Abstract
Pain is generated by a small number of peripheral targets. These can be made more sensitive by inflammatory mediators. The number of opioids prescribed to the patients can be reduced dramatically with better pain management. Any therapy that safely and reliably provides extended analgesia and is flexible enough to facilitate a diverse array of release profiles would be useful for improving patient comfort, quality of care, and compliance after surgical procedures. Comparisons are made between new and traditional methods, and the current state of development has been discussed; taking into account the availability of molecular and cellular level data, preclinical and clinical data, and early post-market data. There are a number of benefits associated with the use of nanotechnology in the delivery of analgesics to specific areas of the body. Nanoparticles are able to transport drugs to inaccessible bodily areas because of their small molecular size. This review focuses on targets that act specifically or primarily on sensory neurons, as well as inflammatory mediators that have been shown to have an analgesic effect as a side effect of their anti- inflammatory properties. New, regulated post-operative pain management devices that use existing polymeric systems were presented in this article, along with the areas for potential development. Analgesic treatments, both pharmacological and non-pharmacological, have also been discussed.
Graphical Abstract
[http://dx.doi.org/10.1038/s41467-021-21438-3] [PMID: 33649338]
[http://dx.doi.org/10.3390/healthcare11010034] [PMID: 36611494]
[http://dx.doi.org/10.1002/bjs.11477] [PMID: 31903595]
[http://dx.doi.org/10.1001/jamanetworkopen.2021.0753] [PMID: 33724391]
[http://dx.doi.org/10.1038/s41598-022-24703-7] [PMID: 36414674]
[http://dx.doi.org/10.3389/fpubh.2023.1046683]
[http://dx.doi.org/10.3390/ijms24119223] [PMID: 37298174]
[http://dx.doi.org/10.1186/s12951-022-01473-y] [PMID: 35717383]
[http://dx.doi.org/10.1016/j.jconrel.2020.11.052] [PMID: 33278481]
[http://dx.doi.org/10.1126/science.aaf8924] [PMID: 27811267]
[http://dx.doi.org/10.1016/S0140-6736(06)68700-X] [PMID: 16698416]
[http://dx.doi.org/10.2174/1876386301306010190] [PMID: 24567767]
[http://dx.doi.org/10.1007/s00540-018-2579-4] [PMID: 30448975]
[http://dx.doi.org/10.1038/nm.2235] [PMID: 20948530]
[http://dx.doi.org/10.1038/nrn.2018.2] [PMID: 29416128]
[http://dx.doi.org/10.1055/s-0033-1351138] [PMID: 24436674]
[PMID: 20351978]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01434.x] [PMID: 21488863]
[http://dx.doi.org/10.7554/eLife.31106] [PMID: 28891794]
[http://dx.doi.org/10.3390/ijms20102488] [PMID: 31137507]
[http://dx.doi.org/10.1016/j.neuropharm.2017.06.015] [PMID: 28625720]
[http://dx.doi.org/10.1001/jama.2015.6358] [PMID: 26103030]
