Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Neuropathic Pain in Aged People: An Unresolved Issue Open to Novel Drug Approaches, Focusing on Painful Diabetic Neuropathy

Author(s): Nicoletta Marchesi*, Foroogh Fahmideh, Alessia Pascale, Massimo Allegri and Stefano Govoni

Volume 22, Issue 1, 2024

Published on: 07 August, 2023

Page: [53 - 64] Pages: 12

DOI: 10.2174/1570159X21666230807103642

Price: $65

Abstract

A majority of older patients suffer from neuropathic pain (NP) that significantly alters their daily activities and imposes a significant burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it challenging to determine the appropriate drug, dosage, and maintenance of therapy. Age-dependent processes play a contributing role in neuropathy given that diabetic neuropathy (DN) is the most common form of neuropathy. This narrative review is mainly focused on the drug treatment approach for neuropathy-associated pain in aged people including both drugs and dietary supplements, considering the latter as add-on mechanism-based treatments to increase the effectiveness of usual treatments by implementing their activity or activating other analgesic pathways. On one hand, the limited clinical studies assessing the effectiveness and the adverse effects of existing pain management options in this age segment of the population (> 65), on the other hand, the expanding global demographics of the elderly contribute to building up an unresolved pain management problem that needs the attention of healthcare providers, researchers, and health authorities as well as the expansion of the current therapeutic options.

Graphical Abstract

[1]
Finnerup, N.B.; Attal, N.; Haroutounian, S.; McNicol, E.; Baron, R.; Dworkin, R.H.; Gilron, I.; Haanpää, M.; Hansson, P.; Jensen, T.S.; Kamerman, P.R.; Lund, K.; Moore, A.; Raja, S.N.; Rice, A.S.C.; Rowbotham, M.; Sena, E.; Siddall, P.; Smith, B.H.; Wallace, M. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol., 2015, 14(2), 162-173.
[http://dx.doi.org/10.1016/S1474-4422(14)70251-0] [PMID: 25575710]
[2]
Allegri, N.; Mennuni, S.; Rulli, E.; Vanacore, N.; Corli, O.; Floriani, I. Systematic review and meta-analysis on neuropsychological effects of long-term use of opioids in patients with chronic noncancer pain. Pain Pract., 2018, 19(3), 328-343.
[http://dx.doi.org/10.1111/papr.12741]
[3]
Tsai, Y.I.; Browne, G.; Inder, K.J. Nurses’ perspectives of pain assessment and management in dementia care in hospital. Australas. J. Ageing, 2023, 42(2), 382-391.
[http://dx.doi.org/10.1111/ajag.13146]
[4]
Tsai, Y.I.P.; Browne, G.; Inder, K.J. The effectiveness of interventions to improve pain assessment and management in people living with dementia: A systematic review and meta‐analyses. J. Adv. Nurs., 2021, 77(3), 1127-1140.
[http://dx.doi.org/10.1111/jan.14660] [PMID: 33222273]
[5]
Colloca, L.; Ludman, T.; Bouhassira, D.; Baron, R.; Dickenson, A.H.; Yarnitsky, D.; Freeman, R.; Truini, A.; Attal, N.; Finnerup, N.B.; Eccleston, C.; Kalso, E.; Bennett, D.L.; Dworkin, R.H.; Raja, S.N. Neuropathic pain. Nat. Rev. Dis. Primers, 2017, 3(1), 17002.
[http://dx.doi.org/10.1038/nrdp.2017.2] [PMID: 28205574]
[6]
Kandil, A.; Perret, D. Classification of Neuropathic Pain. In: Neuropathic Pain; Oxford University Press: Oxford, UK, 2018; pp. 11-16.
[http://dx.doi.org/10.1093/med/9780190298357.003.0002]
[7]
Giovannini, S.; Coraci, D.; Brau, F.; Galluzzo, V.; Loreti, C.; Caliandro, P.; Padua, L.; Maccauro, G.; Biscotti, L.; Bernabei, R. Neuropathic pain in the elderly. Diagnostics, 2021, 11(4), 613.
[http://dx.doi.org/10.3390/diagnostics11040613] [PMID: 33808121]
[8]
Salman, R.R.; Delbari, A.; Asadi-Lari, M.; Rashedi, V.; Lökk, J. Neuropathic pain prevalence of older adults in an urban area of Iran: A population-based study. Pain Res. Treat., 2019, 2019, 1-8.
[http://dx.doi.org/10.1155/2019/9015695] [PMID: 30719350]
[9]
Stompór, M.; Grodzicki, T.; Stompór, T.; Wordliczek, J.; Dubiel, M.; Kurowska, I. Prevalence of chronic pain, particularly with neuropathic component, and its effect on overall functioning of elderly patients. Med. Sci. Monit., 2019, 25, 2695-2701.
[http://dx.doi.org/10.12659/MSM.911260] [PMID: 31018630]
[10]
van Hecke, O.; Austin, S.K.; Khan, R.A.; Smith, B.H.; Torrance, N. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain, 2014, 155(4), 654-662.
[http://dx.doi.org/10.1016/j.pain.2013.11.013] [PMID: 24291734]
[11]
Loeser, J.D.; Treede, R.D. The kyoto protocol of IASP basic pain terminology. Pain, 2008, 137(3), 473-477.
[http://dx.doi.org/10.1016/j.pain.2008.04.025] [PMID: 18583048]
[12]
Wood, M. Understanding pain in herpes zoster: An essential for optimizing treatment. J. Infect. Dis., 2002, 186(S1), S78-S82.
