Abstract
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition, experienced by patients undergoing chemotherapy with some specific drugs, such as platinum-based agents, taxanes, and vinca alkaloids. Painful CIPN may lead to dose interruptions and discontinuation of chemotherapy and can negatively impact on the quality of life and clinical outcome of these patients. Due to a lack of a practical medical therapy for CIPN, it is necessary to further explore and identify novel therapeutic options.
Methods: We have reviewed PubMed and EMBASE libraries to gather data on the mechanism-based pharmacological management of chemotherapy-induced neuropathic pain.
Results: This review has focused on the potential mechanisms by which these chemotherapeutic agents may be involved in the development of CIPN, and explains how this may be translated into clinical management. Additionally, we have presented an overview of emerging candidates for the prevention and treatment of CIPN in preclinical and clinical studies.
Conclusion: Taken together, due to the debilitating consequences of CIPN for the quality of life and clinical outcome of cancer survivors, future studies should focus on identifying underlying mechanisms contributing to CIPN as well as developing effective pharmacological interventions based on these mechanistic insights.
Keywords: Chemotherapy-induced peripheral neuropathy, neuropathic pain, platinum-based agents, taxanes, vinca alkaloids, chemotherapy.
[http://dx.doi.org/10.1016/j.pain.2014.09.020] [PMID: 25261162]
[http://dx.doi.org/10.1007/s00520-021-06502-4] [PMID: 34410459]
[http://dx.doi.org/10.1200/JCO.20.01399] [PMID: 32663120]
[http://dx.doi.org/10.1007/s11864-021-00926-0] [PMID: 35167004]
[http://dx.doi.org/10.1001/jama.2021.0106] [PMID: 33591350]
[http://dx.doi.org/10.1038/nrneurol.2014.211] [PMID: 25366108]
[http://dx.doi.org/10.3389/fphar.2022.750507] [PMID: 35418856]
[http://dx.doi.org/10.1007/s00415-020-09942-w] [PMID: 32474658]
[http://dx.doi.org/10.1016/j.biopha.2022.112671] [PMID: 35104697]
[http://dx.doi.org/10.3389/fmolb.2021.693133] [PMID: 34179101]
[http://dx.doi.org/10.2174/1381612828666220922111342] [PMID: 36154599]
[http://dx.doi.org/10.1016/j.ynpai.2021.100082] [PMID: 35024498]
[http://dx.doi.org/10.1016/j.neuropharm.2019.107905] [PMID: 31811874]
[http://dx.doi.org/10.1097/j.pain.0000000000001774] [PMID: 31815915]
[http://dx.doi.org/10.2174/1389200221666200711155632] [PMID: 32651960]
[http://dx.doi.org/10.1016/j.biopha.2018.07.039] [PMID: 30119265]
[http://dx.doi.org/10.1002/ptr.6159] [PMID: 30069944]
[http://dx.doi.org/10.1177/1744806917724715] [PMID: 28741430]
[http://dx.doi.org/10.1002/advs.202101717] [PMID: 34658162]
[http://dx.doi.org/10.1038/s41598-020-70691-x] [PMID: 32843690]
[http://dx.doi.org/10.3390/ijms23052692] [PMID: 35269831]
[http://dx.doi.org/10.1038/srep02005] [PMID: 23774285]
[http://dx.doi.org/10.1021/acs.jmedchem.7b01237] [PMID: 29048889]
[http://dx.doi.org/10.3389/fncel.2017.00219] [PMID: 28785206]
[http://dx.doi.org/10.1016/j.expneurol.2016.04.022] [PMID: 27132993]
[http://dx.doi.org/10.1016/j.biochi.2021.12.013] [PMID: 34979156]
[http://dx.doi.org/10.3390/md17050265]
[http://dx.doi.org/10.1021/acschemneuro.0c00476] [PMID: 33073974]
[http://dx.doi.org/10.1038/s41598-019-48231-z] [PMID: 31409858]