[http://dx.doi.org/10.1038/nn1916] [PMID: 17558404]
[http://dx.doi.org/10.1016/j.neuropharm.2018.07.002]
[http://dx.doi.org/10.1016/bs.apha.2017.05.003] [PMID: 28826543]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00516] [PMID: 27482723]
[http://dx.doi.org/10.1038/npp.2015.148] [PMID: 26052038]
[http://dx.doi.org/10.1016/j.biopsych.2017.06.032] [PMID: 28823711]
[http://dx.doi.org/10.1124/pr.109.001370] [PMID: 19805477]
[http://dx.doi.org/10.1038/s41422-020-0280-2] [PMID: 32047270]
[http://dx.doi.org/10.1038/s41594-020-0386-8] [PMID: 32157248]
[http://dx.doi.org/10.1177/1744806916646383] [PMID: 27175011]
[http://dx.doi.org/10.1016/j.jphs.2016.01.008] [PMID: 26948958]
[http://dx.doi.org/10.1016/j.jphs.2018.11.011] [PMID: 30552012]
[http://dx.doi.org/10.1186/s10194-018-0893-8] [PMID: 30088106]
[http://dx.doi.org/10.1016/j.ejmech.2019.111902] [PMID: 31771828]
[http://dx.doi.org/10.1016/j.neuropharm.2015.11.032] [PMID: 26700245]
[http://dx.doi.org/10.1021/cr078224o] [PMID: 18476671]
[http://dx.doi.org/10.1111/head.13582] [PMID: 31291016]
[http://dx.doi.org/10.2174/1568007043482570] [PMID: 14965240]
[http://dx.doi.org/10.1016/j.pain.2005.03.008]
[http://dx.doi.org/10.1177/0333102419889350] [PMID: 31744319]
[http://dx.doi.org/10.1097/j.pain.0000000000000319] [PMID: 26270581]
[http://dx.doi.org/10.1111/bph.14185] [PMID: 29486058]
[http://dx.doi.org/10.1016/j.bcp.2007.01.007]
[http://dx.doi.org/10.1111/bph.14696] [PMID: 31046146]
[http://dx.doi.org/10.1124/jpet.110.171264] [PMID: 20864501]
[http://dx.doi.org/10.1016/j.drudis.2014.05.007] [PMID: 24859018]
[http://dx.doi.org/10.4149/BLL_2012_145] [PMID: 23137201]
[http://dx.doi.org/10.1016/j.jaci.2018.07.047] [PMID: 30414855]
[http://dx.doi.org/10.1016/j.pain.2009.11.021] [PMID: 20031321]
[http://dx.doi.org/10.1523/JNEUROSCI.3249-15.2016] [PMID: 27147658]
[http://dx.doi.org/10.1073/pnas.1417365111] [PMID: 25385614]
[http://dx.doi.org/10.1111/cei.12338] [PMID: 24665841]
[http://dx.doi.org/10.1681/ASN.2016111179] [PMID: 28400446]
[http://dx.doi.org/10.1523/JNEUROSCI.5403-05.2006] [PMID: 16793879]
[http://dx.doi.org/10.1016/j.neuroscience.2019.12.003] [PMID: 31883821]
[http://dx.doi.org/10.1186/1742-2094-9-108] [PMID: 22642848]
[http://dx.doi.org/10.1021/jm800854e] [PMID: 19006379]
[http://dx.doi.org/10.1016/j.phrs.2014.11.004] [PMID: 25434589]
[http://dx.doi.org/10.2174/0929867324666170713102514] [PMID: 28707588]
[http://dx.doi.org/10.1152/physrev.00052.2017] [PMID: 30672368]
[http://dx.doi.org/10.1016/S0896-6273(00)81133-2] [PMID: 10798388]
[http://dx.doi.org/10.1007/s00424-009-0779-3] [PMID: 20101409]
[http://dx.doi.org/10.1016/j.jpain.2004.04.005] [PMID: 15219259]
[http://dx.doi.org/10.1016/0896-6273(95)90317-8] [PMID: 7695907]
[http://dx.doi.org/10.1073/pnas.0404915101] [PMID: 15314237]