[http://dx.doi.org/10.1086/342958] [PMID: 12353191]
[13]
Kieseier, B.C.; Mathey, E.K.; Sommer, C.; Hartung, H.P. Immune-mediated neuropathies. Nat. Rev. Dis. Primers, 2018, 4(1), 31.
[http://dx.doi.org/10.1038/s41572-018-0027-2] [PMID: 30310069]
[14]
Belmin, J.; Valensi, P. Diabetic neuropathy in elderly patients. What can be done? Drugs Aging, 1996, 8(6), 416-429.
[http://dx.doi.org/10.2165/00002512-199608060-00003] [PMID: 8736625]
[15]
Vinik, A.I.; Strotmeyer, E.S.; Nakave, A.A.; Patel, C.V. Diabetic neuropathy in older adults. Clin. Geriatr. Med., 2008, 24(3), 407-435. v.
[http://dx.doi.org/10.1016/j.cger.2008.03.011] [PMID: 18672180]
[16]
Pop-Busui, R.; Boulton, A.J.M.; Feldman, E.L.; Bril, V.; Freeman, R.; Malik, R.A.; Sosenko, J.M.; Ziegler, D. Diabetic neuropathy: A position statement by the american diabetes association. Diabetes Care, 2017, 40(1), 136-154.
[http://dx.doi.org/10.2337/dc16-2042] [PMID: 27999003]
[17]
Pfannkuche, A.; Alhajjar, A.; Ming, A.; Walter, I.; Piehler, C.; Mertens, P.R. Prevalence and risk factors of diabetic peripheral neuropathy in a diabetics cohort: Register initiative diabetes and nerves. End. Metabol. Sci., 2020, 1(1-2), 100053.
[http://dx.doi.org/10.1016/j.endmts.2020.100053]
[18]
Davies, M.; Brophy, S.; Williams, R.; Taylor, A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care, 2006, 29(7), 1518-1522.
[http://dx.doi.org/10.2337/dc05-2228] [PMID: 16801572]
[19]
Dyck, P.J.; Kratz, K.M.; Karnes, J.L.; Litchy, W.J.; Klein, R.; Pach, J.M.; Wilson, D.M.; O’Brien, P.C.; Melton, L.J., III; Service, F.J. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: The Rochester Diabetic Neuropathy Study. Neurology, 1993, 43(4), 817-824.
[http://dx.doi.org/10.1212/WNL.43.4.817] [PMID: 8469345]
[20]
Simo, N.; Kuate-Tegueu, C.; Ngankou-Tchankeu, S.; Doumbe, J.; Maiga, Y.; Cesari, M.; Dartigues, J.F.; Kengne, A.P.; Tabue-Teguo, M. Correlates of diabetic polyneuropathy of the elderly in Sub-Saharan Africa. PLoS One, 2020, 15(10), e0240602.
[http://dx.doi.org/10.1371/journal.pone.0240602] [PMID: 33119646]
[21]
Baderca, F.; Timar, B.; Popescu, S.; Simu, M.; Diaconu, L.; Velea, I.; Timar, R. Age as an independent factor for the development of neuropathy in diabetic patients. Clin. Interv. Aging, 2016, 11, 313.
[http://dx.doi.org/10.2147/CIA.S97295]
[22]
Poliakov, I.; Toth, C. The impact of pain in patients with polyneuropathy. Eur. J. Pain, 2011, 15(10), 1015-1022.
[http://dx.doi.org/10.1016/j.ejpain.2011.04.013] [PMID: 21600817]
[23]
Tracy, B.; Sean Morrison, R. Pain management in older adults. Clin. Ther., 2013, 35(11), 1659-1668.
[http://dx.doi.org/10.1016/j.clinthera.2013.09.026] [PMID: 24148553]
[24]
Defrin, R.; Amanzio, M.; de Tommaso, M.; Dimova, V.; Filipovic, S.; Finn, D.P.; Gimenez-Llort, L.; Invitto, S.; Jensen-Dahm, C.; Lautenbacher, S.; Oosterman, J.M.; Petrini, L.; Pick, C.G.; Pickering, G.; Vase, L.; Kunz, M. Experimental pain processing in individuals with cognitive impairment. Pain, 2015, 156(8), 1396-1408.
[http://dx.doi.org/10.1097/j.pain.0000000000000195] [PMID: 26181216]
[25]
Hicks, C.W.; Selvin, E. Epidemiology of peripheral neuropathy and lower extremity disease in diabetes. Curr. Diab. Rep., 2019, 19(10), 86.
[http://dx.doi.org/10.1007/s11892-019-1212-8] [PMID: 31456118]
[26]
Giovannini, S.; Onder, G.; Leeuwenburgh, C.; Carter, C.; Marzetti, E.; Russo, A.; Capoluongo, E.; Pahor, M.; Bernabei, R.; Landi, F. Myeloperoxidase levels and mortality in frail community-living elderly individuals. J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65A(4), 369-376.
[http://dx.doi.org/10.1093/gerona/glp183] [PMID: 20064836]
[27]
Edwards, J.L.; Vincent, A.M.; Cheng, H.T.; Feldman, E.L. Diabetic neuropathy: Mechanisms to management. Pharmacol. Ther., 2008, 120(1), 1-34.
[http://dx.doi.org/10.1016/j.pharmthera.2008.05.005] [PMID: 18616962]
[28]
Pop-Busui, R.; Sima, A.; Stevens, M. Diabetic neuropathy and oxidative stress. Diabetes Metab. Res. Rev., 2006, 22(4), 257-273.
