Abstract
Natural products and leads inspired by them have acted as a probe for successful drug discovery for many decades. Pain is an obnoxious sensory and emotional experience associated with potential tissue damage. It affects the quality of life of patients to a greater extent. Despite the availability of several agents targeting TRP receptors, none of them can proficiently alleviate neuropathic pain. TRPV1 is a prospective target for treating neuropathic pain as it is recognized to modulate the pain circuitry at the periphery and the central level. In this review, we have discussed several natural molecules, such as Capsaicinoids, Capsinoids, Piperine, Eugenol, Scutigeral, Ginsenosides, Cinnamaldehyde, Camphor, Shogaol, Gingerols, Zingerone, Allicin, Evodiamine, Allylisothiocyanate, Cannabidiol, Ricinoleic acid, Isovelleral, Capsazepine, Thapsigargin, Pellitorine, Yohimbine, Curcumin and some semi-synthetic analogues that activate TRPV1 channels and consequently, can be further harnessed for the treatment of neuropathic pain.
Keywords: TRPV1 channels, neuropathic pain, natural products, semi-synthetic analogues, agonists, antagonists.
Graphical Abstract
[http://dx.doi.org/10.1097/j.pain.0000000000001824] [PMID: 33090746]
[http://dx.doi.org/10.1016/j.pain.2013.11.013] [PMID: 24291734]
[http://dx.doi.org/10.1093/pm/pnab050] [PMID: 33561282]
[http://dx.doi.org/10.1039/C9NP00056A] [PMID: 32065187]
[http://dx.doi.org/10.1155/2021/8894752] [PMID: 33552153]
[http://dx.doi.org/10.1016/j.pharmthera.2020.107686] [PMID: 32961262]
[http://dx.doi.org/10.1021/acs.jnatprod.9b01285] [PMID: 32162523]
[http://dx.doi.org/10.1021/acs.jnatprod.9b01285.]
[http://dx.doi.org/10.1038/nrdp.2017.2] [PMID: 28205574]
[http://dx.doi.org/10.7861/clinmed.2020-1009] [PMID: 33479064]
[http://dx.doi.org/10.2174/1389201020666191202111534] [PMID: 31793418]
[http://dx.doi.org/10.1038/ncpneuro0113] [PMID: 16932531]
[http://dx.doi.org/10.1007/s40122-017-0087-0] [PMID: 29178033]
[http://dx.doi.org/10.1111/jop.13071] [PMID: 32531812]
[http://dx.doi.org/10.1097/j.pain.0000000000000492] [PMID: 27115670]
[http://dx.doi.org/10.1038/39807] [PMID: 9349813]
[http://dx.doi.org/10.1124/pr.112.006163] [PMID: 23023032]
[http://dx.doi.org/10.1146/annurev-pharmtox-010617-052832] [PMID: 28945977]
[http://dx.doi.org/10.1080/13543776.2020.1797679] [PMID: 32686526]
[PMID: 33377418]
[http://dx.doi.org/10.1155/2020/3764193] [PMID: 32273889]
[http://dx.doi.org/10.3390/cells9122604] [PMID: 33291725]
[http://dx.doi.org/10.3389/fcell.2020.584206] [PMID: 33363143]
[http://dx.doi.org/10.1016/j.coph.2016.10.002] [PMID: 27835802]
[http://dx.doi.org/10.1074/jbc.RA120.015605] [PMID: 33060203]
[http://dx.doi.org/10.3390/cells9061341] [PMID: 32471282]
[http://dx.doi.org/10.1016/j.bbrc.2021.03.126] [PMID: 33839411]
[http://dx.doi.org/10.1016/j.tins.2020.03.004] [PMID: 32353335]
[http://dx.doi.org/10.1002/bab.2086] [PMID: 33316085]
[http://dx.doi.org/10.1016/j.mcn.2015.02.001] [PMID: 25662734]
[http://dx.doi.org/10.7150/ijms.4706] [PMID: 23091405]
[http://dx.doi.org/10.1016/j.neuron.2013.12.011] [PMID: 24462040]
[http://dx.doi.org/10.1073/pnas.0610811104] [PMID: 17551020]
[http://dx.doi.org/10.1038/ncomms15292] [PMID: 28489079]
[http://dx.doi.org/10.1523/JNEUROSCI.23-10-04017.2003] [PMID: 12764087]
[http://dx.doi.org/10.1186/1742-2094-9-16] [PMID: 22264228]