[http://dx.doi.org/10.1097/j.pain.0000000000001602] [PMID: 31095098]
[http://dx.doi.org/10.1111/bph.13962] [PMID: 28749537]
[http://dx.doi.org/10.2147/JPR.S207610] [PMID: 31564962]
[http://dx.doi.org/10.1007/s00210-018-1487-3] [PMID: 29572558]
[http://dx.doi.org/10.1038/d41573-019-00065-0] [PMID: 31048807]
[http://dx.doi.org/10.1080/13543784.2020.1728254]
[http://dx.doi.org/10.1113/jphysiol.2010.200717] [PMID: 21078588]
[http://dx.doi.org/10.1016/j.drudis.2018.06.020] [PMID: 29969684]
[http://dx.doi.org/10.4324/9781315152837-8]
[http://dx.doi.org/10.3389/fphys.2017.01040] [PMID: 29326595]
[http://dx.doi.org/10.1016/j.pain.2008.02.022] [PMID: 18381233]
[http://dx.doi.org/10.1016/j.neuron.2012.12.016] [PMID: 23439120]
[http://dx.doi.org/10.1073/pnas.0902675106] [PMID: 19897733]
[http://dx.doi.org/10.1016/0006-8993(87)90982-6] [PMID: 3664271]
[http://dx.doi.org/10.1093/brain/112.5.1317] [PMID: 2804614]
[http://dx.doi.org/10.1113/jphysiol.1992.sp019068] [PMID: 1593488]
[http://dx.doi.org/10.1016/0304-3959(89)90079-1] [PMID: 2780068]
[http://dx.doi.org/10.3390/molecules21080966] [PMID: 27455231]
[http://dx.doi.org/10.1007/s40265-015-0520-9] [PMID: 26666418]
[http://dx.doi.org/10.1080/23328940.2015.1046013] [PMID: 27227030]
[http://dx.doi.org/10.1155/2016/5259321] [PMID: 27738388]
[http://dx.doi.org/10.1016/j.pharmthera.2020.107474] [PMID: 31926897]
[http://dx.doi.org/10.1002/anie.201302530] [PMID: 23873837]
[http://dx.doi.org/10.3390/ijms20143411] [PMID: 31336748]
[http://dx.doi.org/10.1124/pr.55.4.9] [PMID: 14657415]
[http://dx.doi.org/10.2174/1570159X113119990042] [PMID: 24396338]
[http://dx.doi.org/10.1097/SPC.0000000000000131] [PMID: 25872119]
[http://dx.doi.org/10.1093/oxfordhb/9780190860509.013.19]
[http://dx.doi.org/10.1152/jn.1998.79.4.1814] [PMID: 9535950]
[http://dx.doi.org/10.1016/j.pain.2014.08.025] [PMID: 25168672]
[http://dx.doi.org/10.1111/bph.14518] [PMID: 30325008]
[http://dx.doi.org/10.1111/bph.14098] [PMID: 29150838]
[http://dx.doi.org/10.1016/j.neuropharm.2018.07.026] [PMID: 30056126]
[http://dx.doi.org/10.1038/nature22988] [PMID: 28693035]
[http://dx.doi.org/10.1016/j.bbrc.2013.10.090] [PMID: 24383077]
[http://dx.doi.org/10.4161/chan.5.5.16469] [PMID: 21829087]
[http://dx.doi.org/10.3389/fnins.2020.00287] [PMID: 32322187]
[http://dx.doi.org/10.1152/jn.01007.2007] [PMID: 18385481]
[http://dx.doi.org/10.1016/S0306-4522(99)00101-3] [PMID: 10465455]
[http://dx.doi.org/10.1523/JNEUROSCI.20-20-07531.2000] [PMID: 11027211]
[http://dx.doi.org/10.1016/j.pain.2004.12.023] [PMID: 15733649]
[http://dx.doi.org/10.1186/1744-8069-4-32] [PMID: 18700020]
[http://dx.doi.org/10.1038/31255] [PMID: 9634236]
[http://dx.doi.org/10.1016/j.neuroscience.2009.04.063]
[http://dx.doi.org/10.1113/JP278211] [PMID: 31290157]