[http://dx.doi.org/10.1002/dmrr.625] [PMID: 16506271]
[29]
Bruunsgaard, H.; Pedersen, M.; Pedersen, B.K. Aging and proinflammatory cytokines. Curr. Opin. Hematol., 2001, 8(3), 131-136.
[http://dx.doi.org/10.1097/00062752-200105000-00001] [PMID: 11303144]
[30]
Takeshita, Y.; Sato, R.; Kanda, T. Blood-Nerve Barrier (BNB) pathology in diabetic peripheral neuropathy and in vitro human BNB model. Int. J. Mol. Sci., 2020, 22(1), 62.
[http://dx.doi.org/10.3390/ijms22010062] [PMID: 33374622]
[31]
Xu, X.; Wang, B.; Ren, C.; Hu, J.; Greenberg, D.A.; Chen, T.; Xie, L.; Jin, K. Age-related impairment of vascular structure and functions. Aging Dis., 2017, 8(5), 590-610.
[http://dx.doi.org/10.14336/AD.2017.0430] [PMID: 28966804]
[32]
Jaruchart, T.; Suwanwela, N.C.; Tanaka, H.; Suksom, D. Arterial stiffness is associated with age-related differences in cerebrovascular conductance. Exp. Gerontol., 2016, 73, 59-64.
[http://dx.doi.org/10.1016/j.exger.2015.11.006] [PMID: 26571202]
[33]
Perucca, E.; Berlowitz, D.; Birnbaum, A.; Cloyd, J.C.; Garrard, J.; Hanlon, J.T.; Levy, R.H.; Pugh, M.J. Pharmacological and clinical aspects of antiepileptic drug use in the elderly. Epilepsy Res., 2006, 68(Suppl. 1), 49-63.
[http://dx.doi.org/10.1016/j.eplepsyres.2005.07.017] [PMID: 16207524]
[34]
Cusack, B.J. Pharmacokinetics in older persons. Am. J. Geriatr. Pharmacother., 2004, 2(4), 274-302.
[http://dx.doi.org/10.1016/j.amjopharm.2004.12.005] [PMID: 15903286]
[35]
Burris, J.E. Pharmacologic approaches to geriatric pain management11No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors(s) or upon any organization with which the author(s) is/are associated. Arch. Phys. Med. Rehabil., 2004, 85(7)(Suppl. 3), 45-49.
[http://dx.doi.org/10.1016/j.apmr.2004.03.011] [PMID: 15221725]
[36]
Pharmacodynamics in Older Adults - Geriatrics. MSD Manual Professional Edition. Available from: https://www.msdmanuals.com/professional/geriatrics/drug-therapy-in-older-adults/pharmacodynamics-in-older-adults
[37]
Bates, D.; Schultheis, B.C.; Hanes, M.C.; Jolly, S.M.; Chakravarthy, K.V.; Deer, T.R.; Levy, R.M.; Hunter, C.W. A Comprehensive algorithm for management of neuropathic pain. Pain Med., 2019, 20(Suppl. 1), S2-S12.
[http://dx.doi.org/10.1093/pm/pnz075] [PMID: 31152178]
[38]
Semel, D.; Murphy, T.K.; Zlateva, G.; Cheung, R.; Emir, B. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies. BMC Fam. Pract., 2010, 11(1), 85.
[http://dx.doi.org/10.1186/1471-2296-11-85] [PMID: 21054853]
[39]
Dallocchio, C.; Buffa, C.; Mazzarello, P.; Chiroli, S. Gabapentin vs. amitriptyline in painful diabetic neuropathy: An open-label pilot study. J. Pain Symptom Manage., 2000, 20(4), 280-285.
[http://dx.doi.org/10.1016/S0885-3924(00)00181-0] [PMID: 11027910]
[40]
Boyle, J.; Eriksson, M.E.V.; Gribble, L.; Gouni, R.; Johnsen, S.; Coppini, D.V.; Kerr, D. Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care, 2012, 35(12), 2451-2458.
[http://dx.doi.org/10.2337/dc12-0656] [PMID: 22991449]
[41]
Watson, P.C.N.; Moulin, D.; Watt-Watson, J.; Gordon, A.; Eisenhoffer, J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain, 2003, 105(1), 71-78.
[http://dx.doi.org/10.1016/S0304-3959(03)00160-X] [PMID: 14499422]
[42]
Wasan, A.; Ossanna, M.; Raskin, J.; Wernicke, J.; Robinson, M.; Hall, J.; Edwards, S.; Lipsius, S.; Meyers, A.; McCarberg, B. Safety and efficacy of duloxetine in the treatment of diabetic peripheral neuropathic pain in older patients. Curr. Drug Saf., 2009, 4(1), 22-29.
[http://dx.doi.org/10.2174/157488609787354404] [PMID: 19149522]
[43]
Cruccu, G.; Truini, A. A review of neuropathic pain: from guidelines to clinical practice. Pain Ther., 2017, 6(Suppl. 1), 35-42.
[http://dx.doi.org/10.1007/s40122-017-0087-0] [PMID: 29178033]
[44]
Ferrell, B.A. Pain Management. In: Hazzard’s Geriatric Medicine and Gerontology; 7th ed; Halter, J.B.; Ouslander, J.G.; Studenski, S.; High, K.P.; Asthana, S.; Supiano, M.A., Eds.; McGraw-Hill Education: New York, 2017.
[45]
Nicholson, B.; Verma, S. Comorbidities in chronic neuropathic pain. Pain Med., 2004, 5(Suppl. 1), S9-S27.