[http://dx.doi.org/10.1016/j.expneurol.2009.09.030] [PMID: 19815011]
[http://dx.doi.org/10.1038/aps.2016.58] [PMID: 27498772]
[http://dx.doi.org/10.1038/sj.bjp.0707411] [PMID: 17700720]
[http://dx.doi.org/10.1124/jpet.110.178491] [PMID: 21343315]
[http://dx.doi.org/10.1016/j.bmc.2008.11.085] [PMID: 19135377]
[http://dx.doi.org/10.3389/fphys.2014.00171] [PMID: 24847275]
[http://dx.doi.org/10.1016/j.neuroscience.2015.02.041] [PMID: 25743251]
[http://dx.doi.org/10.1016/j.jep.2010.08.034] [PMID: 20728519]
[http://dx.doi.org/10.1016/j.ejphar.2010.09.074] [PMID: 20946891]
[http://dx.doi.org/10.1016/j.ejphar.2020.173356] [PMID: 32763303]
[http://dx.doi.org/10.1186/s12870-015-0476-7] [PMID: 25884984]
[http://dx.doi.org/10.1021/jf403553w] [PMID: 24147886]
[http://dx.doi.org/10.1080/10408398.2013.772090] [PMID: 25675368]
[http://dx.doi.org/10.1016/bs.apcsb.2015.11.005] [PMID: 27038373]
[http://dx.doi.org/10.1007/s11745-008-3182-5] [PMID: 18481133]
[http://dx.doi.org/10.1186/s12967-019-02200-2] [PMID: 31952468]
[http://dx.doi.org/10.1038/nchembio.1835] [PMID: 26053297]
[http://dx.doi.org/10.1007/s13238-016-0353-7] [PMID: 28044278]
[http://dx.doi.org/10.1117/1.JBO.22.7.076010] [PMID: 28715544]
[http://dx.doi.org/10.1517/14656566.2010.481670] [PMID: 20446852]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3756] [PMID: 21487045]
[http://dx.doi.org/10.1016/j.pnpbp.2003.10.007] [PMID: 14751425]
[http://dx.doi.org/10.1080/09168451.2016.1254533] [PMID: 27838955]
[http://dx.doi.org/10.1016/j.drudis.2018.06.020] [PMID: 29969684]
[http://dx.doi.org/10.3390/molecules21080966] [PMID: 27455231]
[http://dx.doi.org/10.1124/jpet.104.074864] [PMID: 15356216]
[http://dx.doi.org/10.1016/S0024-3205(96)00567-X] [PMID: 9064473]
[http://dx.doi.org/10.2174/156802611796904924] [PMID: 21671878]
[http://dx.doi.org/10.36076/ppj.2012/15/287] [PMID: 22828682]
[http://dx.doi.org/10.2174/1876386301306010095] [PMID: 26779292]
[http://dx.doi.org/10.1016/j.spinee.2010.03.029] [PMID: 20452292]
[http://dx.doi.org/10.1002/ptr.4972] [PMID: 23625885]
[http://dx.doi.org/10.1080/10408390601062054] [PMID: 17987447]
[http://dx.doi.org/10.1016/j.bbrc.2019.06.039] [PMID: 31213294]
[http://dx.doi.org/10.1038/sj.bjp.0706040] [PMID: 15685214]
[http://dx.doi.org/10.1039/C4OB02242D] [PMID: 25438036]
[http://dx.doi.org/10.1016/j.neuro.2020.04.008] [PMID: 32360092]
[http://dx.doi.org/10.1016/S0367-326X(01)00270-2] [PMID: 11543966]
[http://dx.doi.org/10.1016/j.intimp.2016.06.005] [PMID: 27355133]
[http://dx.doi.org/10.1177/154405910308201004] [PMID: 14514756]
[http://dx.doi.org/10.1007/s00221-018-5254-y] [PMID: 29654351]
[http://dx.doi.org/10.1016/S0896-6273(04)00150-3] [PMID: 15046718]
[http://dx.doi.org/10.1111/j.1365-2885.2006.00740.x] [PMID: 16846463]
[http://dx.doi.org/10.5958/j.0975-6892.5.1.004]
[http://dx.doi.org/10.1016/S0028-3908(03)00100-X] [PMID: 12726827]
[http://dx.doi.org/10.1016/S0165-6147(99)01393-0] [PMID: 10542446]
[http://dx.doi.org/10.1038/sj.bjp.0702440] [PMID: 10217528]
[http://dx.doi.org/10.1016/j.jgr.2017.09.001] [PMID: 29348728]
[http://dx.doi.org/10.1016/j.jgr.2018.12.012] [PMID: 32095092]
[http://dx.doi.org/10.1016/j.jgr.2020.02.004] [PMID: 33841000]
[http://dx.doi.org/10.1016/j.jgr.2017.02.005] [PMID: 29719465]
[http://dx.doi.org/10.1159/000448001] [PMID: 27441690]
