Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Neuropharmacology
  4. Volume 22, Issue 1
  5. Article
Volume 22, Issue 1
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

In the current management of neuropathic pain, in addition to antidepressants and anticonvulsants, the use of opioids is wide, despite their related and well-known issues.

-palmitoylethanolamine (PEA), a natural fatty-acid ethanolamide whose anti-inflammatory, neuroprotective, immune-modulating and anti-hyperalgesic activities are known, represents a promising candidate to modulate and/or potentiate the action of opioids.

This study was designed to evaluate if the preemptive and morphine concomitant administration of ultramicronized PEA, according to fixed or increasing doses of both compounds, delays the onset of morphine tolerance and improves its analgesic efficacy in the chronic constriction injury (CCI) model of neuropathic pain in rats.

Behavioral experiments showed that the preemptive and co-administration of ultramicronized PEA significantly decreased the effective dose of morphine and delayed the onset of morphine tolerance. The activation of spinal microglia and astrocytes, commonly occurring both on opioid treatment and neuropathic pain, was investigated through GFAP and Iba-1 immunofluorescence. Both biomarkers were found to be increased in CCI untreated or morphine treated animals in a PEA-sensitive manner. The increased density of endoneural mast cells within the sciatic nerve of morphine-treated and untreated CCI rats was significantly reduced by ultramicronized PEA. The decrease of mast cell degranulation, evaluated in terms of reduced plasma levels of histamine and N-methyl-histamine metabolite, was mainly observed at intermediate-high doses of ultramicronized PEA, with or without morphine.

Overall, these results show that the administration of ultramicronized PEA in CCI rats according to the study design fully fulfilled the hypotheses of this study.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X21666221128091453
2024-01-01
2024-10-13