[http://dx.doi.org/10.1111/j.1526-4637.2004.04019.x] [PMID: 14996227]
[46]
Gallagher, R.; Apostle, N. Peripheral edema with pregabalin. CMAJ, 2013, 185(10), E506-E506.
[http://dx.doi.org/10.1503/cmaj.121232] [PMID: 23128284]
[47]
Azmi, S.; ElHadd, K.T.; Nelson, A.; Chapman, A.; Bowling, F.L.; Perumbalath, A.; Lim, J.; Marshall, A.; Malik, R.A.; Alam, U. Pregabalin in the management of painful diabetic neuropathy: a narrative review. Diabetes Ther., 2019, 10(1), 35-56.
[http://dx.doi.org/10.1007/s13300-018-0550-x] [PMID: 30565054]
[48]
Usmani, H.; Amir, S.H.; Nasreen, F.; Siddiqi, S.; Hasan, M.; Tauheed, N. Pregabalin versus oxcarbazepine in painful diabetic neuropathy in elderly population: Efficacy and safety in terms of pain relief, cognitive function, and overall quality of life. Indian J. Pain, 2018, 32(1), 40.
[http://dx.doi.org/10.4103/ijpn.ijpn_76_17]
[49]
Nasreddine, W.; Beydoun, A. Oxcarbazepine in neuropathic pain. Expert Opin. Investig. Drugs, 2007, 16(10), 1615-1625.
[http://dx.doi.org/10.1517/13543784.16.10.1615] [PMID: 17922625]
[50]
Gilron, I.; Bailey, J.M.; Tu, D.; Holden, R.R.; Jackson, A.C.; Houlden, R.L. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet, 2009, 374(9697), 1252-1261.
[http://dx.doi.org/10.1016/S0140-6736(09)61081-3] [PMID: 19796802]
[51]
Rowbotham, M.C.; Goli, V.; Kunz, N.R.; Lei, D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain, 2004, 110(3), 697-706.
[http://dx.doi.org/10.1016/j.pain.2004.05.010] [PMID: 15288411]
[52]
Aiyer, R.; Barkin, R.L.; Bhatia, A. Treatment of neuropathic pain with venlafaxine: A systematic review. Pain Med., 2017, 18(10), 1999-2012.
[http://dx.doi.org/10.1093/pm/pnw261] [PMID: 27837032]
[53]
Cheng, C.W.H.; Wong, C.S.M.; Hui, G.K.M.; Chung, E.K.N.; Wong, S.H.S. Fibromyalgia: is it a neuropathic pain? Pain Manag. (Lond.), 2018, 8(5), 377-388.
[http://dx.doi.org/10.2217/pmt-2018-0024] [PMID: 30212264]
[54]
Datta Gupta, A.; Edwards, S.; Smith, J.; Snow, J.; Visvanathan, R.; Tucker, G.; Wilson, D. A Systematic review and meta-analysis of efficacy of botulinum toxin a for neuropathic Pain. Toxins, 2022, 14(1), 36.
[http://dx.doi.org/10.3390/toxins14010036] [PMID: 35051013]
[55]
Egeo, G.; Fofi, L.; Barbanti, P. Botulinum neurotoxin for the treatment of neuropathic pain. Front. Neurol., 2020, 11, 716.
[http://dx.doi.org/10.3389/fneur.2020.00716] [PMID: 32849195]
[56]
Didangelos, T.; Karlafti, E.; Kotzakioulafi, E.; Margariti, E.; Giannoulaki, P.; Batanis, G.; Tesfaye, S.; Kantartzis, K. Vitamin B12 supplementation in diabetic neuropathy: A 1-year, randomized, double-blind, placebo-controlled trial. Nutrients, 2021, 13(2), 395.
[http://dx.doi.org/10.3390/nu13020395] [PMID: 33513879]
[57]
Miller, J.W. Proton pump inhibitors, H2-receptor antagonists, metformin, and vitamin B12 deficiency: clinical implications. Adv. Nutr., 2018, 9(4), 511S-518S.
[http://dx.doi.org/10.1093/advances/nmy023] [PMID: 30032223]
[58]
Alvarez, M.; Sierra, O.R.; Saavedra, G.; Moreno, S. Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: A cross-sectional study. Endocr. Connect., 2019, 8(10), 1324-1329.
[http://dx.doi.org/10.1530/EC-19-0382] [PMID: 31518991]
[59]
Putz, Z.; Tordai, D.; Hajdú, N.; Vági, O.E.; Kempler, M.; Békeffy, M.; Körei, A.E.; Istenes, I.; Horváth, V.; Stoian, A.P.; Rizzo, M.; Papanas, N.; Kempler, P. Vitamin D in the prevention and treatment of diabetic neuropathy. Clin. Ther., 2022, 44(5), 813-823.
[http://dx.doi.org/10.1016/j.clinthera.2022.03.012] [PMID: 35428527]
[60]
Putz, Z.; Martos, T.; Németh, N.; Körei, A.E.; Vági, O.E.; Kempler, M.S.; Kempler, P. Is there an association between diabetic neuropathy and low vitamin D levels? Curr. Diab. Rep., 2014, 14(10), 537.
[http://dx.doi.org/10.1007/s11892-014-0537-6] [PMID: 25142719]
[61]
Garcion, E.; Wion-Barbot, N.; Montero-Menei, C.N.; Berger, F.; Wion, D. New clues about vitamin D functions in the nervous system. Trends Endocrinol. Metab., 2002, 13(3), 100-105.
[http://dx.doi.org/10.1016/S1043-2760(01)00547-1] [PMID: 11893522]
[62]
Zhang, Y.; Gong, S.; He, L.; Zhou, M.; Guo, J.; Hoke, A.; Zhu, C. Nerve growth factor for neuropathic pain. Cochrane Libr., 2017, 2017(11), CDD12800.
