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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Mini-Review Article

Potential Roles of 5-HT3 Receptor Antagonists in Reducing Chemotherapy-induced Peripheral Neuropathy (CIPN)

Author(s): Raajeswari Satiamurthy, Nor Syafinaz Yaakob*, Noraida Mohamed Shah, Norazrina Azmi and Marhanis Salihah Omar

Volume 23, Issue 4, 2023

Published on: 15 July, 2022

Page: [341 - 349] Pages: 9

DOI: 10.2174/1566524022666220512122525

Price: $65

Abstract

5-HT3 receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in chemotherapy patients. However, current and previous studies reveal novel potentials of those ligands in other diseases involving the nervous system, such as addiction, pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and cognitive function. This review gathers existing studies to support the role of 5-HT3 receptors in CIPN modulation. It has been reported that chemotherapy drugs increase the 5-HT content that binds with the 5-HT3 receptor, which later induces pain. As also shown in pre-clinical and clinical studies that various neuropathic pains could be blocked by the 5-HT3 receptor antagonists, we proposed that 5-HT3 receptor antagonists via 5- HT3 receptors may also inhibit neuropathic pain induced by chemotherapy. Our review suggests that future studies focus more on the 5-HT3 receptor antagonists and their modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related pain.

Keywords: 5-HT3 receptor, cancer, chemotherapy-induced peripheral neuropathy (CIPN), neuropathic pain, cancer pain, CINV.