[http://dx.doi.org/10.1016/j.jpain.2011.11.009] [PMID: 22325298]
[http://dx.doi.org/10.1016/j.brainres.2020.147079] [PMID: 32866545]
[http://dx.doi.org/10.1007/s10753-017-0645-y] [PMID: 28812173]
[http://dx.doi.org/10.1111/jns.12307] [PMID: 30680838]
[http://dx.doi.org/10.1007/s13311-020-00873-y] [PMID: 32572830]
[http://dx.doi.org/10.1371/journal.pone.0128080] [PMID: 26039098]
[http://dx.doi.org/10.1038/srep03905] [PMID: 24469566]
[http://dx.doi.org/10.1038/srep37850] [PMID: 27910870]
[http://dx.doi.org/10.1002/ejp.550] [PMID: 25045036]
[http://dx.doi.org/10.2174/1381612828666220728152350] [PMID: 35909286]
[http://dx.doi.org/10.3390/ijms20071652] [PMID: 30987090]
[http://dx.doi.org/10.1016/j.drugalcdep.2020.107946] [PMID: 32145665]
[http://dx.doi.org/10.3390/toxins11070396] [PMID: 31288453]
[http://dx.doi.org/10.1016/j.ejmech.2021.113956] [PMID: 34731762]
[http://dx.doi.org/10.1016/j.ejmech.2021.113793] [PMID: 34507012]
[http://dx.doi.org/10.1021/acs.jmedchem.9b02135] [PMID: 32364386]
[http://dx.doi.org/10.1016/j.expneurol.2015.11.001] [PMID: 26546510]
[http://dx.doi.org/10.4103/1673-5374.235305] [PMID: 30106061]
[http://dx.doi.org/10.1016/j.bcp.2020.114255] [PMID: 33010214]
[http://dx.doi.org/10.1016/j.ejmech.2021.113650] [PMID: 34174741]
[http://dx.doi.org/10.3390/ijms23010098] [PMID: 35008525]
[http://dx.doi.org/10.1186/s40478-022-01315-w] [PMID: 35093182]
[http://dx.doi.org/10.1523/JNEUROSCI.0899-17.2017] [PMID: 29255002]
[http://dx.doi.org/10.1158/1535-7163.MCT-20-0006] [PMID: 32847971]
[http://dx.doi.org/10.1016/j.lfs.2022.120760] [PMID: 35787997]
[http://dx.doi.org/10.1002/jbt.22834] [PMID: 34056794]
[http://dx.doi.org/10.3389/fonc.2021.763229] [PMID: 35070969]
[http://dx.doi.org/10.3389/fncom.2020.564980] [PMID: 33178002]
[http://dx.doi.org/10.3389/fphar.2018.01510] [PMID: 30666203]
[http://dx.doi.org/10.1016/j.biopha.2020.110210] [PMID: 32407991]
[http://dx.doi.org/10.1007/s10787-019-00625-1] [PMID: 31388880]
[http://dx.doi.org/10.1038/aps.2016.58] [PMID: 27498772]
[http://dx.doi.org/10.1016/j.biopha.2018.09.018] [PMID: 30218861]
[http://dx.doi.org/10.1523/JNEUROSCI.1816-17.2017] [PMID: 29192128]
[http://dx.doi.org/10.1016/j.neulet.2022.136512] [PMID: 35149198]
[http://dx.doi.org/10.3390/cells10030547] [PMID: 33806325]
[http://dx.doi.org/10.1007/s00520-021-06269-8] [PMID: 34003380]
[http://dx.doi.org/10.1097/j.pain.0000000000002502] [PMID: 35001054]
[http://dx.doi.org/10.1016/j.jpain.2018.10.007] [PMID: 30414958]
[http://dx.doi.org/10.1016/j.biopha.2020.110456] [PMID: 32603895]
[http://dx.doi.org/10.1016/j.jphs.2019.02.007] [PMID: 30871874]
[http://dx.doi.org/10.1038/srep10541] [PMID: 26085115]
[http://dx.doi.org/10.1124/mol.115.098483] [PMID: 25904556]
[http://dx.doi.org/10.1016/j.biopsych.2014.04.009] [PMID: 24853387]
[http://dx.doi.org/10.1016/j.neuropharm.2017.07.015] [PMID: 28729222]
[http://dx.doi.org/10.1016/j.biopha.2020.110356] [PMID: 32535388]
[http://dx.doi.org/10.1111/jcmm.15427] [PMID: 32485058]
[PMID: 34904193]
[http://dx.doi.org/10.1016/j.ejphar.2017.11.024] [PMID: 29154935]
[http://dx.doi.org/10.1007/s13577-019-00238-4] [PMID: 30701373]
[http://dx.doi.org/10.1016/j.jpain.2018.11.003] [PMID: 30471427]
[http://dx.doi.org/10.1016/j.neuroscience.2013.09.033] [PMID: 24070631]
[http://dx.doi.org/10.1093/abbs/gmw083] [PMID: 27563006]