[http://dx.doi.org/10.1097/j.pain.0000000000001005] [PMID: 28767511]
[http://dx.doi.org/10.1016/j.pain.2014.05.021] [PMID: 24861581]
[http://dx.doi.org/10.1097/j.pain.0000000000001638] [PMID: 31188268]
[http://dx.doi.org/10.3389/fphar.2018.01252] [PMID: 30467478]
[http://dx.doi.org/10.1152/jn.00676.2003] [PMID: 14657190]
[http://dx.doi.org/10.1152/jn.01350.2007] [PMID: 18337362]
[http://dx.doi.org/10.1523/JNEUROSCI.19-06-02181.1999] [PMID: 10066271]
[http://dx.doi.org/10.1016/S0079-6123(00)29005-5] [PMID: 11098681]
[http://dx.doi.org/10.1523/JNEUROSCI.17-19-07462.1997] [PMID: 9295392]
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3313] [PMID: 22781553]
[http://dx.doi.org/10.1016/j.semcancer.2017.05.011]
[http://dx.doi.org/10.1126/science.1072682] [PMID: 12471242]
[http://dx.doi.org/10.1016/j.brainresrev.2008.12.011] [PMID: 19150373]
[http://dx.doi.org/10.1016/j.neulet.2008.03.017]
[http://dx.doi.org/10.1038/nrd1177] [PMID: 12951578]
[http://dx.doi.org/10.2174/0929867321666140915143040] [PMID: 25245374]
[http://dx.doi.org/10.1523/JNEUROSCI.22-17-07737.2002] [PMID: 12196597]
[http://dx.doi.org/10.1523/JNEUROSCI.23-10-04117.2003] [PMID: 12764099]
[http://dx.doi.org/10.1371/journal.pone.0225586] [PMID: 31765435]
[http://dx.doi.org/10.1016/j.jconrel.2009.07.016] [PMID: 19665039]
[http://dx.doi.org/10.1097/ACO.0000000000001123] [PMID: 35283459]
[http://dx.doi.org/10.1016/S0304-3959(98)00244-9] [PMID: 10342414]
[http://dx.doi.org/10.1007/s40265-018-0982-7] [PMID: 30251173]
[http://dx.doi.org/10.1093/bja/aei144] [PMID: 15833778]
[http://dx.doi.org/10.1097/j.pain.0000000000001322] [PMID: 29965830]
[http://dx.doi.org/10.1001/jamasurg.2014.210] [PMID: 25317633]
[http://dx.doi.org/10.1111/anae.13495] [PMID: 27079158]
[http://dx.doi.org/10.1001/jamasurg.2017.0898] [PMID: 28564673]
[http://dx.doi.org/10.1213/00000539-199311000-00030] [PMID: 8105724]
[http://dx.doi.org/10.1093/bja/aeq406] [PMID: 21285082]
[PMID: 26414123]
[http://dx.doi.org/10.1016/j.pain.2012.12.025] [PMID: 23433945]
[http://dx.doi.org/10.1592/phco.27.9.1219] [PMID: 17723075]
[http://dx.doi.org/10.1146/annurev-neuro-080317-061522] [PMID: 29852083]
[http://dx.doi.org/10.1016/j.coph.2008.12.009] [PMID: 19157985]
[http://dx.doi.org/10.1001/jamasurg.2018.1039] [PMID: 29799927]
[http://dx.doi.org/10.1016/j.jpain.2016.11.001] [PMID: 27919771]
[http://dx.doi.org/10.1001/jamasurg.2017.0831] [PMID: 28768328]
[http://dx.doi.org/10.1016/j.pmn.2018.07.003] [PMID: 30172738]
[http://dx.doi.org/10.1097/PR9.0000000000000611] [PMID: 29392226]
[http://dx.doi.org/10.1177/0310057X1103900505] [PMID: 21970125]
[http://dx.doi.org/10.1213/ANE.0000000000002497] [PMID: 29049119]
[http://dx.doi.org/10.1016/j.pain.2012.11.005] [PMID: 23265688]
[http://dx.doi.org/10.1016/j.tins.2009.07.007] [PMID: 19781793]