[1]
Davies PA, Pistis M, Hanna MC, et al. The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 1999; 397(6717): 359-63.
[http://dx.doi.org/10.1038/16941] [PMID: 9950429]
[2]
Machu TK. Therapeutics of 5-HT3 receptor antagonists: Current uses and future directions. Pharmacol Ther 2011; 130(3): 338-47.
[http://dx.doi.org/10.1016/j.pharmthera.2011.02.003] [PMID: 21356241]
[3]
Navari R. The current status of the use of palonosetron. Expert Opin Pharmacother 2013; 14(10): 1281-4.
[http://dx.doi.org/10.1517/14656566.2013.799141] [PMID: 23647207]
[4]
Kopp VJ, Shafer A. Anesthesiologists and perioperative communication. Anesthesiology 2000; 93(2): 548-55.
[http://dx.doi.org/10.1097/00000542-200008000-00035] [PMID: 10910506]
[5]
Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 2000; 118(5): 842-8.
[http://dx.doi.org/10.1016/S0016-5085(00)70170-3] [PMID: 10784583]
[6]
Delvaux M, Louvel D, Mamet J-P, Campos-Oriola R, Frexinos J. Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther 1998; 12(9): 849-55.
[http://dx.doi.org/10.1046/j.1365-2036.1998.00375.x] [PMID: 9768527]
[7]
Thompson AJ, Lummis SC. The 5-HT3 receptor as a therapeutic target. Expert Opin Ther Targets 2007; 11(4): 527-40.
[http://dx.doi.org/10.1517/14728222.11.4.527] [PMID: 17373882]
[8]
Yoon SY, Oh J. Neuropathic cancer pain: Prevalence, pathophysiology, and management. Korean J Intern Med (Korean Assoc Intern Med) 2018; 33(6): 1058-69.
[http://dx.doi.org/10.3904/kjim.2018.162] [PMID: 29929349]
[9]
Sałat K. Chemotherapy-induced peripheral neuropathy: Part 1-current state of knowledge and perspectives for pharmacotherapy. Pharmacol Rep 2020; 72(3): 486-507.
[http://dx.doi.org/10.1007/s43440-020-00109-y] [PMID: 32394362]
[10]
Miltenburg NC, Boogerd W. Chemotherapy-induced neuropathy: A comprehensive survey. Cancer Treat Rev 2014; 40(7): 872-82.
[http://dx.doi.org/10.1016/j.ctrv.2014.04.004] [PMID: 24830939]
[11]
Li Y, Lustberg MB, Hu S. Emerging pharmacological and non-pharmacological therapeutics for prevention and treatment of chemotherapy-induced peripheral neuropathy. Cancers (Basel) 2021; 13(4): 766.
[http://dx.doi.org/10.3390/cancers13040766] [PMID: 33673136]
[12]
Beijers AJM, Jongen JLM, Vreugdenhil G. Chemotherapyinduced neurotoxicity: The value of neuroprotective strategies. 2012; 70(1): 8.
[13]
Ma J, Kavelaars A, Dougherty PM, Heijnen CJ. Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source. Cancer 2018; 124(11): 2289-98.
[http://dx.doi.org/10.1002/cncr.31248] [PMID: 29461625]
[14]
Silva M, Costa-Pereira JT, Martins D, Tavares I. Pain modulation from the brain during diabetic neuropathy: Uncovering the role of the rostroventromedial medulla. Neurobiol Dis 2016; 96: 346-56.
[http://dx.doi.org/10.1016/j.nbd.2016.10.002] [PMID: 27717882]
[15]
Chen Y, Oatway MA, Weaver LC. Blockade of the 5-HT3 receptor for days causes sustained relief from mechanical allodynia following spinal cord injury. J Neurosci Res 2009; 87(2): 418-24.
[http://dx.doi.org/10.1002/jnr.21860] [PMID: 18798253]
[16]
Close LN, Cetas JS, Heinricher MM, Selden NR. Purinergic receptor immunoreactivity in the rostral ventromedial medulla. Neuroscience 2009; 158(2): 915-21.
[http://dx.doi.org/10.1016/j.neuroscience.2008.08.044] [PMID: 18805466]
[17]
Treede R-D. The international association for the study of pain definition of pain: As valid in 2018 as in 1979, but in need of regularly updated footnotes. PR9 2018; 3(2): e643.
[18]
Finnerup NB, Haroutounian S, Kamerman P, et al. Neuropathic pain: An updated grading system for research and clinical practice. Pain 2016; 157(8): 1599-606.
[http://dx.doi.org/10.1097/j.pain.0000000000000492] [PMID: 27115670]
[19]
Torta R, Ieraci V, Zizzi F. A review of the emotional aspects of neuropathic pain: From comorbidity to co-pathogenesis. Pain Ther 2017; 6 (Suppl. 1): 11-7.
[http://dx.doi.org/10.1007/s40122-017-0088-z] [PMID: 29178035]
[20]
Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers 2017; 3(1): 17002.
[http://dx.doi.org/10.1038/nrdp.2017.2] [PMID: 28205574]
[21]
Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kaasa S. Prevalence and aetiology of neuropathic pain in cancer patients: A systematic review. Pain 2012; 153(2): 359-65.
[http://dx.doi.org/10.1016/j.pain.2011.10.028] [PMID: 22115921]
[22]
Bennett MI, Kaasa S, Barke A, Korwisi B, Rief W, Treede RD. The IASP classification of chronic pain for ICD-11: Chronic cancer-related pain. Pain 2019; 160(1): 38-44.
[http://dx.doi.org/10.1097/j.pain.0000000000001363] [PMID: 30586069]
[23]
Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol 2017; 81(6): 772-81.
[http://dx.doi.org/10.1002/ana.24951] [PMID: 28486769]
[24]
