Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications

Overview

Journal Front Neurosci

Date 2020 Jun 27

PMID 32587501

Citations 18

Authors

Md Sahab Uddin

Abdullah Al Mamun

Md Ataur Rahman

Md Tanvir Kabir

Saad Alkahtani

Ibtesam S Alanazi

Asma Perveen

Ghulam Md Ashraf

May N Bin-Jumah

Mohamed M Abdel-Daim

Affiliations

Soon will be listed here.

Abstract

Neuropathic pain (NP) is the result of irregular processing in the central or peripheral nervous system, which is generally caused by neuronal injury. The management of NP represents a great challenge owing to its heterogeneous profile and the significant undesirable side effects of the frequently prescribed psychoactive agents, including benzodiazepines (BDZ). Currently, several established drugs including antidepressants, anticonvulsants, topical lidocaine, and opioids are used to treat NP, but they exert a wide range of adverse effects. To reduce the burden of adverse effects, we need to investigate alternative therapeutics for the management of NP. Flavonoids are the most common secondary metabolites of plants used in folkloric medicine as tranquilizers, and have been claimed to have a selective affinity to the BDZ binding site. Several studies in animal models have reported that flavonoids can reduce NP. In this paper, we emphasize the potentiality of flavonoids for the management of NP.

Citing Articles

Endoplasmic reticulum stress in diseases.

Liu Y, Xu C, Gu R, Han R, Li Z, Xu X MedComm (2020). 2024; 5(9):e701.

PMID: 39188936 PMC: 11345536. DOI: 10.1002/mco2.701.

Attenuation of Streptozotocin-Induced Diabetic Neuropathic Allodynia by Flavone Derivative Through Modulation of GABA-ergic Mechanisms and Endogenous Biomarkers.

Altaf N, Ur Rehman N, Karim N, Khan I, Ahsan Halim S, Alotaibi B Neurochem Res. 2024; 49(4):980-997.

PMID: 38170385 DOI: 10.1007/s11064-023-04078-5.

The Multimodal Properties of Quercetin in Chronic Pain Syndromes.

Nair A Indian J Palliat Care. 2023; 29(3):334-335.

PMID: 37700889 PMC: 10493683. DOI: 10.25259/IJPC_151_2022.

Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents.

Santonocito S, Donzella M, Venezia P, Nicolosi G, Mauceri R, Isola G Pharmaceutics. 2023; 15(4).

PMID: 37111679 PMC: 10142272. DOI: 10.3390/pharmaceutics15041193.

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics.

Alini M, Diwan A, Erwin W, Little C, Melrose J JOR Spine. 2023; 6(1):e1230.

PMID: 36994457 PMC: 10041392. DOI: 10.1002/jsp2.1230.

References

Borghi S, Mizokami S, Pinho-Ribeiro F, Fattori V, Crespigio J, Clemente-Napimoga J . The flavonoid quercetin inhibits titanium dioxide (TiO)-induced chronic arthritis in mice. J Nutr Biochem. 2017; 53:81-95. DOI: 10.1016/j.jnutbio.2017.10.010. View

Wang Y, Chen P, Tang C, Wang Y, Li Y, Zhang H . Antinociceptive and anti-inflammatory activities of extract and two isolated flavonoids of Carthamus tinctorius L. J Ethnopharmacol. 2013; 151(2):944-50. DOI: 10.1016/j.jep.2013.12.003. View

Stein A, Arnold D . Oxaliplatin: a review of approved uses. Expert Opin Pharmacother. 2011; 13(1):125-37. DOI: 10.1517/14656566.2012.643870. View

Ferrandiz M, Alcaraz M . Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Actions. 1991; 32(3-4):283-8. DOI: 10.1007/BF01980887. View

Eaton M, Martinez M, Karmally S . A single intrathecal injection of GABA permanently reverses neuropathic pain after nerve injury. Brain Res. 1999; 835(2):334-9. DOI: 10.1016/s0006-8993(99)01564-4. View

