The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain

Overview

Journal Medicina (Kaunas)

Publisher MDPI

Specialty General Medicine

Date 2024 Mar 28

PMID 38541085

Authors

Hiroshi Yokomi

Takahiro Kato

Soshi Narasaki

Satoshi Kamiya

Shima Taguchi

Yosuke T Horikawa

Yasuo M Tsutsumi

Affiliations

Soon will be listed here.

Abstract

Refractory peripheral neuropathy can occur as a side effect in 60-70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT] receptor antagonist) and Ketanserin (5-HT receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.

Citing Articles

Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Diabetes-Induced Neuropathic Pain.

Kajikawa Y, Yokomi H, Narasaki S, Kamiya S, Miyoshi H, Kato T J Clin Med. 2024; 13(14).

PMID: 39064315 PMC: 11277645. DOI: 10.3390/jcm13144276.

Phytoconstituents Targeting the Serotonin 5-HT Receptor: Promising Therapeutic Strategies for Neurological Disorders.

Akotkar L, Aswar U, Ganeshpurkar A, Rathod K, Bagad P, Gurav S ACS Pharmacol Transl Sci. 2024; 7(6):1694-1710.

PMID: 38898946 PMC: 11184608. DOI: 10.1021/acsptsci.4c00084.

References

Sinha R . P-CPA pretreatment reverses the changes in sleep and behavior following acute immobilization stress rats. J Physiol Sci. 2006; 56(1):123-9. DOI: 10.2170/physiolsci.r2127. View

Kawada K, Ishida T, Jobu K, Morisawa S, Kawazoe T, Nishida M . Yokukansan suppresses neuroinflammation in the hippocampus of mice and decreases the duration of lipopolysaccharide- and diazepam-mediated loss of righting reflex induced by pentobarbital. J Nat Med. 2022; 76(3):634-644. DOI: 10.1007/s11418-022-01612-7. View

Thangamani D, Edafiogho I, Masocha W . The anticonvulsant enaminone E139 attenuates paclitaxel-induced neuropathic pain in rodents. ScientificWorldJournal. 2014; 2013:240508. PMC: 3872104. DOI: 10.1155/2013/240508. View

Yamaguchi K, Yamazaki S, Kumakura S, Someya A, Iseki M, Inada E . Yokukansan, a Japanese Herbal Medicine, Suppresses Substance PInduced Production of Interleukin-6 and Interleukin-8 by Human U373 MG Glioblastoma Astrocytoma Cells. Endocr Metab Immune Disord Drug Targets. 2020; 20(7):1073-1080. DOI: 10.2174/1871530320666200131103733. View

Sunagawa M, Takayama Y, Kato M, Tanaka M, Fukuoka S, Okumo T . Kampo Formulae for the Treatment of Neuropathic Pain ∼ Especially the Mechanism of Action of ∼. Front Mol Neurosci. 2021; 14:705023. PMC: 8712661. DOI: 10.3389/fnmol.2021.705023. View

Xu Y, Jiang Z, Chen X . Mechanisms underlying paclitaxel-induced neuropathic pain: Channels, inflammation and immune regulations. Eur J Pharmacol. 2022; 933:175288. DOI: 10.1016/j.ejphar.2022.175288. View

Nishi A, Yamaguchi T, Sekiguchi K, Imamura S, Tabuchi M, Kanno H . Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin ₁A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan. Neuroscience. 2012; 207:124-36. DOI: 10.1016/j.neuroscience.2012.01.037. View

Ueki T, Mizoguchi K, Yamaguchi T, Nishi A, Ikarashi Y, Hattori T . Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice. Evid Based Complement Alternat Med. 2015; 2015:726471. PMC: 4670863. DOI: 10.1155/2015/726471. View

Yamaguchi T, Tsujimatsu A, Kumamoto H, Izumi T, Ohmura Y, Yoshida T . Anxiolytic effects of yokukansan, a traditional Japanese medicine, via serotonin 5-HT1A receptors on anxiety-related behaviors in rats experienced aversive stress. J Ethnopharmacol. 2012; 143(2):533-9. DOI: 10.1016/j.jep.2012.07.007. View

10.

Tsuda M, Inoue K, Salter M . Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia. Trends Neurosci. 2005; 28(2):101-7. DOI: 10.1016/j.tins.2004.12.002. View

11.

Pottorf T, Rotterman T, McCallum W, Haley-Johnson Z, Alvarez F . The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury. Cells. 2022; 11(13). PMC: 9265514. DOI: 10.3390/cells11132083. View

12.

Romero-Sandoval A, Eisenach J . Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision. Anesthesiology. 2007; 106(4):787-94. DOI: 10.1097/01.anes.0000264765.33673.6c. View

13.

Zhao Y, Xu J, Yi H, Baba S, Guo Y, Hou X . Activation of 5-HT receptor in the ventrolateral orbital cortex produces antinociceptive effects in rat models of neuropathic and inflammatory pain. Neuropharmacology. 2023; 245:109830. DOI: 10.1016/j.neuropharm.2023.109830. View

14.

Imamura S, Tabuchi M, Oizumi H, Ueki T, Omiya Y, Ikarashi Y . Yokukansankachimpihange, a traditional Japanese (Kampo) medicine, enhances the adaptation to circadian rhythm disruption by increasing endogenous melatonin levels. J Pharmacol Sci. 2020; 144(3):129-138. DOI: 10.1016/j.jphs.2020.08.001. View

15.

Furuya M, Miyaoka T, Tsumori T, Liaury K, Hashioka S, Wake R . Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat. J Neuroinflammation. 2013; 10:145. PMC: 4234324. DOI: 10.1186/1742-2094-10-145. View

16.

Chen N, Ge M, Li D, Wang X, Liu D, Ye D . β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis. Biomed Pharmacother. 2021; 144:112331. DOI: 10.1016/j.biopha.2021.112331. View

17.

Kawakami Z, Ikarashi Y, Kase Y . Glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid in glycyrrhiza, a constituent herb of yokukansan, ameliorate thiamine deficiency-induced dysfunction of glutamate transport in cultured rat cortical astrocytes. Eur J Pharmacol. 2009; 626(2-3):154-8. DOI: 10.1016/j.ejphar.2009.09.046. View

18.

Egashira N, Iwasaki K, Ishibashi A, Hayakawa K, Okuno R, Abe M . Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32(6):1516-20. DOI: 10.1016/j.pnpbp.2008.05.010. View

19.

Staff N, Grisold A, Grisold W, Windebank A . Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol. 2017; 81(6):772-781. PMC: 5656281. DOI: 10.1002/ana.24951. View

20.

Weaver B . How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014; 25(18):2677-81. PMC: 4161504. DOI: 10.1091/mbc.E14-04-0916. View