Quintão NLM, Santin JR, Stoeberl LC, Corrêa TP, Melato J, Costa R. Pharmacological treatment of chemotherapy-induced neuropathic pain: PPARγ agonists as a promising tool. Front Neurosci 2019; 13: 907.
[http://dx.doi.org/10.3389/fnins.2019.00907] [PMID: 31555078]
[25]
Fallon MT. Neuropathic pain in cancer. Br J Anaesth 2013; 111(1): 105-11.
[http://dx.doi.org/10.1093/bja/aet208] [PMID: 23794652]
[26]
Boyette-Davis JA, Hou S, Abdi S, Dougherty PM. An updated understanding of the mechanisms involved in chemotherapy-induced neuropathy. Pain Manag 2018; 8(5): 363-75.
[PMID: 30212277]
[27]
Banach M, Juranek JK, Zygulska AL. Chemotherapy-induced neuropathies-a growing problem for patients and health care providers. Brain Behav 2016; 7(1)e00558
[http://dx.doi.org/10.1002/brb3.558] [PMID: 28127506]
[28]
Cavaletti G, Alberti P, Argyriou AA, Lustberg M, Staff NP, Tamburin S. Chemotherapy-induced peripheral neurotoxicity: A multifaceted, still unsolved issue. J Peripher Nerv Syst 2019; 24 (Suppl. 2): S6-S12.
[http://dx.doi.org/10.1111/jns.12337] [PMID: 31647155]
[29]
Flatters SJL, Dougherty PM, Colvin LA. Clinical and preclinical perspectives on chemotherapy-induced peripheral neuropathy (CIPN): A narrative review. Br J Anaesth 2017; 119(4): 737-49.
[http://dx.doi.org/10.1093/bja/aex229] [PMID: 29121279]
[30]
Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-induced peripheral neurotoxicity: A critical analysis. CA Cancer J Clin 2013; 63(6): 419-37.
[http://dx.doi.org/10.3322/caac.21204] [PMID: 24590861]
[31]
Bernhardson B-M, Tishelman C, Rutqvist LE. Chemosensory changes experienced by patients undergoing cancer chemotherapy: A qualitative interview study. J Pain Symptom Manage 2007; 34(4): 403-12.
[http://dx.doi.org/10.1016/j.jpainsymman.2006.12.010] [PMID: 17616338]
[32]
Kwon JH. Overcoming barriers in cancer pain management. JCO 2014; 32(16): 1727-33.
[http://dx.doi.org/10.1200/JCO.2013.52.4827]
[33]
Chan H-K, Ismail S. Side effects of chemotherapy among cancer patients in a Malaysian general hospital: Experiences, perceptions and informational needs from clinical pharmacists. Asian Pac J Cancer Prev 2014; 15(13): 5305-9.
[http://dx.doi.org/10.7314/APJCP.2014.15.13.5305] [PMID: 25040993]
[34]
Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin 2011; 61(3): 157-82.
[http://dx.doi.org/10.3322/caac.20112] [PMID: 21543825]
[35]
Khan MIA, Walsh D, Brito-Dellan N. Opioid and adjuvant analgesics: Compared and contrasted. Am J Hosp Palliat Care 2011; 28(5): 378-83.
[http://dx.doi.org/10.1177/1049909111410298] [PMID: 21622486]
[36]
Mejin M, Keowmani T, Rahman SA, et al. Prevalence of pain and treatment outcomes among cancer patients in a Malaysian palliative care unit. Pharm Pract (Granada) 2019; 17(1): 1397.
[http://dx.doi.org/10.18549/PharmPract.2019.1.1397] [PMID: 31015879]
[37]
Sisignano M, Baron R, Scholich K, Geisslinger G. Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain. Nat Rev Neurol 2014; 10(12): 694-707.
[http://dx.doi.org/10.1038/nrneurol.2014.211] [PMID: 25366108]
[38]
Bradley PB, Engel G, Feniuk W, et al. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 1986; 25(6): 563-76.
[http://dx.doi.org/10.1016/0028-3908(86)90207-8] [PMID: 2875415]
[39]
Yaakob N. Heterogeneity amongst 5-HT3 receptor subunits: Is this significant? Curr Mol Med 2011; 11(1): 57-68.
[PMID: 21189117]
[40]
Yang J. Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells. J Gen Physiol 1990; 96(6): 1177-98.
[http://dx.doi.org/10.1085/jgp.96.6.1177] [PMID: 2286832]
[41]
Jackson MB, Yakel JL. The 5-HT3 receptor channel. Annu Rev Physiol 1995; 57: 447-68.
[PMID: 7539990]
[42]
Zeitz KP, Guy N, Malmberg AB, et al. The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci 2002; 22(3): 1010-9.
[http://dx.doi.org/10.1523/JNEUROSCI.22-03-01010.2002] [PMID: 11826129]
[43]
Cortes-Altamirano JL, Olmos-Hernandez A, Jaime HB, et al. Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors and their role in the modulation of pain response in the central nervous system. Curr Neuropharmacol 2018; 16(2): 210-21.
[PMID: 28901281]
[44]
Lyubashina OA, Sivachenko IB. The 5-HT4 receptor-mediated inhibition of visceral nociceptive neurons in the rat caudal ventrolateral medulla. Neuroscience 2017; 359: 277-88.
[http://dx.doi.org/10.1016/j.neuroscience.2017.07.039] [PMID: 28754313]
[45]
Eisenberg P, MacKintosh FR, Ritch P, Cornett PA, Macciocchi A. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: A dose-ranging clinical study. Ann Oncol 2004; 15(2): 330-7.
[http://dx.doi.org/10.1093/annonc/mdh047] [PMID: 14760130]
[46]
Suzuki R, Dickenson A. Spinal and supraspinal contributions to central sensitization in peripheral neuropathy. Neurosignals 2005; 14(4): 175-81.
[http://dx.doi.org/10.1159/000087656] [PMID: 16215300]