  • From This Site

    /content/journals/cn/10.2174/1570159X21666221128091453
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. TreedeR.D. JensenT.S. CampbellJ.N. CruccuG. DostrovskyJ.O. GriffinJ.W. HanssonP. HughesR. NurmikkoT. SerraJ. Neuropathic pain: Redefinition and a grading system for clinical and research purposes.Neurology200870181630163510.1212/01.wnl.0000282763.29778.5918003941
     [Google Scholar]
  2. CollocaL. LudmanT. BouhassiraD. BaronR. DickensonA.H. YarnitskyD. FreemanR. TruiniA. AttalN. FinnerupN.B. EcclestonC. KalsoE. BennettD.L. DworkinR.H. RajaS.N. Neuropathic pain.Nat. Rev. Dis. Primers2017311700210.1038/nrdp.2017.228205574
     [Google Scholar]
  3. SmithB.H. HébertH.L. VeluchamyA. Neuropathic pain in the community: Prevalence, impact, and risk factors.Pain2020161Suppl. 1S127S13710.1097/j.pain.000000000000182433090746
     [Google Scholar]
  4. FinnerupN.B. AttalN. HaroutounianS. McNicolE. BaronR. DworkinR.H. GilronI. HaanpääM. HanssonP. JensenT.S. KamermanP.R. LundK. MooreA. RajaS.N. RiceA.S.C. RowbothamM. SenaE. SiddallP. SmithB.H. WallaceM. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis.Lancet Neurol.201514216217310.1016/S1474‑4422(14)70251‑025575710
     [Google Scholar]
  5. SerranoA. CarnavalT. Videla CésS. Combination therapy for neuropathic pain: A review of recent evidence.J. Clin. Med.20211016353310.3390/jcm1016353334441829
     [Google Scholar]
  6. NudellY. DymH. SunF. BenichouM. MalakanJ. HalpernL.R. Pharmacologic management of neuropathic pain.Oral Maxillofac. Surg. Clin. North Am.2022341618110.1016/j.coms.2021.09.00234802616
     [Google Scholar]
  7. SommerC. KloseP. WelschP. PetzkeF. HäuserW. Opioids for chronic non‐cancer neuropathic pain. An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks duration.Eur. J. Pain202024131810.1002/ejp.149431705717
     [Google Scholar]
  8. KuehlF.A.Jr JacobT.A. GanleyO.H. OrmondR.E. MeisingerM.A.P. The identification of N-(2-hydroxyethyl)-palmitoile as a naturally occuring anti-inflammatory agent.J. Am. Chem. Soc.195779205577557810.1021/ja01577a066
     [Google Scholar]
  9. AloeL. LeonA. Levi-MontalciniR. A proposed autacoid mechanism controlling mastocyte behaviour.Agents Actions199339S1C145C14710.1007/BF019727487505999
     [Google Scholar]
  10. Di Cesare MannelliL. CortiF. MicheliL. ZanardelliM. GhelardiniC. Delay of morphine tolerance by palmitoylethanolamide.BioMed Res. Int.2015201511210.1155/2015/89473225874232
     [Google Scholar]
  11. Di Cesare MannelliL. D’AgostinoG. PaciniA. RussoR. ZanardelliM. GhelardiniC. CalignanoA. Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-alpha-mediated mechanism.Mediators Inflamm.2013201311210.1155/2013/32879723533304
     [Google Scholar]
  12. Di Cesare MannelliL. PaciniA. CortiF. BoccellaS. LuongoL. EspositoE. CuzzocreaS. MaioneS. CalignanoA. GhelardiniC. Antineuropathic profile of N-palmitoylethanolamine in a rat model of oxaliplatin-induced neurotoxicity.PLoS One2015106e012808010.1371/journal.pone.012808026039098
     [Google Scholar]
  13. Di Cesare MannelliL. MicheliL. LucariniE. GhelardiniC. Ultramicronized N-palmitoylethanolamine supplementation for long-lasting, low-dosed morphine antinociception.Front. Pharmacol.2018947310.3389/fphar.2018.0047329910726
     [Google Scholar]
  14. SkaperS.D. FacciL. BarbieratoM. ZussoM. BruschettaG. ImpellizzeriD. CuzzocreaS. GiustiP. N-palmitoylethanolamine and neuroinflammation: A novel therapeutic strategy of resolution.Mol. Neurobiol.20155221034104210.1007/s12035‑015‑9253‑826055231
     [Google Scholar]
  15. PeritoreA.F. SiracusaR. FuscoR. GugliandoloE. D’AmicoR. CordaroM. CrupiR. GenoveseT. ImpellizzeriD. CuzzocreaS. Di PaolaR. Ultramicronized palmitoylethanolamide and paracetamol, a new association to relieve hyperalgesia and pain in a sciatic nerve injury model in rat.Int. J. Mol. Sci.20202110350910.3390/ijms2110350932429243
