BISDEMETHOXYCURCUMIN ATTENUATES SCIATIC NERVE INJURY IN VINCRISTINE- INDUCED NEUROPATHIC PAIN MICE

Chalton Manengu

Abstract


Chemotherapy-induced neuropathic pain is a common side effect for cancer patients. There are many therapeutic choices available today, but they typically have negative side effects and are ineffective at reducing pain. As a result, novel strategies for treating chemotherapy induced neuropathic pain are being investigated, particularly those involving natural substances. Bisdemethoxycurcumin (BDCM), a component of turmeric, is a potential target. This study explores the potential of BDCM in lessening pain sensitivity and restoring sciatic nerve damage. Mice were injected with vincristine sulfate intraperitoneally to create the study model. The cold plate test, thermal radiation test, and Von Frey test were used to evaluate the potential pain-relieving benefits of BDCM. We employed transmission electron microscopy (TEM), hematoxylin and eosin staining, silver staining, and an electrophysiological stimulation test to assess BDCM's possible neuroprotective effect on the sciatic nerve. We further evaluated BDCM’s effects on NF-κB and pro-inflammatory cytokines. BDCM treatment reduced the frequency of paw lifts, increased the latency before paw withdrawal, and significantly raised the paw withdrawal threshold. BDCM reduced sciatic nerve tissue damage and increased sensory nerve conduction velocity. Additionally, BDCM decreased NF-κB and pro-inflammatory cytokines expression. These findings demonstrate that BDCM alleviates VCR-induced sciatic nerve damage and preserves nerve integrity, highlighting its potential as a novel therapeutic agent for neuropathic pain and further studies should further explore its mechanisms in neuropathic pain attenuation.

Keywords


bisdemethoxycurcumin; vincristine; chemotherapy; neuropathic pain; antinociception; neuroprotection

Full Text:

PDF

References


D’Souza RS, Alvarez GAM, Dombovy-Johnson M, Eller J, Abd-Elsayed A. Evidence-Based Treatment of Pain in Chemotherapy-Induced Peripheral Neuropathy. Current pain and headache reports. 2023;27(5):99-116. https://doi.org/10.1007/s11916-023-01107-4

Sisignano M, Baron R, Scholich K, Geisslinger G. Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain. Nature Reviews Neurology. 2014;10(12):694-707. https://doi.org/10.1038/nrneurol.2014.211

Zhang S. Chemotherapy-induced peripheral neuropathy and rehabilitation: A review. Seminars in oncology. 2021;48(3):193-207. https://doi.org/10.1053/j.seminoncol.2021.09.004

Bae EH, Greenwald MK, Schwartz AG. Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Therapeutic Avenues. Neurotherapeutics: the journal of the American Society for Experimental Neuro Therapeutics. 2021;18(4):2384-96. https://doi.org/10.1007/s13311-021-01142-2

Bennett GJ, Doyle T, Salvemini D. Mitotoxicity in distal symmetrical sensory peripheral neuropathies. Nature Reviews Neurology. 2014;10(6):326-36. https://doi.org/10.1038/nrneurol.2014.77

Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal transduction and targeted therapy. 2017;2:17023. https://doi.org/10.1038/sigtrans.2017.23

Singh S, Singh TG. Role of Nuclear Factor Kappa B (NF-κB) Signalling in Neurodegenerative Diseases: A Mechanistic Approach. Current neuropharmacology. 2020;18(10):918-35. https://doi.org/10.2174/1570159x18666200207120949

Guo HM, Zhang Y, Zhang Y, Jiao PF, Fan XC, Kong CL, et al. Spinal Ninjurin2 contributes to the neuropathic pain via NF-κB-mediated neuroinflammation in the spared sciatic nerve injury rats. International immunopharmacology. 2021;99:107918. https://doi.org/10.1016/j.intimp.2021.107918

Lee KM, Kang BS, Lee HL, Son SJ, Hwang SH, Kim DS, et al. Spinal NF-kB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity. The European journal of neuroscience. 2004;19(12):3375-81. https://doi.org/10.1111/j.0953-816X.2004.03441.x

Ahmed AS, Berg S, Alkass K, Druid H, Hart DA, Svensson CI, et al. NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease. International journal of molecular sciences. 2019;20(3). https://doi.org/10.3390/ijms20030658

Kunnumakkara AB, Shabnam B, Girisa S, Harsha C, Banik K, Devi TB, et al. Inflammation, NF-κB, and Chronic Diseases: How are They Linked? Critical reviews in immunology. 2020;40(1):1-39. https://doi.org/10.1615/CritRevImmunol.2020033210

Roberti A, Chaffey LE, Greaves DR. NF-κB Signaling and Inflammation-Drug Repurposing to Treat Inflammatory Disorders? Biology. 2022;11(3). https://doi.org/10.3390/biology11030372

Huang C, Lu HF, Chen YH, Chen JC, Chou WH, Huang HC. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and -independent apoptosis via Smad or Akt signaling pathways in HOS cells. BMC complementary medicine and therapies. 2020;20(1):68. https://doi.org/10.1186/s12906-020-2857-1

Wang Q, Liu J, Liu J, Thant YM, Weng W, Wei C, et al. Bisdemethoxycurcumin-conjugated vitamin E TPGS liposomes ameliorate poor bioavailability of free form and evaluation of its analgesic and hypouricemic activity in oxonate-treated rats. 2021;23.

