

  20. 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)

    PubMed  Google Scholar 

  21. Chainani-Wu, N.: Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa). J. Altern. Complement. Med. 9, 161–168 (2003)

    Article  PubMed  Google Scholar 

  22. Srimal, R.C., Dhawan, B.N.: Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J. Pharm. Pharmacol. 25, 447–452 (1973)

    Article  CAS  PubMed  Google Scholar 

  23. 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)

    Article  Google Scholar 

  24. 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)

  25. 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)

    Article  CAS  PubMed  Google Scholar 

  26. Mythri, R.B., Srinivas Bharath, M.M.: Curcumin: a potential neuroprotective agent in Parkinson’s disease. Curr. Pharm. Des. 18, 91–99 (2012)

    Article  CAS  PubMed  Google Scholar 

  27. Mathew, D., Hsu, W.L.: Antiviral potential of curcumin. J. Funct. Foods. 40, 692–699 (2018)

    Article  CAS  Google Scholar 

  28. 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)

    Article  CAS  PubMed  Google Scholar 

  29. 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)

    PubMed  Google Scholar 

  30. 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)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. 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)

    Article  CAS  PubMed  Google Scholar 

  32. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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)

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hewlings, S.J., Kalman, D.S.: Curcumin: a review of its effects on human health. Foods 6, 92 (2017)

    Article  PubMed Central  CAS  Google Scholar 

  35. 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)

    Article  Google Scholar 

  36. Shibata, M., Ohkubo, T., Takahashi, H., Inoki, R.: Modified formalin test: characteristic biphasic pain response. Pain 38, 347–352 (1989)

    Article  PubMed  Google Scholar 

  37. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 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)

    Article  Google Scholar 

  39. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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)

    Article  CAS  PubMed  Google Scholar 

  41. 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)

    Article  CAS  Google Scholar 

  42. 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)

    Article  CAS  PubMed  Google Scholar 

  43. 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)

    Article  CAS  Google Scholar 

  44. 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)

    Article  CAS  PubMed  Google Scholar 

  45. 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)

    Article  CAS  PubMed  Google Scholar 

  46. 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)

    Article  CAS  Google Scholar 

  47. 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)

    Article  CAS  Google Scholar 

  48. Karin, M., Clevers, H.: Reparative inflammation takes charge of tissue regeneration. Nature 529, 307–315 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 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)

    Google Scholar 

Download references

Author information

Author notes

  1. Dedicated to the memory of Jacques Vicens.

Authors and Affiliations

  1. Department of Medicine, The Graduate School, Pusan National University, 179, Gudeok-ro, Seo-gu, 49241, Busan, South Korea

    Hwoe-Gyeong Ok & Hae-Kyu Kim

  2. Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, 49241, Busan, South Korea

    Hyeon Woo Kim

Authors
  1. Hwoe-Gyeong Ok
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyeon Woo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hae-Kyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hae-Kyu Kim.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-021-01080-8

Keywords

Search

Navigation