     [Google Scholar]
  16. ClaytonP. HillM. BogodaN. SubahS. VenkateshR. Palmitoylethanolamide: A natural compound for health management.Int. J. Mol. Sci.20212210530510.3390/ijms2210530534069940
     [Google Scholar]
  17. ArdizzoneA. FuscoR. CasiliG. LanzaM. ImpellizzeriD. EspositoE. CuzzocreaS. Effect of ultra-micronized-palmitoylethanolamide and acetyl-l-carnitine on experimental model of inflammatory pain.Int. J. Mol. Sci.2021224196710.3390/ijms2204196733671213
     [Google Scholar]
  18. PetrosinoS. PalazzoE. de NovellisV. BisognoT. RossiF. MaioneS. Di MarzoV. Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats.Neuropharmacology200752241542210.1016/j.neuropharm.2006.08.01117011598
     [Google Scholar]
  19. CongiuM. MicheliL. SantoniM. SaghedduC. MuntoniA.L. MakriyannisA. MalamasM.S. GhelardiniC. Di Cesare MannelliL. PistisM. N-Acylethanolamine acid amidase inhibition potentiates morphine analgesia and delays the development of tolerance.Neurotherapeutics20211842722273610.1007/s13311‑021‑01116‑434553321
     [Google Scholar]
  20. McGrathJ.C. LilleyE. Implementing guidelines on reporting research using animals (ARRIVE etc.): New requirements for publication in BJP.Br. J. Pharmacol.2015172133189319310.1111/bph.1295525964986
     [Google Scholar]
  21. BennettG.J. XieY.K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.Pain19883318710710.1016/0304‑3959(88)90209‑62837713
     [Google Scholar]
  22. LeightonG.E. Rodriguez, R.E.; Hill, R.G.; Hughes, J. κ-Opioid agonists produce antinociception after i.v. and i.c.v. but not intrathecal administration in the rat.Br. J. Pharmacol.198893355356010.1111/j.1476‑5381.1988.tb10310.x2836010
     [Google Scholar]
  23. Di Cesare MannelliL. PaciniA. BonacciniL. ZanardelliM. MelloT. GhelardiniC. Morphologic features and glial activation in rat oxaliplatin-dependent neuropathic pain.J. Pain201314121585160010.1016/j.jpain.2013.08.00224135431
     [Google Scholar]
  24. Di Cesare MannelliL. MarescaM. MicheliL. FarinaC. ScherzM.W. GhelardiniC. A rat model of FOLFOX-induced neuropathy: Effects of oral dimiracetam in comparison with duloxetine and pregabalin.Cancer Chemother. Pharmacol.20178061091110310.1007/s00280‑017‑3449‑829026967
     [Google Scholar]
  25. DiC.M.L. MicheliL. ZanardelliM. GhelardiniC. Low dose native type II collagen prevents pain in a rat osteoarthritis model.BMC Musculoskelet. Disord.201314122810.1186/1471‑2474‑14‑22823915264
     [Google Scholar]
  26. MarescaM. MicheliL. CinciL. BiliaA.R. GhelardiniC. DiC.M.L. Pain relieving and protective effects of Astragalus hydroalcoholic extract in rat arthritis models.J. Pharm. Pharmacol.201769121858187010.1111/jphp.1282828960309
     [Google Scholar]
  27. ItoD. ImaiY. OhsawaK. NakajimaK. FukuuchiY. KohsakaS. Microglia-specific localisation of a novel calcium binding protein, Iba1.Brain Res. Mol. Brain Res.19985711910.1016/S0169‑328X(98)00040‑09630473
     [Google Scholar]
  28. Ben SaadR. HarbaouiM. Ben RomdhaneW. ZouariN. GiangK.N. Ben HsounaA. BriniF. Overexpression of triticum durum TdAnn12 gene confers stress tolerance through scavenging reactive oxygen species in transgenic tobacco.Funct. Plant Biol.2019461088589510.1071/FP1831631196377
     [Google Scholar]
  29. MicheliL. LucariniE. TotiA. FerraraV. CiampiC. ParisioC. BartolucciG. Di Cesare MannelliL. GhelardiniC. Effects of ultramicronized N-palmitoylethanolamine supplementation on tramadol and oxycodone analgesia and tolerance prevention.Pharmaceutics202214240310.3390/pharmaceutics1402040335214131
     [Google Scholar]