[http://dx.doi.org/10.1007/s00268-018-4844-y] [PMID: 30426190]
[http://dx.doi.org/10.1136/ijgc-2019-000356] [PMID: 30877144]
[http://dx.doi.org/10.1007/s00268-018-4786-4] [PMID: 30276441]
[http://dx.doi.org/10.1007/s00268-016-3492-3] [PMID: 26943657]
[http://dx.doi.org/10.1097/PRS.0000000000003242] [PMID: 28445352]
[http://dx.doi.org/10.1002/bjs.9614] [PMID: 25091299]
[http://dx.doi.org/10.1007/s00268-016-3727-3] [PMID: 27766396]
[http://dx.doi.org/10.1002/14651858.CD011274.pub2] [PMID: 30488949]
[http://dx.doi.org/10.1016/j.ejso.2017.06.010] [PMID: 28687432]
[http://dx.doi.org/10.1111/ans.14322] [PMID: 29164809]
[http://dx.doi.org/10.1007/s00464-018-6355-1] [PMID: 29998389]
[http://dx.doi.org/10.1002/14651858.CD012033.pub4] [PMID: 30570761]
[http://dx.doi.org/10.1177/0091270009337941] [PMID: 19546251]
[PMID: 23881791]
[http://dx.doi.org/10.1016/j.bja.2018.02.066] [PMID: 29793598]
[http://dx.doi.org/10.1213/ANE.0b013e318249d36e] [PMID: 22415535]
[http://dx.doi.org/10.1213/01.ane.0000261517.27532.80] [PMID: 17513656]
[http://dx.doi.org/10.1111/aas.12766] [PMID: 27426431]
[http://dx.doi.org/10.1093/bja/aex227] [PMID: 29121288]
[http://dx.doi.org/10.1136/bmj.k4364] [PMID: 30327316]
[http://dx.doi.org/10.1007/s40265-017-0700-x] [PMID: 28144823]
[http://dx.doi.org/10.1111/anae.14657] [PMID: 30950522]
[http://dx.doi.org/10.1002/14651858.CD010358.pub2] [PMID: 26889627]
[http://dx.doi.org/10.1186/s13741-017-0064-5] [PMID: 28413629]
[http://dx.doi.org/10.1097/ALN.0b013e318297630d] [PMID: 23669270]
[http://dx.doi.org/10.1155/2014/236024] [PMID: 24772415]
[PMID: 24649780]
[http://dx.doi.org/10.1002/14651858.CD008646.pub2] [PMID: 27228096]
[http://dx.doi.org/10.1016/j.pmn.2017.09.003] [PMID: 29153918]
[PMID: 16625614]
[http://dx.doi.org/10.1016/j.jopan.2016.12.003] [PMID: 29157760]
[PMID: 29477136]
[http://dx.doi.org/10.1089/cyber.2017.0714] [PMID: 30256662]
[http://dx.doi.org/10.1155/2016/9704185] [PMID: 27445635]
[http://dx.doi.org/10.3390/polym10121379] [PMID: 30961303]
[http://dx.doi.org/10.2165/11591290-000000000-00000] [PMID: 21668037]
[http://dx.doi.org/10.2147/DDDT.S165440] [PMID: 30288019]
[http://dx.doi.org/10.1021/bc8000479] [PMID: 18717537]
[http://dx.doi.org/10.1080/09205063.2013.849904] [PMID: 24156311]
[http://dx.doi.org/10.1016/j.carbpol.2017.05.040] [PMID: 28606546]
[http://dx.doi.org/10.1155/2019/6062381]
[http://dx.doi.org/10.1002/adhm.201300521] [PMID: 24376136]
[http://dx.doi.org/10.1016/j.jconrel.2006.10.014] [PMID: 17137669]
[http://dx.doi.org/10.1016/0168-3659(94)90029-9]
[http://dx.doi.org/10.1371/journal.pone.0186784] [PMID: 29059223]
[http://dx.doi.org/10.1016/j.polymer.2017.03.016]
[http://dx.doi.org/10.1016/S0169-409X(02)00056-X] [PMID: 12384320]
[PMID: 27274236]
[http://dx.doi.org/10.2147/IJN.S190164] [PMID: 30774342]