Semyanov A, Walker M, Kullmann D . GABA uptake regulates cortical excitability via cell type-specific tonic inhibition. Nat Neurosci. 2003; 6(5):484-90. DOI: 10.1038/nn1043. View

Sommer C, Kress M . Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004; 361(1-3):184-7. DOI: 10.1016/j.neulet.2003.12.007. View

Anjaneyulu M, Chopra K . Quercetin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats. Indian J Exp Biol. 2004; 42(8):766-9. View

Ossipov M, Dussor G, Porreca F . Central modulation of pain. J Clin Invest. 2010; 120(11):3779-87. PMC: 2964993. DOI: 10.1172/JCI43766. View

10.

Zeilhofer H . Loss of glycinergic and GABAergic inhibition in chronic pain--contributions of inflammation and microglia. Int Immunopharmacol. 2008; 8(2):182-7. DOI: 10.1016/j.intimp.2007.07.009. View

11.

Gilron I, Watson C, Cahill C, Moulin D . Neuropathic pain: a practical guide for the clinician. CMAJ. 2006; 175(3):265-75. PMC: 1513412. DOI: 10.1503/cmaj.060146. View

12.

Ma W, Eisenach J . Cyclooxygenase 2 in infiltrating inflammatory cells in injured nerve is universally up-regulated following various types of peripheral nerve injury. Neuroscience. 2003; 121(3):691-704. DOI: 10.1016/s0306-4522(03)00495-0. View

13.

Lindenlaub T, Sommer C . Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. Acta Neuropathol. 2003; 105(6):593-602. DOI: 10.1007/s00401-003-0689-y. View

14.

Stavniichuk R, Drel V, Shevalye H, Maksimchyk Y, Kuchmerovska T, Nadler J . Baicalein alleviates diabetic peripheral neuropathy through inhibition of oxidative-nitrosative stress and p38 MAPK activation. Exp Neurol. 2011; 230(1):106-13. PMC: 4215942. DOI: 10.1016/j.expneurol.2011.04.002. View

15.

Ferrandiz M, Gil B, Sanz M, Ubeda A, Erazo S, Gonzalez E . Effect of bakuchiol on leukocyte functions and some inflammatory responses in mice. J Pharm Pharmacol. 1996; 48(9):975-80. DOI: 10.1111/j.2042-7158.1996.tb06016.x. View

16.

Uddin M, Kabir M, Jakaria M, Al Mamun A, Niaz K, Amran M . Endothelial PPARγ Is Crucial for Averting Age-Related Vascular Dysfunction by Stalling Oxidative Stress and ROCK. Neurotox Res. 2019; 36(3):583-601. DOI: 10.1007/s12640-019-00047-5. View

17.

Wolfman C, Viola H, Marder M, Ardenghi P, Wasowski C, Schroder N . Pharmacological characterization of 6-bromo-3'-nitroflavone, a synthetic flavonoid with high affinity for the benzodiazepine receptors. Pharmacol Biochem Behav. 1998; 61(3):239-46. DOI: 10.1016/s0091-3057(98)00088-4. View

18.

Xifro X, Vidal-Sancho L, Boadas-Vaello P, Turrado C, Alberch J, Puig T . Novel epigallocatechin-3-gallate (EGCG) derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice. PLoS One. 2015; 10(4):e0123122. PMC: 4391943. DOI: 10.1371/journal.pone.0123122. View

19.

Komirishetty P, Areti A, Sistla R, Kumar A . Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation. Neurochem Res. 2016; 41(8):2029-42. DOI: 10.1007/s11064-016-1914-0. View

20.

Muto N, Matsuoka Y, Arakawa K, Kurita M, Omiya H, Taniguchi A . Quercetin Attenuates Neuropathic Pain in Rats with Spared Nerve Injury. Acta Med Okayama. 2018; 72(5):457-465. DOI: 10.18926/AMO/56243. View