  30. YawnB.P. WollanP.C. WeingartenT.N. WatsonJ.C. HootenW.M. MeltonL.J.III The prevalence of neuropathic pain: Clinical evaluation compared with screening tools in a community population.Pain Med.200910358659310.1111/j.1526‑4637.2009.00588.x20849570
     [Google Scholar]
  31. DiBonaventuraM. SadoskyA. ConcialdiK. HoppsM. KudelI. ParsonsB. CappelleriJ.C. HlavacekP. AlexanderA. StaceyB.R. MarkmanJ.D. FarrarJ.T. The prevalence of probable neuropathic pain in the US: Results from a multimodal general-population health survey.J. Pain Res.2017102525253810.2147/JPR.S12701429138590
     [Google Scholar]
  32. D’AmicoR. ImpellizzeriD. CuzzocreaS. Di PaolaR. Aliamides update: Palmitoylethanolamide and its formulations on management of peripheral neuropathic pain.Int. J. Mol. Sci.20202115533010.3390/ijms2115533032727084
     [Google Scholar]
  33. AlessioN. BelardoC. TrottaM.C. PainoS. BoccellaS. GarganoF. PierettiG. RicciardiF. MarabeseI. LuongoL. GalderisiU. D’AmicoM. MaioneS. GuidaF. Vitamin D deficiency induces chronic pain and microglial phenotypic changes in mice.Int. J. Mol. Sci.2021227360410.3390/ijms2207360433808491
     [Google Scholar]
  34. D’AloiaA. MolteniL. GulloF. BrescianiE. ArtusaV. RizziL. CerianiM. MeantiR. LecchiM. CocoS. CostaB. TorselloA. Palmitoylethanolamide modulation of microglia activation: Characterization of mechanisms of action and implication for its neuroprotective effects.Int. J. Mol. Sci.2021226305410.3390/ijms2206305433802689
     [Google Scholar]
  35. MaioneS. CostaB. Di MarzoV. Endocannabinoids: A unique opportunity to develop multitarget analgesics.Pain2013154Suppl. 1S87S9310.1016/j.pain.2013.03.02323623250
     [Google Scholar]
  36. Lo VermeJ. FuJ. AstaritaG. La RanaG. RussoR. CalignanoA. PiomelliD. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide.Mol. Pharmacol.2005671151910.1124/mol.104.00635315465922
     [Google Scholar]
  37. RybergE. LarssonN. SjögrenS. HjorthS. HermanssonN-O. LeonovaJ. ElebringT. NilssonK. DrmotaT. GreasleyP.J. The orphan receptor GPR55 is a novel cannabinoid receptor.Br. J. Pharmacol.200715271092110110.1038/sj.bjp.070746017876302
     [Google Scholar]
  38. De PetrocellisL. DavisJ.B. Di MarzoV. Palmitoylethanolamide enhances anandamide stimulation of human vanilloid VR1 receptors.FEBS Lett.2001506325325610.1016/S0014‑5793(01)02934‑911602256
     [Google Scholar]
  39. DiM.A.R.Z.O. V.; Melck, D.; Orlando, P.; Bisogno, T.; Zagoory, O.; Bifulco, M.; Vogel, Z.; de Petrocellis, L. Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cells.Biochem. J.2001358124925510.1042/bj358024911485574
     [Google Scholar]
  40. HoW-S.V. BarrettD.A. RandallM.D. ‘Entourage’ effects of N -palmitoylethanolamide and N -oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors.Br. J. Pharmacol.2008155683784610.1038/bjp.2008.32418695637
     [Google Scholar]
  41. PetrosinoS. Schiano MorielloA. CerratoS. FuscoM. PuigdemontA. De PetrocellisL. Di MarzoV. The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels.Br. J. Pharmacol.201617371154116210.1111/bph.1308425598150
     [Google Scholar]
  42. SkaperS.D. Di MarzoV. Endocannabinoids in nervous system health and disease: The big picture in a nutshell.Philos. Trans. R. Soc. Lond. B Biol. Sci.201236716073193320010.1098/rstb.2012.031323108539
     [Google Scholar]
  43. DeuisJ.R. DvorakovaL.S. VetterI. Methods used to evaluate pain behaviors in rodents.Front. Mol. Neurosci.20171028410.3389/fnmol.2017.0028428932184
     [Google Scholar]
  44. HendersonG. The μ-opioid receptor: An electrophysiologist’s perspective from the sharp end.Br. J. Pharmacol.2015172226026710.1111/bph.1263324640948
     [Google Scholar]
  45. IwaiS. KiguchiN. KobayashiY. FukazawaY. SaikaF. UenoK. YamamotoC. KishiokaS. Inhibition of morphine tolerance is mediated by painful stimuli via central mechanisms.Drug Discov. Ther.201261313710.5582/ddt.2012.v6.1.3122460426
     [Google Scholar]
  46. XuJ.T. ZhaoJ.Y. ZhaoX. LigonsD. TiwariV. AtianjohF.E. LeeC.Y. LiangL. ZangW. NjokuD. RajaS.N. YasterM. TaoY.X. Opioid receptor–triggered spinal mTORC1 activation contributes to morphine tolerance and hyperalgesia.J. Clin. Invest.2014124259260310.1172/JCI7023624382350
     [Google Scholar]
  47. WilliamsJ.T. IngramS.L. HendersonG. ChavkinC. von ZastrowM. SchulzS. KochT. EvansC.J. ChristieM.J. Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacol. Rev.201365122325410.1124/pr.112.00594223321159
     [Google Scholar]
  48. CahillC.M. TaylorA.M.W. Neuroinflammation—a co-occurring phenomenon linking chronic pain and opioid dependence.Curr. Opin. Behav. Sci.20171317117710.1016/j.cobeha.2016.12.00328451629
     [Google Scholar]
  49. DeLeoJ.A. TangaF.Y. TawfikV.L. Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia.Neuroscientist2004104052
     [Google Scholar]
  50. RansohoffR.M. How neuroinflammation contributes to neurodegeneration.Science2016353630177778310.1126/science.aag2590
     [Google Scholar]
  51. SalterM.W. StevensB. Microglia emerge as central players in brain disease.Nat. Med.20172391018102710.1038/nm.439728886007
     [Google Scholar]
  52. FerriniF. TrangT. MattioliT.A.M. LaffrayS. Del’GuidiceT. LorenzoL.E. CastonguayA. DoyonN. ZhangW. GodinA.G. MohrD. BeggsS. VandalK. BeaulieuJ.M. CahillC.M. SalterM.W. De KoninckY. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis.Nat. Neurosci.201316218319210.1038/nn.329523292683
     [Google Scholar]
  53. VaccaV. MarinelliS. LuvisettoS. PavoneF. Botulinum toxin A increases analgesic effects of morphine, counters development of morphine tolerance and modulates glia activation and μ opioid receptor expression in neuropathic mice.Brain Behav. Immun.201332405010.1016/j.bbi.2013.01.08823402794
     [Google Scholar]
  54. MachelskaH. CelikM.Ö. Opioid receptors in immune and glial cells—implications for pain control.Front. Immunol.20201130010.3389/fimmu.2020.0030032194554
     [Google Scholar]
  55. HutchinsonM.R. BlandS.T. JohnsonK.W. RiceK.C. MaierS.F. WatkinsL.R. Opioid-induced glial activation: Mechanisms of activation and implications for opioid analgesia, dependence, and reward.Sci. World J.200779811110.1100/tsw.2007.23017982582
     [Google Scholar]
  56. WangX. LoramL.C. RamosK. de JesusA.J. ThomasJ. ChengK. ReddyA. SomogyiA.A. HutchinsonM.R. WatkinsL.R. YinH. Morphine activates neuroinflammation in a manner parallel to endotoxin.Proc. Natl. Acad. Sci. USA2012109166325633010.1073/pnas.120013010922474354
     [Google Scholar]
  57. EidsonL.N. MurphyA.Z. Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.Peptides2019115515810.1016/j.peptides.2019.01.00330890355
     [Google Scholar]
  58. BertaT. LiuY.C. XuZ.Z. JiR.R. Tissue plasminogen activator contributes to morphine tolerance and induces mechanical allodynia via astrocytic IL-1β and ERK signaling in the spinal cord of mice.Neuroscience201324737638510.1016/j.neuroscience.2013.05.01823707980
     [Google Scholar]
  59. TavesS. BertaT. ChenG. JiR.R. Microglia and spinal cord synaptic plasticity in persistent pain.Neural Plast.2013201311010.1155/2013/75365624024042
     [Google Scholar]
  60. MatejukA. RansohoffR.M. Crosstalk between astrocytes and microglia: An overview.Front. Immunol.202011141610.3389/fimmu.2020.0141632765501
     [Google Scholar]
  61. MazzariS. CanellaR. PetrelliL. MarcolongoG. LeonA.N. -(2-Hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation.Eur. J. Pharmacol.1996300322723610.1016/0014‑2999(96)00015‑58739213
     [Google Scholar]
  62. CostaB. ComelliF. BettoniI. ColleoniM. GiagnoniG. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors.Pain2008139354155010.1016/j.pain.2008.06.00318602217
     [Google Scholar]