[http://dx.doi.org/10.1016/j.biomaterials.2018.07.032] [PMID: 30458361]
[http://dx.doi.org/10.1038/s41467-019-10296-9] [PMID: 31189915]
[http://dx.doi.org/10.1097/ALN.0b013e3181d4f66f] [PMID: 20461003]
[http://dx.doi.org/10.1016/j.biomaterials.2014.05.064] [PMID: 24952978]
[http://dx.doi.org/10.2147/IJN.S189505] [PMID: 30573957]
[http://dx.doi.org/10.1007/s00289-019-02727-w]
[http://dx.doi.org/10.1007/s10544-012-9637-8] [PMID: 22374474]
[http://dx.doi.org/10.1016/j.jphotobiol.2019.111530] [PMID: 31279287]
[http://dx.doi.org/10.1016/j.msec.2016.01.021] [PMID: 26952404]
[http://dx.doi.org/10.1016/j.jconrel.2016.11.003] [PMID: 27836707]
[http://dx.doi.org/10.1016/S0142-9612(02)00181-3] [PMID: 12219831]
[http://dx.doi.org/10.1016/S0169-409X(02)00053-4] [PMID: 12384317]
[http://dx.doi.org/10.1016/j.biomaterials.2007.05.034] [PMID: 17576005]
[http://dx.doi.org/10.1016/j.biomaterials.2013.12.025] [PMID: 24388799]
[http://dx.doi.org/10.1007/s002800050588] [PMID: 9054951]
[http://dx.doi.org/10.1016/S0168-3659(99)00218-7] [PMID: 10699295]
[http://dx.doi.org/10.1016/S0168-3659(00)00348-5] [PMID: 11245906]
[http://dx.doi.org/10.1002/polb.22259] [PMID: 21769165]
[http://dx.doi.org/10.1016/0030-4220(71)90265-9] [PMID: 5281553]
[http://dx.doi.org/10.1002/jbm.820050207] [PMID: 5575328]
[http://dx.doi.org/10.1016/j.actbio.2013.06.003] [PMID: 23770220]
[http://dx.doi.org/10.1021/acsami.6b00874] [PMID: 26936629]
[http://dx.doi.org/10.1016/j.jconrel.2012.01.017] [PMID: 22342473]
[http://dx.doi.org/10.1021/acsabm.1c00422] [PMID: 35007011]
[http://dx.doi.org/10.1016/j.apsusc.2022.156108]
[http://dx.doi.org/10.1007/s10853-022-08103-w]
[http://dx.doi.org/10.1002/jcb.20796] [PMID: 16440317]
[http://dx.doi.org/10.1016/j.nano.2004.11.009] [PMID: 17292054]
[http://dx.doi.org/10.4314/tjpr.v8i3.44547]
[PMID: 21720511]
[http://dx.doi.org/10.1016/j.jconrel.2009.10.016] [PMID: 19850095]
[http://dx.doi.org/10.1007/s11481-006-9032-4] [PMID: 18040810]
[http://dx.doi.org/10.2174/1381612821666151027152752] [PMID: 26503147]
[http://dx.doi.org/10.1016/S0006-291X(02)00445-X] [PMID: 12054749]
[http://dx.doi.org/10.1016/S0968-0896(02)00049-4] [PMID: 11937359]
[http://dx.doi.org/10.2174/1381612821666150428145216] [PMID: 25925113]
[http://dx.doi.org/10.1081/DIS-120021801]
[http://dx.doi.org/10.3109/10731199.2011.637924] [PMID: 22192072]
[http://dx.doi.org/10.2217/nnm.15.23] [PMID: 26080700]
[http://dx.doi.org/10.1016/j.ijpharm.2016.06.016] [PMID: 27286632]
[http://dx.doi.org/10.2147/IJN.S61288] [PMID: 24872687]
[http://dx.doi.org/10.1016/j.jconrel.2014.03.053] [PMID: 24747160]
[http://dx.doi.org/10.4103/2230-973X.96920] [PMID: 23071954]
[http://dx.doi.org/10.1081/DDC-52073] [PMID: 15830725]
[http://dx.doi.org/10.7555/JBR.27.20120136] [PMID: 24683406]