[http://dx.doi.org/10.1002/14651858.CD012800]
[63]
Khan, N.; Smith, M. Neurotrophins and neuropathic pain: role in pathobiology. Molecules, 2015, 20(6), 10657-10688.
[http://dx.doi.org/10.3390/molecules200610657] [PMID: 26065639]
[64]
McArthur, J.C.; Yiannoutsos, C.; Simpson, D.M.; Adornato, B.T.; Singer, E.J.; Hollander, H.; Marra, C.; Rubin, M.; Cohen, B.A.; Tucker, T.; Navia, B.A.; Schifitto, G.; Katzenstein, D.; Rask, C.; Zaborski, L.; Smith, M.E.; Shriver, S.; Millar, L.; Clifford, D.B.; Karalnik, I.J. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology, 2000, 54(5), 1080-1088.
[http://dx.doi.org/10.1212/WNL.54.5.1080] [PMID: 10720278]
[65]
Riaz, S.; Malcangio, M.; Miller, M.; Tomlinson, D.R. A vitamin D 3 derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats. Diabetologia, 1999, 42(11), 1308-1313.
[http://dx.doi.org/10.1007/s001250051443] [PMID: 10550414]
[66]
Llewellyn, D.J.; Lang, I.A.; Langa, K.M.; Muniz-Terrera, G.; Phillips, C.L.; Cherubini, A.; Ferrucci, L.; Melzer, D. Vitamin D and risk of cognitive decline in elderly persons. Arch. Intern. Med., 2010, 170(13), 1135-1141.
[http://dx.doi.org/10.1001/archinternmed.2010.173] [PMID: 20625021]
[67]
Wion, D.; Macgrogan, D.; Neveu, I.; Jehan, F.; Houlgatte, R.; Brachet, P. 1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. J. Neurosci. Res., 1991, 28(1), 110-114.
[http://dx.doi.org/10.1002/jnr.490280111] [PMID: 1904101]
[68]
Cornet, A.; Baudet, C.; Neveu, I.; Baron-Van Evercooren, A.; Brachet, P.; Naveilhan, P. 1,25‐dihydroxyvitamin D3 regulates the expression of VDR and NGF gene in Schwann cells in vitro. J. Neurosci. Res., 1998, 53(6), 742-746.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19980915)53:6<742:AID-JNR11>3.0.CO;2-#] [PMID: 9753201]
[69]
Saporito, M.S.; Brown, E.R.; Hartpence, K.C.; Wilcox, H.M.; Vaught, J.L.; Carswell, S. Chronic 1,25-dihydroxyvitamin D3-mediated induction of nerve growth factor mRNA and protein in L929 fibroblasts and in adult rat brain. Brain Res., 1994, 633(1-2), 189-196.
[http://dx.doi.org/10.1016/0006-8993(94)91539-3] [PMID: 8137156]
[70]
Naveilhan, P.; Neveu, I.; Wion, D.; Brachet, P. 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport, 1996, 7(13), 2171-2175.
[http://dx.doi.org/10.1097/00001756-199609020-00023] [PMID: 8930983]
[71]
Neveu, I.; Naveilhan, P.; Baudet, C.; Brachet, P.; Metsis, M. 1,25-Dihydroxyvitamin D3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport, 1994, 6(1), 124-126.
[http://dx.doi.org/10.1097/00001756-199412300-00032] [PMID: 7703399]
[72]
Wang, J.Y.; Wu, J.N.; Cherng, T.L.; Hoffer, B.J.; Chen, H.H.; Borlongan, C.V.; Wang, Y. Vitamin D3 attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res., 2001, 904(1), 67-75.
[http://dx.doi.org/10.1016/S0006-8993(01)02450-7] [PMID: 11516412]
[73]
El Soury, M.; Fornasari, B.E.; Carta, G.; Zen, F.; Haastert-Talini, K.; Ronchi, G. The role of dietary nutrients in peripheral nerve regeneration. Int. J. Mol. Sci., 2021, 22(14), 7417.
[http://dx.doi.org/10.3390/ijms22147417] [PMID: 34299037]
[74]
Gao, Z.; Feng, Y.; Ju, H. The different dynamic changes of nerve growth factor in the dorsal horn and dorsal root ganglion leads to hyperalgesia and allodynia in diabetic neuropathic pain. Pain Physician, 2017, 20(4), E551-E561.
[PMID: 28535564]
[75]
Lee, P.; Chen, R. Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch. Intern. Med., 2008, 168(7), 771-772.
[http://dx.doi.org/10.1001/archinte.168.7.771] [PMID: 18413561]
[76]
Alam, U.; Najam, O.; Al-Himdani, S.; Benoliel, S.; Jinadev, P.; Berry, J.L.; Kew, M.; Asghar, O.; Petropoulos, I.N.; Malik, R.A. Marked vitamin D deficiency in patients with diabetes in the UK: ethnic and seasonal differences and an association with dyslipidaemia. Diabet. Med., 2012, 29(10), 1343-1345.
[http://dx.doi.org/10.1111/j.1464-5491.2012.03692.x] [PMID: 22507464]
[77]
Ghadiri-Anari, A.; Mozafari, Z.; Gholami, S.; Khodaei, S.A.; Aboutorabi-zarchi, M.; Sepehri, F.; Nadjarzade, A.; Rahmanian, M.; Namiranian, N. Dose vitamin D supplementations improve peripheral diabetic neuropathy? A before-after clinical trial. Diabetes Metab. Syndr., 2019, 13(1), 890-893.