Jin G, Xu W, Tang H, Cui Y, Zhang H. Bisdemethoxycurcumin, a curcumin, protects chondrocytes, and reduces cartilage inflammation via the NRF2/HO-1/NLRP3 pathway. Immunity, inflammation and disease.2024;12(2):e1195. https://doi.org/10.1002/iid3.1195

Sun X, Liang Y, Wang Y, Sun C, Wang X. Bisdemethoxycurcumin, a curcumin derivative, ameliorates adjuvant-induced arthritis by suppressing inflammatory reactions and macrophage migration. Chemico-biological interactions. 2024;387:110822. https://doi.org/10.1016/j.cbi.2023.110822

Guo, Cai XF, Lee JJ, Kang SS, Shin EM, Zhou HY, et al. Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin on expressions of inflammatory mediators in vitro and in vivo. Archives of pharmacal research. 2008;31(4):490-6. https://doi.org/10.1007/s12272-001-1183-8

Authier N, Gillet JP, Fialip J, Eschalier A, Coudore F. A new animal model of vincristine-induced nociceptive peripheral neuropathy. Neurotoxicology. 2003;24(6):797-805. https://doi.org/10.1016/s0161-813x(03)00043-3

Sweitzer SM, Pahl JL, DeLeo JA. Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat. Neuroscience letters. 2006;400(3):258-61. https://doi.org/10.1016/j.neulet.2006.02.058

Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. Journal of neuroscience methods. 1994;53(1):55-63. https://doi.org/10.1016/0165-0270(94)90144-9

Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32(1):77-88. https://doi.org/10.1016/0304-3959(88)90026-7

Cheah M, Fawcett JW, Andrews MR. Assessment of Thermal Pain Sensation in Rats and Mice Using the Hargreaves Test. Bio-protocol. 2017;7(16). https://doi.org/10.21769/BioProtoc.2506

Jasmin L, Kohan L, Franssen M, Janni G, Goff JR. The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models. Pain. 1998;75(2-3):367-82. https://doi.org/10.1016/s0304-3959(98)00017-7

Chiechio S, Copani A, Gereau RWt, Nicoletti F. Acetyl-L-carnitine in neuropathic pain: experimental data. CNS drugs. 2007;21 Suppl 1:31-8; discussion 45-6. https://doi.org/10.2165/00023210-200721001-00005

Gabay E, Tal M. Pain behavior and nerve electrophysiology in the CCI model of neuropathic pain. Pain. 2004;110(1-2):354-60. https://doi.org/10.1016/j.pain.2004.04.021

Sudoh Y, Desai S, Haderer AE, Sudoh S, Gerner P, Anthony DC, et al. Neurologic and histopathologic evaluation after high-volume intrathecal amitriptyline. 2004;29:434 - 40.

Zhang., Liu N, Zhu C, Ma L, Yang J, Du J, et al. Antinociceptive effect of isoorientin against neuropathic pain induced by the chronic constriction injury of the sciatic nerve in mice. International immunopharmacology. 2019;75:105753. https://doi.org/10.1016/j.intimp.2019.105753

Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: A current review. Annals of neurology. 2017;81(6):772-81. https://doi.org/10.1002/ana.24951

Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain. 2014;155(12):2461-70. https://doi.org/10.1016/j.pain.2014.09.020

Araújo CC, Leon LL. Biological activities of Curcuma longa L. Memorias do Instituto Oswaldo Cruz. 2001;96(5):723-8. https://doi.org/10.1590/s0074-02762001000500026

Wakte PS, Sachin BS, Patil AA, Mohato DM, Band TH, Shinde DJS, et al. Optimization of microwave, ultra-sonic and supercritical carbon dioxide assisted extraction techniques for curcumin from Curcuma longa. 2011;79:50-5.

Kaltschmidt C, Greiner JFW, Kaltschmidt B. The Transcription Factor NF-κB in Stem Cells and Development. Cells. 2021;10(8). https://doi.org/10.3390/cells10082042

Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harbor perspectives in biology. 2009;1(4):a000034. https://doi.org/10.1101/cshperspect.a000034

Yin Q, Fan Q, Zhao Y, Cheng MY, Liu H, Li J, et al. Spinal NF-κB and chemokine ligand 5 expression during spinal glial cell activation in a neuropathic pain model. PLoS One. 2015;10(1):e0115120. https://doi.org/10.1371/journal.pone.0115120




DOI: http://dx.doi.org/10.46827/ejphs.v9i2.274

Refbacks

  • There are currently no refbacks.


Copyright (c) 2026 Chalton Manengu

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2019 - 2026. European Journal of Public Health Studies (ISSN 2668-1056/ISSN-L 2668-1056) is a registered trademark of Open Access Publishing Group. All rights reserved.

This journal is a serial publication uniquely identified by an International Standard Serial Number (ISSN) serial number certificate issued by Romanian National Library. All the research works are uniquely identified by a CrossRef DOI digital object identifier supplied by indexing and repository platforms. All the research works published on this journal are meeting the Open Access Publishing requirements and standards formulated by Budapest Open Access Initiative (2002), the Bethesda Statement on Open Access Publishing (2003) and Berlin Declaration on Open Access to Knowledge in the Sciences and Humanities (2003) and can be freely accessed, shared, modified, distributed and used in educational, commercial and non-commercial purposes under a Creative Commons Attribution 4.0 International License. Copyrights of the published research works are retained by authors.