[http://dx.doi.org/10.1007/978-3-319-05161-1_19]
[http://dx.doi.org/10.1016/j.intimp.2010.07.010] [PMID: 20678598]
[http://dx.doi.org/10.1016/j.tifs.2017.02.011]
[http://dx.doi.org/10.1142/S0192415X16500762] [PMID: 27785943]
[http://dx.doi.org/10.5348/ijcri-2013-02-267-RA-1]
[http://dx.doi.org/10.1023/A:1023988110064]
[http://dx.doi.org/10.1097/ALN.0b013e318249cf62] [PMID: 22314297]
[http://dx.doi.org/10.1016/j.jep.2009.10.004] [PMID: 19833188]
[http://dx.doi.org/10.1016/0028-3908(92)90013-F] [PMID: 1282221]
[http://dx.doi.org/10.1016/j.jep.2019.112396] [PMID: 31743763]
[http://dx.doi.org/10.1111/bph.14766] [PMID: 31207668]
[PMID: 32954562]
[http://dx.doi.org/10.22146/ijc.28172]
[http://dx.doi.org/10.1038/sj.bjp.0704925] [PMID: 12411409]
[http://dx.doi.org/10.1080/110284150600955164] [PMID: 17176640]
[http://dx.doi.org/10.1016/j.bmcl.2011.12.113] [PMID: 22257892]
[http://dx.doi.org/10.3390/nu12030872] [PMID: 32213941]
[http://dx.doi.org/10.1016/j.cub.2005.04.018] [PMID: 15916949]
[http://dx.doi.org/10.1038/nn2056] [PMID: 18297068]
[http://dx.doi.org/10.1016/j.fitote.2020.104668] [PMID: 32540378]
[http://dx.doi.org/10.1248/bpb.16.935] [PMID: 8268864]
[http://dx.doi.org/10.1007/s13577-019-00238-4] [PMID: 30701373]
[http://dx.doi.org/10.1007/978-3-319-41342-6_14]
[http://dx.doi.org/10.1007/s11418-015-0929-1] [PMID: 26188960]
[http://dx.doi.org/10.3390/molecules22060943] [PMID: 28598372]
[http://dx.doi.org/10.1002/mnfr.200900323] [PMID: 19960458]
[http://dx.doi.org/10.1124/mol.113.088997] [PMID: 24275229]
[http://dx.doi.org/10.1007/s00424-013-1334-9] [PMID: 23955021]
[http://dx.doi.org/10.1016/j.japh.2019.07.015] [PMID: 31495691]
[http://dx.doi.org/10.2174/157015906778019527] [PMID: 18615144]
[http://dx.doi.org/10.3390/ijms20236079] [PMID: 31810321]
[http://dx.doi.org/10.1007/978-3-030-48927-4_21]
[http://dx.doi.org/10.2174/0929867323666160627104453] [PMID: 27356539]
[http://dx.doi.org/10.2174/157015908783769644] [PMID: 19305789]
[http://dx.doi.org/10.1016/S0006-2952(02)01451-X] [PMID: 12473388]
[http://dx.doi.org/10.1016/j.cbi.2020.109178] [PMID: 32738201]
[http://dx.doi.org/10.1016/j.neulet.2005.09.046] [PMID: 16243435]
[PMID: 33165872]
[http://dx.doi.org/10.1016/j.bpj.2015.11.1537]
[http://dx.doi.org/10.3389/fimmu.2018.00174] [PMID: 29467763]
[http://dx.doi.org/10.1124/mol.62.4.947] [PMID: 12237342]
[http://dx.doi.org/10.3390/ijms22010004] [PMID: 33374919]
[http://dx.doi.org/10.1080/00397911.2017.1386789]
[http://dx.doi.org/10.2174/157015908784533888] [PMID: 19305794]
[http://dx.doi.org/10.2174/156802608786264254] [PMID: 18991729]
[http://dx.doi.org/10.1007/BF00389230] [PMID: 2426275]
[http://dx.doi.org/10.1016/j.phymed.2017.06.006] [PMID: 28899508]
[http://dx.doi.org/10.1002/ejoc.200400403]
[http://dx.doi.org/10.1016/j.jep.2018.11.035] [PMID: 30472402]
[http://dx.doi.org/10.1016/S0022-5347(01)63942-9] [PMID: 9649257]
[http://dx.doi.org/10.1016/j.ejphar.2003.11.039] [PMID: 14757119]
[http://dx.doi.org/10.1016/j.fertnstert.2017.07.929]
[http://dx.doi.org/10.1155/2021/8787231] [PMID: 33532012]
[http://dx.doi.org/10.1177/0022034509356169] [PMID: 20040737]
[http://dx.doi.org/10.1136/bmjsem-2020-000935] [PMID: 33500785]
[http://dx.doi.org/10.1016/j.phymed.2018.04.045] [PMID: 30195871]
[http://dx.doi.org/10.1021/bi051494l] [PMID: 16300403]
[http://dx.doi.org/10.3390/toxins9100326] [PMID: 29035314]