[http://dx.doi.org/10.1007/s12035-019-1616-0] [PMID: 31037647]
[http://dx.doi.org/10.3390/pharmaceutics14040848] [PMID: 35456682]
[http://dx.doi.org/10.1016/j.ejphar.2020.173306] [PMID: 32603693]
[http://dx.doi.org/10.1523/JNEUROSCI.1324-21.2021] [PMID: 35042769]
[http://dx.doi.org/10.1007/s13311-021-01158-8] [PMID: 34796458]
[http://dx.doi.org/10.1177/1744806918801224] [PMID: 30157705]
[http://dx.doi.org/10.1016/j.neuropharm.2020.108445] [PMID: 33383089]
[http://dx.doi.org/10.1111/jnc.13103] [PMID: 25827582]
[http://dx.doi.org/10.1186/s13041-022-00924-9] [PMID: 35526002]
[http://dx.doi.org/10.1084/jem.20201452] [PMID: 33656514]
[http://dx.doi.org/10.1016/j.neuropharm.2018.03.004] [PMID: 29518397]
[http://dx.doi.org/10.1007/s13311-019-00784-7] [PMID: 31617070]
[http://dx.doi.org/10.1016/j.intimp.2020.107060] [PMID: 33049496]
[http://dx.doi.org/10.1097/ALN.0000000000001601] [PMID: 28306698]
[http://dx.doi.org/10.1080/01480545.2019.1706547] [PMID: 31899978]
[http://dx.doi.org/10.2147/JPR.S224478] [PMID: 32104054]
[http://dx.doi.org/10.3390/toxins13040235] [PMID: 33805908]
[http://dx.doi.org/10.1016/j.thromres.2016.09.011] [PMID: 27693845]
[http://dx.doi.org/10.1161/ATVBAHA.107.150631] [PMID: 18599803]
[http://dx.doi.org/10.1007/s00280-020-04135-8] [PMID: 32965539]
[http://dx.doi.org/10.1111/j.1526-4637.2007.00325.x] [PMID: 19067834]
[http://dx.doi.org/10.1002/pbc.28539] [PMID: 32618122]
[http://dx.doi.org/10.1634/theoncologist.2017-0235] [PMID: 28652279]
[http://dx.doi.org/10.1001/jama.2013.2813] [PMID: 23549581]
[http://dx.doi.org/10.1097/MD.0000000000018653] [PMID: 31895829]
[http://dx.doi.org/10.3389/fphar.2019.00838] [PMID: 31402867]
[http://dx.doi.org/10.1089/pmr.2020.0031] [PMID: 34223452]
[http://dx.doi.org/10.1186/1744-8069-10-11] [PMID: 24517272]
[http://dx.doi.org/10.1007/s13311-017-0572-5] [PMID: 28924870]
[PMID: 36582060]
[PMID: 31093677]
[http://dx.doi.org/10.1186/s12885-021-08884-4] [PMID: 34727879]
[http://dx.doi.org/10.1007/s00520-018-4618-y] [PMID: 30607681]
[http://dx.doi.org/10.1007/s00520-010-0911-0] [PMID: 20496177]
[http://dx.doi.org/10.1007/s12032-017-1015-1] [PMID: 28819738]
[http://dx.doi.org/10.3390/antiox8120588] [PMID: 31779159]
[http://dx.doi.org/10.1097/j.pain.0000000000001924] [PMID: 32433266]
[http://dx.doi.org/10.1038/s41598-017-08891-1] [PMID: 28851920]
[http://dx.doi.org/10.1016/j.ejphar.2017.12.036] [PMID: 29262297]
[http://dx.doi.org/10.1016/j.ejphar.2016.04.033] [PMID: 27089821]
[http://dx.doi.org/10.1002/ardp.202000225] [PMID: 32939789]
[http://dx.doi.org/10.1016/j.neuropharm.2017.04.029] [PMID: 28431970]
[http://dx.doi.org/10.1097/WNR.0000000000000516] [PMID: 26730517]
[http://dx.doi.org/10.1097/CAD.0000000000000949] [PMID: 32459682]
[http://dx.doi.org/10.3389/fphar.2021.774795] [PMID: 35153744]
[http://dx.doi.org/10.1016/j.pbb.2014.03.025] [PMID: 24726707]
[http://dx.doi.org/10.1016/j.neuropharm.2018.07.026] [PMID: 30056126]
[http://dx.doi.org/10.1016/j.jphs.2018.10.006] [PMID: 30409714]
[http://dx.doi.org/10.3390/molecules26123577] [PMID: 34208184]
[http://dx.doi.org/10.1097/j.pain.0000000000001448] [PMID: 30507781]
[http://dx.doi.org/10.1248/bpb.b19-00862] [PMID: 31776306]
[http://dx.doi.org/10.1016/j.bmc.2015.02.027] [PMID: 25766630]
[http://dx.doi.org/10.1016/j.expneurol.2018.09.014] [PMID: 30253135]
[http://dx.doi.org/10.1124/jpet.112.197665] [PMID: 22988061]