[http://dx.doi.org/10.1016/j.dsx.2018.12.014] [PMID: 30641826]
[78]
Xiaohua, G.; Dongdong, L.; Xiaoting, N.; Shuoping, C.; Feixia, S.; Huajun, Y.; Qi, Z.; Zimiao, C. Severe vitamin D deficiency is associated with increased expression of inflammatory cytokines in painful diabetic peripheral neuropathy. Front. Nutr., 2021, 8, 612068.
[http://dx.doi.org/10.3389/fnut.2021.612068] [PMID: 33777989]
[79]
Kweder, H.; Eidi, H. Vitamin D deficiency in elderly: Risk factors and drugs impact on vitamin D status. Avicenna J. Med., 2018, 8(4), 139-146.
[http://dx.doi.org/10.4103/ajm.AJM_20_18] [PMID: 30319955]
[80]
Yammine, K.; Wehbe, R.; Assi, C. A systematic review on the efficacy of vitamin D supplementation on diabetic peripheral neuropathy. Clin. Nutr., 2020, 39(10), 2970-2974.
[http://dx.doi.org/10.1016/j.clnu.2020.01.022] [PMID: 32089370]
[81]
Marchesi, N.; Govoni, S.; Allegri, M. Non‐drug pain relievers active on non‐opioid pain mechanisms. Pain Pract., 2022, 22(2), 255-275.
[http://dx.doi.org/10.1111/papr.13073] [PMID: 34498362]
[82]
Hakimizad, R.; Soltani, R.; Khorvash, F.; Marjani, M.; Dastan, F. The effect of acetyl-L-carnitine, alpha-lipoic acid, and coenzyme Q10 combination in preventing anti-tuberculosis drug-induced hepatotoxicity: a randomized, double-blind, placebo-controlled clinical trial. Iran. J. Pharm. Res., 2021, 20(3), 431-440.
[http://dx.doi.org/10.22037/ijpr.2021.114618.14953] [PMID: 34903999]
[83]
Colucci, W.J.; Gandour, R.D. Carnitine acetyltransferase: A review of its biology, enzymology, and bioorganic chemistry. Bioorg. Chem., 1988, 16(3), 307-334.
[http://dx.doi.org/10.1016/0045-2068(88)90018-1]
[84]
Virmani, M.A.; Biselli, R.; Spadoni, A.; Rossi, S.; Corsico, N.; Calvani, M.; Fattorossi, A.; De Simone, C.; Arrigoni-Martelli, E. Protective actions of l-carnitine and acetyl-l-carnitine on the neurotoxicity evoked by mitochondrial uncoupling or inhibitors. Pharmacol. Res., 1995, 32(6), 383-389.
[http://dx.doi.org/10.1016/S1043-6618(05)80044-1] [PMID: 8736490]
[85]
Sima, A.A.; Ristic, H.; Merry, A.; Kamijo, M.; Lattimer, S.A.; Stevens, M.J.; Greene, D.A. Primary preventive and secondary interventionary effects of acetyl-L-carnitine on diabetic neuropathy in the bio-breeding Worcester rat. J. Clin. Invest., 1996, 97(8), 1900-1907.
[http://dx.doi.org/10.1172/JCI118621] [PMID: 8621774]
[86]
Hart, A.M.; Wiberg, M.; Youle, M.; Terenghi, G. Systemic acetyl-l-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma. Exp. Brain Res., 2002, 145(2), 182-189.
[http://dx.doi.org/10.1007/s00221-002-1100-2] [PMID: 12110958]
[87]
Di Cesare Mannelli, L.; Ghelardini, C.; Calvani, M.; Nicolai, R.; Mosconi, L.; Vivoli, E.; Pacini, A.; Bartolini, A. Protective effect of acetyl-l-carnitine on the apoptotic pathway of peripheral neuropathy. Eur. J. Neurosci., 2007, 26(4), 820-827.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05722.x] [PMID: 17714181]
[88]
De Grandis, D.; Minardi, C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D., 2002, 3(4), 223-231.
[http://dx.doi.org/10.2165/00126839-200203040-00001] [PMID: 12455197]
[89]
Sima, A.A.F.; Calvani, M.; Mehra, M.; Amato, A. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy. Diabetes Care, 2005, 28(1), 89-94.
[http://dx.doi.org/10.2337/diacare.28.1.89] [PMID: 15616239]
[90]
Li, S.; Chen, X.; Li, Q.; Du, J.; Liu, Z.; Peng, Y.; Xu, M.; Li, Q.; Lei, M.; Wang, C.; Zheng, S.; Zhang, X.; Yu, H.; Shi, J.; Tao, S.; Feng, P.; Tian, H. Effects of acetyl‐L‐carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double‐blind, controlled trial. J. Diabetes Investig., 2016, 7(5), 777-785.
[http://dx.doi.org/10.1111/jdi.12493] [PMID: 27180954]
[91]
Rolim, L.C.S.P.; da Silva, E.M.K.; Flumignan, R.L.G.; Abreu, M.M.; Dib, S.A. Acetyl-L-carnitine for the treatment of diabetic peripheral neuropathy. Cochrane Libr., 2019, 2019(6), CD011265.
[http://dx.doi.org/10.1002/14651858.CD011265.pub2] [PMID: 31201734]
[92]
Catania, V.E.; Malaguarnera, G.; Bertino, G.; Chisari, L.M.; Castorina, M.; Bonfiglio, C.; Cauli, O.; Malaguarnera, M. Acetyl-L-carnitine can slow the progression from prefrailty to frailty in older subjects. A randomized interventional clinical trial. Curr. Pharm. Des., 2022, 28(38), 3158-3166.