  63. IuvoneT. AffaitatiG. De FilippisD. LopopoloM. GrassiaG. LapennaD. NegroL. CostantiniR. VaiaM. CipolloneF. IalentiA. GiamberardinoM.A. Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis.Pain20161571809110.1097/j.pain.000000000000022025974242
     [Google Scholar]
  64. SkaperS.D. FacciL. GiustiP. Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator.Mol. Neurobiol.201348234035210.1007/s12035‑013‑8487‑623813098
     [Google Scholar]
  65. PetrosinoS. Schiano MorielloA. VerdeR. AllaràM. ImperatoreR. LigrestiA. MahmoudA.M. PeritoreA.F. IannottiF.A. Di MarzoV. Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity.J. Neuroinflammation201916127410.1186/s12974‑019‑1671‑531878942
     [Google Scholar]
  66. ZuoY. PerkinsN.M. TraceyD.J. GeczyC.L. Inflammation and hyperalgesia induced by nerve injury in the rat: A key role of mast cells.Pain2003105346747910.1016/S0304‑3959(03)00261‑614527707
     [Google Scholar]
  67. SmithF.M. HaskelbergH. TraceyD.J. Moalem-TaylorG. Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury.Neuroimmunomodulation200714631732510.1159/00012504818401194
     [Google Scholar]
  68. ObaraI. TelezhkinV. AlrashdiI. ChazotP.L. Histamine, histamine receptors, and neuropathic pain relief.Br. J. Pharmacol.2020177358059910.1111/bph.1469631046146
     [Google Scholar]
  69. AbramoF. LazzariniG. PironeA. LenziC. AlbertiniS. della ValleM.F. SchievanoC. VannozziI. MiragliottaV. Ultramicronized palmitoylethanolamide counteracts the effects of compound 48/80 in a canine skin organ culture model.Vet. Dermatol.2017285456e10410.1111/vde.1245628585337
     [Google Scholar]
  70. CerratoS. BrazisP. della ValleM.F. MioloA. PuigdemontA. Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFα release from canine skin mast cells.Vet. Immunol. Immunopathol.2010133191510.1016/j.vetimm.2009.06.01119625089
     [Google Scholar]
  71. SchweigerV. MartiniA. BellamoliP. DonadelloK. SchievanoC. BalzoG.D. Sarzi-PuttiniP. ParoliniM. PolatiE. Ultramicronized palmitoylethanolamide (um-PEA) as add-on treatment in fibromyalgia syndrome (FMS): Retrospective observational study on 407 patients.CNS Neurol. Disord. Drug Targets201918432633310.2174/187152731866619022720535930827269
     [Google Scholar]
  72. PapettiL. SforzaG. TulloG. Alaimo di LoroP. MoaveroR. UrsittiF. FerilliM.A.N. TarantinoS. VigevanoF. ValerianiM. Tolerability of palmitoylethanolamide in a pediatric population suffering from migraine: A pilot study.Pain Res. Manag.202020201710.1155/2020/393864032377286
     [Google Scholar]
  73. CruccuG. StefanoG.D. MarchettiniP. TruiniA. Micronized palmitoylethanolamide: A post hoc analysis of a controlled study in patients with low back pain - sciatica.CNS Neurol. Disord. Drug Targets201918649149510.2174/187152731866619070311003631269891
     [Google Scholar]
  74. ScaturroD. AsaroC. LauricellaL. TomaselloS. VarrassiG. Letizia MauroG. Combination of rehabilitative therapy with ultramicronized palmitoylethanolamide for chronic low back pain: An observational study.Pain Ther.20209131932610.1007/s40122‑019‑00140‑931863365
     [Google Scholar]
/content/journals/cn/10.2174/1570159X21666221128091453
Loading
Ultramicronized N-palmitoylethanolamine Contributes to Morphine Efficacy Against Neuropathic Pain: Implication of Mast Cells and Glia
Curr. Neuropharmacol. 22, 88 (2024); https://doi.org/10.2174/1570159X21666221128091453
/content/journals/cn/10.2174/1570159X21666221128091453
/content/journals/cn/10.2174/1570159X21666221128091453
Loading

Data & Media loading...

Supplements

Supplementary Material

file format download
  • Article Type: Research Article
Keyword(s): glia; histamine; mast cell; morphine; neuropathic pain; opioid; Ultramicronized N-palmitoylethanolamine (PEA)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test