[http://dx.doi.org/10.1016/j.npep.2016.12.007] [PMID: 28041630]
[http://dx.doi.org/10.1016/j.ejphar.2015.10.005] [PMID: 26450087]
[http://dx.doi.org/10.1021/acs.jmedchem.7b00383] [PMID: 28525717]
[http://dx.doi.org/10.1016/j.lfs.2013.12.229] [PMID: 24412642]
[http://dx.doi.org/10.1007/s11064-013-1103-3] [PMID: 23836292]
[http://dx.doi.org/10.1002/ejp.1097] [PMID: 28877402]
[http://dx.doi.org/10.4196/kjpp.2021.25.5.489] [PMID: 34448466]
[http://dx.doi.org/10.1016/j.ejphar.2020.173196] [PMID: 32416186]
[http://dx.doi.org/10.1371/journal.pone.0054161] [PMID: 23326593]
[http://dx.doi.org/10.1016/j.neuroscience.2011.05.004] [PMID: 21596106]
[http://dx.doi.org/10.1097/FBP.0000000000000497] [PMID: 31503072]
[http://dx.doi.org/10.1124/jpet.117.245704] [PMID: 29540562]
[http://dx.doi.org/10.3390/biomedicines9040346] [PMID: 33808052]
[PMID: 27228525]
[http://dx.doi.org/10.3389/fphar.2016.00532] [PMID: 28138318]
[http://dx.doi.org/10.18632/oncotarget.25524] [PMID: 29963257]
[http://dx.doi.org/10.3389/fphar.2017.00885] [PMID: 29255417]
[http://dx.doi.org/10.1213/ANE.0000000000000853] [PMID: 26214551]
[http://dx.doi.org/10.1016/j.neuint.2018.08.007] [PMID: 30118739]
[http://dx.doi.org/10.18632/oncotarget.15533] [PMID: 28423567]
[http://dx.doi.org/10.3390/md18010012] [PMID: 31877728]
[http://dx.doi.org/10.1016/j.expneurol.2015.09.006] [PMID: 26376216]
[http://dx.doi.org/10.2220/biomedres.34.105] [PMID: 23594484]
[http://dx.doi.org/10.1016/j.biopha.2021.112331] [PMID: 34673421]
[http://dx.doi.org/10.1016/j.phrs.2019.02.002] [PMID: 30739035]
[http://dx.doi.org/10.1016/j.pain.2009.09.006] [PMID: 19833436]
[http://dx.doi.org/10.1016/j.phymed.2016.12.010] [PMID: 28190463]
[http://dx.doi.org/10.1016/j.neulet.2020.135471] [PMID: 33207243]
[http://dx.doi.org/10.1007/s13311-021-01069-8] [PMID: 34312766]
[http://dx.doi.org/10.1007/s13311-021-01093-8] [PMID: 34291431]
[http://dx.doi.org/10.3389/fphar.2021.744663] [PMID: 34975470]
[http://dx.doi.org/10.3390/ijms22116084] [PMID: 34199936]
[http://dx.doi.org/10.1111/bcpt.13454] [PMID: 32542990]
[http://dx.doi.org/10.1007/s10571-019-00679-3] [PMID: 31011938]
[http://dx.doi.org/10.1016/j.fct.2012.01.038] [PMID: 22326968]
[http://dx.doi.org/10.1080/01480545.2018.1547739] [PMID: 30554535]
[http://dx.doi.org/10.1007/s11064-016-2040-8] [PMID: 27561290]
[http://dx.doi.org/10.1007/s10072-013-1603-6] [PMID: 24337989]
[http://dx.doi.org/10.4097/kja.19481] [PMID: 32046474]
[http://dx.doi.org/10.1016/j.biopha.2020.110003] [PMID: 32187955]
[http://dx.doi.org/10.1007/s00210-017-1426-8] [PMID: 28916845]
[PMID: 28535568]
[http://dx.doi.org/10.3389/fnins.2019.00653] [PMID: 31316337]
[http://dx.doi.org/10.1016/j.ejphar.2008.10.004] [PMID: 18938155]
[http://dx.doi.org/10.1111/j.1529-8027.2012.00413.x] [PMID: 22971094]
[http://dx.doi.org/10.3892/mmr.2016.6071] [PMID: 28035379]
[http://dx.doi.org/10.1002/cncr.23008] [PMID: 17853395]
[http://dx.doi.org/10.1002/cncr.23482] [PMID: 18428211]
[http://dx.doi.org/10.1007/s00520-010-1018-3] [PMID: 20936417]
[http://dx.doi.org/10.1111/ajco.12822] [PMID: 29280313]
[http://dx.doi.org/10.1007/s00520-016-3404-y] [PMID: 27612466]
[http://dx.doi.org/10.1007/s10549-020-05762-8] [PMID: 32601973]
[http://dx.doi.org/10.1200/JCO.2012.44.8738] [PMID: 23733756]
[http://dx.doi.org/10.1016/j.ejca.2005.04.028] [PMID: 16039110]