[http://dx.doi.org/10.2174/1381612828666220830092815] [PMID: 36043711]
[93]
Ziegler, D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat. Endocrinol., 2004, 3(3), 173-189.
[http://dx.doi.org/10.2165/00024677-200403030-00005] [PMID: 16026113]
[94]
Mijnhout, G.S.; Kollen, B.J.; Alkhalaf, A.; Kleefstra, N.; Bilo, H.J.G. Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int. J. Endocrinol., 2012, 2012, 1-8.
[http://dx.doi.org/10.1155/2012/456279] [PMID: 22331979]
[95]
Han, T.; Bai, J.; Liu, W.; Hu, Y. Therapy of endocrine disease: A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur. J. Endocrinol., 2012, 167(4), 465-471.
[http://dx.doi.org/10.1530/EJE-12-0555] [PMID: 22837391]
[96]
Elbadawy, A.M.; Abd Elmoniem, R.O.; Elsayed, A.M. Alpha lipoic acid and diabetes mellitus: potential effects on peripheral neuropathy and different metabolic parameters. Alex. J. Med., 2021, 57(1), 113-120.
[http://dx.doi.org/10.1080/20905068.2021.1907961]
[97]
Agathos, E.; Tentolouris, A.; Eleftheriadou, I.; Katsaouni, P.; Nemtzas, I.; Petrou, A.; Papanikolaou, C.; Tentolouris, N. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J. Int. Med. Res., 2018, 46(5), 1779-1790.
[http://dx.doi.org/10.1177/0300060518756540] [PMID: 29517942]
[98]
Fattori, V.; Hohmann, M.; Rossaneis, A.; Pinho-Ribeiro, F.; Verri, W. Capsaicin: current understanding of its mechanisms and therapy of pain and other pre-clinical and clinical uses. Molecules, 2016, 21(7), 844.
[http://dx.doi.org/10.3390/molecules21070844] [PMID: 27367653]
[99]
Chung, M.K.; Campbell, J. Use of capsaicin to treat pain: mechanistic and therapeutic considerations. Pharmaceuticals (Basel), 2016, 9(4), 66.
[http://dx.doi.org/10.3390/ph9040066] [PMID: 27809268]
[100]
Baranidharan, G.; Das, S.; Bhaskar, A. A review of the high-concentration capsaicin patch and experience in its use in the management of neuropathic pain. Ther. Adv. Neurol. Disord., 2013, 6(5), 287-297.
[http://dx.doi.org/10.1177/1756285613496862] [PMID: 23997814]
[101]
Epstein, J.B.; Marcoe, J.H. Topical application of capsaicin for treatment of oral neuropathic pain and trigeminal neuralgia. Oral Surg. Oral Med. Oral Pathol., 1994, 77(2), 135-140.
[http://dx.doi.org/10.1016/0030-4220(94)90275-5] [PMID: 8139830]
[102]
Campbell, C.M.; Kipnes, M.S.; Stouch, B.C.; Brady, K.L.; Kelly, M.; Schmidt, W.K.; Petersen, K.L.; Rowbotham, M.C.; Campbell, J.N. Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy. Pain, 2012, 153(9), 1815-1823.
[http://dx.doi.org/10.1016/j.pain.2012.04.014] [PMID: 22683276]
[103]
Mankowski, C.; Poole, C.D.; Ernault, E.; Thomas, R.; Berni, E.; Currie, C.J.; Treadwell, C.; Calvo, J.I.; Plastira, C.; Zafeiropoulou, E.; Odeyemi, I. Effectiveness of the capsaicin 8% patch in the management of peripheral neuropathic pain in European clinical practice: the ASCEND study. BMC Neurol., 2017, 17(1), 80.
[http://dx.doi.org/10.1186/s12883-017-0836-z] [PMID: 28431564]
[104]
Vinik, A.I.; Perrot, S.; Vinik, E.J.; Pazdera, L.; Jacobs, H.; Stoker, M.; Long, S.K.; Snijder, R.J.; van der Stoep, M.; Ortega, E.; Katz, N. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study. BMC Neurol., 2016, 16(1), 251.
[http://dx.doi.org/10.1186/s12883-016-0752-7] [PMID: 27919222]
[105]
Musharraf, M.U.; Ahmad, Z.; Yaqub, Z. Comparison of topical capsaicin and topical turpentine Oil for treatment of painful diabetic neuropathy. J. Ayub Med. Coll. Abbottabad, 2017, 29(3), 384-387.
[PMID: 29076666]
[106]
Gálvez, R.; Navez, M.L.; Moyle, G.; Maihöfner, C.; Stoker, M.; Ernault, E.; Nurmikko, T.J.; Attal, N. Capsaicin 8% patch repeat treatment in nondiabetic peripheral neuropathic pain. Clin. J. Pain, 2017, 33(10), 921-931.
[http://dx.doi.org/10.1097/AJP.0000000000000473] [PMID: 28872473]
[107]
Derry, S.; Lloyd, R.; Moore, R.A.; McQuay, H.J. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst. Rev., 2009, CD007393(4), CD007393.
[http://dx.doi.org/10.1002/14651858.CD007393.pub2] [PMID: 19821411]
[108]
Dludla, P.V.; Nkambule, B.B.; Cirilli, I.; Marcheggiani, F.; Mabhida, S.E.; Ziqubu, K.; Ntamo, Y.; Jack, B.; Nyambuya, T.M.; Hanser, S.; Mazibuko-Mbeje, S.E. Capsaicin, its clinical significance in patients with painful diabetic neuropathy. Biomed. Pharmacother., 2022, 153, 113439.