[47]
Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullary descending facilitation. Trends Neurosci 2002; 25(6): 319-25.
[http://dx.doi.org/10.1016/S0166-2236(02)02157-4] [PMID: 12086751]
[48]
Millan MJ. Descending control of pain. Prog Neurobiol 2002; 66(6): 355-474.
[http://dx.doi.org/10.1016/S0301-0082(02)00009-6] [PMID: 12034378]
[49]
Wei F, Dubner R, Zou S, et al. Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain. J Neurosci 2010; 30(25): 8624-36.
[http://dx.doi.org/10.1523/JNEUROSCI.5389-09.2010] [PMID: 20573908]
[50]
Bardin L. The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol 2011; 22(5 and 6): 390-404.
[PMID: 21808193]
[51]
Conte D, Legg ED, McCourt AC, Silajdzic E, Nagy GG, Maxwell DJ. Transmitter content, origins and connections of axons in the spinal cord that possess the serotonin (5-hydroxytryptamine) 3 receptor. Neuroscience 2005; 134(1): 165-73.
[http://dx.doi.org/10.1016/j.neuroscience.2005.02.013] [PMID: 15975728]
[52]
Glaum SR, Brooks PA, Spyer KM, Miller RJ. 5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro. Brain Res 1992; 589(1): 62-8.
[http://dx.doi.org/10.1016/0006-8993(92)91162-8] [PMID: 1422823]
[53]
Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 1991; 254(5030): 432-7.
[http://dx.doi.org/10.1126/science.1718042] [PMID: 1718042]
[54]
Moore KA, Oh EJ, Weinreich D. 5-HT(3) receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro. J Appl Physiol 2002; 92(6): 2529-34.
[http://dx.doi.org/10.1152/japplphysiol.00974.2001] [PMID: 12015369]
[55]
Eglen RM, Lee C-H, Smith WL, et al. Pharmacological characterization of RS 25259-197, a novel and selective 5-HT3 receptor antagonist, in vivo. Br J Pharmacol 1995; 114(4): 860-6.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb13283.x] [PMID: 7773547]
[56]
Liu X, Wang G, Ai G, et al. Selective ablation of descending serotonin from the rostral ventromedial medulla unmasks its pro-nociceptive role in chemotherapy-induced painful neuropathy. JPR 2020; 13: 3081-94.
[http://dx.doi.org/10.2147/JPR.S275254]
[57]
Rojas C, Thomas AG, Alt J, et al. Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol 2010; 626(2-3): 193-9.
[http://dx.doi.org/10.1016/j.ejphar.2009.10.002] [PMID: 19836386]
[58]
McCleane G, Suzuki R, Dickenson A. The 5HT3 receptor antagonist ondansetron can have an analgesic effect in chronic human neuropathic pain: Two case reports. J Neuropathic Pain Symptom Palliation 2005; 1(1): 77-9.
[http://dx.doi.org/10.3109/J426v01n01_12]
[59]
Misra A, Sangraula H, Rauniar GP, et al. Ondansetron versus amitriptyline in the treatment of peripheral neuropathy: A randomized double blind prospective clinical study. Br J Med Med Res 2014; 4(26): 4444-54.
[http://dx.doi.org/10.9734/BJMMR/2014/11176]
[60]
Ray S. Effects of granisetron on experimental model of diabetes induced neuropathic pain perception. Int J Pharm Pharm Sci 2014; 6(1): 483-6.
[http://dx.doi.org/10.3390/ijms20061451]
[61]
Suzuki R, Rahman W, Hunt SP, Dickenson AH. Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res 2004; 1019(1-2): 68-76.
[http://dx.doi.org/10.1016/j.brainres.2004.05.108] [PMID: 15306240]
[62]
Nasirinezhad F, Hosseini M, Karami Z, Yousefifard M, Janzadeh A. Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron. J Spinal Cord Med 2016; 39(2): 212-9.
[http://dx.doi.org/10.1179/2045772315Y.0000000047] [PMID: 26338446]
[63]
Hagiwara H, Sunada Y. Mechanism of taxane neurotoxicity. Breast Cancer 2004; 11(1): 82-5.
[http://dx.doi.org/10.1007/BF02968008] [PMID: 14718798]
[64]
Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol 2010; 6(12): 657-66.
[http://dx.doi.org/10.1038/nrneurol.2010.160] [PMID: 21060341]
[65]
Samineni VK, Premkumar LS, Faingold CL. Neuropathic pain-induced enhancement of spontaneous and pain-evoked neuronal activity in the periaqueductal gray that is attenuated by gabapentin. Pain 2017; 158(7): 1241-53.
[http://dx.doi.org/10.1097/j.pain.0000000000000905] [PMID: 28328571]
[66]
Costa-Pereira JT, Serrão P, Martins I, Tavares I. Serotoninergic pain modulation from the rostral ventromedial medulla (RVM) in chemotherapy-induced neuropathy: The role of spinal 5-HT3 receptors. Eur J Neurosci 2020; 51(8): 1756-69.
[http://dx.doi.org/10.1111/ejn.14614] [PMID: 31691396]
[67]
Lim B-S, Moon HJ, Li DX, et al. Effect of bee venom acupuncture on oxaliplatin-induced cold allodynia in Rats 2013. Evid Based Complement Altern Med 2013; p. 369324.
[http://dx.doi.org/10.1155/2013/369324]
[68]
Lee JH, Kim W. Involvement of serotonergic system in oxaliplatin-induced neuropathic pain. Biomedicines 2021; 9(8): 970.
[http://dx.doi.org/10.3390/biomedicines9080970] [PMID: 34440174]

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