[http://dx.doi.org/10.1016/j.biopha.2022.113439] [PMID: 36076554]
[109]
Yuan, L.J.; Qin, Y.; Wang, L.; Zeng, Y.; Chang, H.; Wang, J.; Wang, B.; Wan, J.; Chen, S.H.; Zhang, Q.Y.; Zhu, J.D.; Zhou, Y.; Mi, M.T. Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns. Clin. Nutr., 2016, 35(2), 388-393.
[http://dx.doi.org/10.1016/j.clnu.2015.02.011] [PMID: 25771490]
[110]
Caterina, M.J.; Schumacher, M.A.; Tominaga, M.; Rosen, T.A.; Levine, J.D.; Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 1997, 389(6653), 816-824.
[http://dx.doi.org/10.1038/39807] [PMID: 9349813]
[111]
Caterina, M.J.; Leffler, A.; Malmberg, A.B.; Martin, W.J.; Trafton, J.; Petersen-Zeitz, K.R.; Koltzenburg, M.; Basbaum, A.I.; Julius, D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 2000, 288(5464), 306-313.
[http://dx.doi.org/10.1126/science.288.5464.306] [PMID: 10764638]
[112]
Wang, S.; Joseph, J.; Diatchenko, L.; Ro, J.Y.; Chung, M.K. Agonist-dependence of functional properties for common nonsynonymous variants of human transient receptor potential vanilloid 1. Pain, 2016, 157(7), 1515-1524.
[http://dx.doi.org/10.1097/j.pain.0000000000000556] [PMID: 26967694]
[113]
Peppin, J.F.; Pappagallo, M. Capsaicinoids in the treatment of neuropathic pain: a review. Ther. Adv. Neurol. Disord., 2014, 7(1), 22-32.
[http://dx.doi.org/10.1177/1756285613501576] [PMID: 24409200]
[114]
Yong, Y.L.; Tan, L.T.H.; Ming, L.C.; Chan, K.G.; Lee, L.H.; Goh, B.H.; Khan, T.M. The effectiveness and safety of topical capsaicin in postherpetic neuralgia: a systematic review and meta-analysis. Front. Pharmacol., 2017, 7, 538.
[http://dx.doi.org/10.3389/fphar.2016.00538] [PMID: 28119613]
[115]
Skaper, S.D.; Facci, L.; Fusco, M.; della Valle, M.F.; Zusso, M.; Costa, B.; Giusti, P. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology, 2014, 22(2), 79-94.
[http://dx.doi.org/10.1007/s10787-013-0191-7] [PMID: 24178954]
[116]
Hansen, H.S. Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Exp. Neurol., 2010, 224(1), 48-55.
[http://dx.doi.org/10.1016/j.expneurol.2010.03.022] [PMID: 20353771]
[117]
Borrelli, F.; Romano, B.; Petrosino, S.; Pagano, E.; Capasso, R.; Coppola, D.; Battista, G.; Orlando, P.; Di Marzo, V.; Izzo, A.A. Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent. Br. J. Pharmacol., 2015, 172(1), 142-158.
[http://dx.doi.org/10.1111/bph.12907] [PMID: 25205418]
[118]
Romero, T.R.L.; Duarte, I.D.G. N-palmitoyl-ethanolamine (PEA) induces peripheral antinociceptive effect by ATP-sensitive K+-channel activation. J. Pharmacol. Sci., 2012, 118(2), 156-160.
[http://dx.doi.org/10.1254/jphs.11150FP] [PMID: 22343363]
[119]
Romero, T.R.L.; Galdino, G.S.; Silva, G.C.; Resende, L.C.; Perez, A.C.; Cortes, S.F.; Duarte, I.D.G. Involvement of the L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in peripheral antinociception induced by N-palmitoyl-ethanolamine in rats. J. Neurosci. Res., 2012, 90(7), 1474-1479.
[http://dx.doi.org/10.1002/jnr.22797] [PMID: 22411529]
[120]
Costa, B.; Comelli, F.; Bettoni, I.; Colleoni, M.; Giagnoni, G. 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. Pain, 2008, 139(3), 541-550.
[http://dx.doi.org/10.1016/j.pain.2008.06.003] [PMID: 18602217]
[121]
Gatti, A.; Lazzari, M.; Gianfelice, V.; Di Paolo, A.; Sabato, E.; Sabato, A.F. Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. Pain Med., 2012, 13(9), 1121-1130.
[http://dx.doi.org/10.1111/j.1526-4637.2012.01432.x] [PMID: 22845893]
[122]
Marini, I.; Bartolucci, M.L.; Bortolotti, F.; Gatto, M.R.; Bonetti, G.A. Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain. J. Orofac. Pain, 2012, 26(2), 99-104.
[PMID: 22558609]
[123]
Schifilliti, C.; Cucinotta, L.; Fedele, V.; Ingegnosi, C.; Luca, S.; Leotta, C. Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients. Pain Res. Treat., 2014, 2014, 1-5.
[http://dx.doi.org/10.1155/2014/849623] [PMID: 24804094]
[124]
D’Amico, R.; Impellizzeri, D.; Cuzzocrea, S.; Di Paola, R. Aliamides update: Palmitoylethanolamide and its formulations on management of peripheral neuropathic pain. Int. J. Mol. Sci., 2020, 21(15), 5330.
[http://dx.doi.org/10.3390/ijms21155330] [PMID: 32727084]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy