Generic placeholder image

Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Alcoholic Neuropathy: Involvement of Multifaceted Signalling Mechanisms

Author(s): Tapan Behl*, Harlokesh N. Yadav and Pyare L. Sharma

Volume 14, Issue 1, 2021

Published on: 12 May, 2020

Page: [2 - 10] Pages: 9

DOI: 10.2174/1874467213666200512114943

Price: $65


Background: Alcoholic neuropathy is a chronic disorder caused by the excessive consumption of alcohol. Damage to the nerves results in unusual sensations in the limbs, decreased mobility and loss of some body functions.

Objective: Alcohol is considered a major cause for exclusively creating the debilitating condition of the neuropathic state. This review critically examines the key mediators involved in the pathogenesis of alcoholic neuropathy and the targets, which, upon selective inhibition, alleviate the progression of alcoholic neuropathy.

Methods: A thorough study of research and review articles available on the internet from PubMed, MEDLINE, and concerned sites was performed on alcoholic neuropathy.

Result: Impairment in axonal transportation is quite common with the progression of alcoholic neuropathy. Nutritional deficiencies lead to axonal neuropathies that escalate a variety of complications that further worsen the state. PKC and PKA play a significant role in the pathogenesis of alcoholic neuropathy. PKC plays a marked role in modulating NMDA receptor currents, manifesting excitations in neurons. MMPs are involved in the number of pathologies that destroy the CNS and reduction in the level of endogenous antioxidants like α-tocopherol, vitamin E with ethanol, promotes oxidative stress by generating free radicals and lipid peroxidation.

Conclusion: Oxidative stress is implicated in the activation of MMPs, causing disruption in the blood-brain barrier, the latter are involved in the trafficking and passage of molecules in and out of the cell. Chronic alcohol consumption leads to the downregulation of CNS receptors, consequently precipitating the condition of alcoholic neuropathy.

Keywords: Alcohol, neuropathy, protein kinase, dopamine, endocannabinoids, cytokines.

Graphical Abstract
Tracey, K.J. Neuron are the inflammatory problems. Cell, 2018, 173(5), 1066-1068.
[] [PMID: 29775588]
Miyoshi, G.; Hjerling-Leffler, J.; Karayannis, T.; Sousa, V.H.; Butt, S.J.; Battiste, J.; Johnson, J.E.; Machold, R.P.; Fishell, G. Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J. Neurosci., 2010, 30(5), 1582-1594.
[] [PMID: 20130169]
Walter, L.J.; McAllister, T.A.; Yang, W.Z.; Beauchemin, K.A.; He, M.; McKinnon, J.J. Comparison of wheat or corn dried distillers grains with solubles on rumen fermentation and nutrient digestibility by feedlot heifers. J. Anim. Sci., 2012, 90(4), 1291-1300.
[] [PMID: 22021811]
Pullen, Richard L.; Ruiz, Gerardo A. Management of alcohol-induced peripheral neuropathy. Nurs. Made Incred. Easy, 2019, 17(6), 28-36.
Koike, T.; Tanabe, H. C; Okazaki, S.; Nakagawa Sasaki AT.; Shimada K.; Sugawara SK.; Takahashi HK.; Yoshihara K.; Bosch-Bayard J.; Sadato N. Neural substrate of shared attention as social memory: A hyper scanning functional magnetic resonance imaging study. Neuroimage, 2016, 125, 401-412.
[] [PMID: 26514295]
Lee, A.; Lim, W.; Kim, S.; Khil, H.; Cheon, E.; An, S.; Hong, S.; Lee, D.H.; Kang, S.S.; Oh, H.; Keum, N.; Hsieh, C.C. Coffee Intake and Obesity: A Meta-Analysis. Nutrients, 2019, 11(6), E1274.
[] [PMID: 31195610]
Padi, S.S.; Kulkarni, S.K. Minocycline prevents the development of neuropathic pain, but not acute pain: possible anti-inflammatory and antioxidant mechanisms. Eur. J. Pharmacol., 2008, 601(1-3), 79-87.
[] [PMID: 18952075]
Julian, T.; Glascow, N.; Syeed, R.; Zis, P. Alcohol-related peripheral neuropathy: A systematic review and meta-analysis. J. Neurol., 2019, 266(12), 2907-2919.
[] [PMID: 30467601]
Scott, E.; Leandro, F.V.; Nicholas, W.G.; Marcin, W.; Katie, W. Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies. Alcohol. Clin. Exp. Res., 2019.
Yerdelen, D.; Koc, F.; Uysal, H. Strength-duration properties of sensory and motor axons in alcoholic polyneuropathy. Neurol. Res., 2008, 30(7), 746-750.
[] [PMID: 18489821]
Rintala, D.H.; Holmes, S.A.; Courtade, D.; Fiess, R.N.; Tastard, L.V.; Loubser, P.G. Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury. Arch. Phys. Med. Rehabil., 2007, 88(12), 1547-1560.
[] [PMID: 18047869]
Sandercock, P.A.; Counsell, C.; Kane, E.J. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst. Rev., 2015, 12(3), CD000024.
[] [PMID: 25764172]
Perez, M.J.; Kong, L.; Sumner, G.; Tizano, E. Developmental aspects and pathological fidinf in spinal muscular atrophy. Dis. Mech. Ther.,, 2017, 22, 21-42.
Scott, R.; Robert, H. Alcoholic neuropathy. Drug and disease, 2019.
Rauck, R.L.; Hong, K.J.; North, J. Opioid induced constipation survey in patients with chronic noncancer pain. Pain Pract., 2017, 17(3), 329-335.
[] [PMID: 26990277]
Ziegler, D.; Rewers, A.; Olli, Simell.; Johanna L.; Andrea S.; Christiane W.; Jorma I.; Riitta V.; Mikael K.; Ezio B.; George S. Seroconversion to multiple islet autoantibodies and risk of progression to children in diabetes. JAMA, 2013, 309(23), 2473-2479.
[] [PMID: 23780460]
Mellion, M.L.; Meliton, A; Moldobaeva, N.; Mutlu, G.; Kawasaki Y.; Akiyama T.; Birukova, AA. Asef mediates HGF protective effect against LPS induced lung injury and endothelial dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol., 2015, 308(50), 452-463.
Zambelis, T.; Oulis, P.; Zambelis, T.; Kokotis, P.; Koulouris, G.; Karandreas, G. Clinical and neurophysiology study of peroneal nerve mononeuropathy after substantial weight loss in patients suffering from major depressive and schizophrenic disorder: suggestion on patient’s management. J .Periph. Nerv .Sys., 2008, 3 Article 24
Zachary, M.; Kate, K.; Gair, R.; Corrigan, T.; Corrigan, J. Juvenile traumatic brain injury increase alcohol consumption and reward in female mice. J. Neurotruma, 2008, 33(9), 895-903.
Jessica, R.; Sara, D. Medicinal marijuana for peripheral neuropathy. The foundation of peripheral neuropathy, 2019. Available at: for-peripheral-neuropathy/ (Accessed on November 1, 2019).
Miyoshi, K.; Jens, H.; Theofanis, K.; Vitor, H.; Sousa.; Simon J. B. Butt.; James B.; Jane E. Johnson.; Robert P.; and Gord, F. Genetic fate mapping reveals that the caudal ganglionic eminence produces and diverse population of superficial cortical internurons. J. Neurosci., 2010, 30(5), 1582-1594.
[] [PMID: 20130169]
Rudroff, T. Cannabis for Neuropathic Pain in Multiple Sclerosis-High Expectations, Poor Data. Front. Pharmacol., 2019, 10, 1239.
[] [PMID: 31695613]
Thayer, J.F.; Ahs, F.; Fredrikson, M.; Sollers, J.J.; Wager, T.D. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci. Biobehav. Rev., 2012, 36(2), 747-756.
[] [PMID: 22178086]
Debra, A.K.; Guillermo, A.Y. Cannabinoid receptor in central nervous system: Their role and signaling in disease. Front Cell Neurosci, 2016, 10
Stefanie, U.; Vandael, D.; Marcantoni, A.; Dedic, N.; Bilbao, A.; Vogt, M.A.; Hirth, N.; Broccoli, L.; Bernardi, R.E.; Schönig, K.; Gass, P.; Bartsch, D.; Spanagel, R.; Deussing, J.M.; Sommer, W.H.; Carbone, E.; Hansson, A.C. Differential roles of L- type calcium channel subtypes in alcohol dependence. Neuropsycopharamcology, 2017, 42(5), 1058-1069.
Bie, B.; Wu, J.; Foss, J.F.; Naguib, M. An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Curr. Opin. Anaesthesiol., 2018, 31(4), 407-414.
[] [PMID: 29794855]
Masocha, W. Targeting the Endocannabinoid System for Prevention or Treatment of Chemotherapy-Induced Neuropathic Pain: Studies in Animal Models. Pain. Res. Manag., 2018.
Chye, Y.; Christensen, E.; Solowij, N.; Yücel, M. The endocannabinoid system and cannabidiol promise for the treatment of substance use disorder. Front. Psychiatry, 2019, 10, 63.
[] [PMID: 30837904]
Kaur, R.; Ambwani, S.R.; Singh, S. Endocannabinoid system: a multi-facet therapeutic target. Current clinical pharmacology, 2016, 11(2), 110-117.
Dhopeshwarkar, A.; Mackie, K. CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Mol. Pharmacol., 2014, 86(4), 430-437.
[] [PMID: 25106425]
Zou, S.; Kumar, U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int. J. Mol. Sci., 2018, 19(3), 833.
[] [PMID: 29533978]
Lu, H.C.; Mackie, K. An Introduction to the Endogenous Cannabinoid System. Biol. Psychiatry, 2016, 79(7), 516-525.
[] [PMID: 26698193]
Cippitelli, A.; Schoch, J.; Debevec, G.; Brunori, G.; Zaveri, N.T.; Toll, L. A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration. Sci. Rep., 2016, 6, 26594.
[] [PMID: 27199205]
Console, L.; Maruc, L.; Abood, M.E. Cannabinoid receptors: nomenclature and pharmacological principles. Prog neurpsychopharmacol biol psychiatry., 2012, 38910, 4-15.
Shuba, G.; Warner, B.; Dennis, R.; Craig, J.; Irina, A. Rodent Model of alcohol liver disease: Role of Binge ethanol administration. Biomolecules, 2018, 8(3), 1-21.
Patrcyja , k.; Smaga , I.; Filip, M.; Zadrozyny , M. Cannaboinoids ligands and Alcohol addiction: A promising therapeutic tool. Neuro.toxicity, 2016, 29(1), 173-196.
García, C.; Palomo-Garo, C.; Gómez-Gálvez, Y.; Fernández-Ruiz, J. Cannabinoid-dopamine interactions in the physiology and physiopathology of the basal ganglia. Br. J. Pharmacol., 2016, 173(13), 2069-2079.
[] [PMID: 26059564]
Liu, Q.R.; Canseco-Alba, A.; Zhang, H.Y.; Tagliaferro, P.; Chung, M.; Dennis, E.; Sanabria, B.; Schanz, N.; Escosteguy-Neto, J.C.; Ishiguro, H.; Lin, Z.; Sgro, S.; Leonard, C.M.; Santos-Junior, J.G.; Gardner, E.L.; Egan, J.M.; Lee, J.W.; Xi, Z.X.; Onaivi, E.S. Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference. Sci. Rep., 2017, 7(1), 17410.
[] [PMID: 29234141]
Sisi, l.; Zeng, J.; Wan, X.; Yao, Y.; Zhao, N. Yu, Y.; Yu, C.; Xia, C. Enhancement of spinal dorsal horn neuron NMDA receptor phosphorylation as the mechanism of remifentanil induced hyperalgesia. Mol. Pain, 2012, 13. Available at: (Accessed on November 1, 2020).
Callender, J.A.; Newton, A.C. Conventional protein kinase C in the brain: 40 years later. Neuronal Signaling, 2012, 1(2), Article NS20160005.
Vanderwall, A.G.; Milligan, E.D. Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management. Front. Immunol., 2019, 10, 3009.
[] [PMID: 31921220]
Jardín, I.; López, J.J.; Diez, R.; Sánchez-Collado, J.; Cantonero, C.; Albarrán, L.; Woodard, G.E.; Redondo, P.C.; Salido, G.M.; Smani, T.; Rosado, J.A. TRPs in Pain sensation. Front. Physiol., 2017, 8, 392.
[] [PMID: 28649203]
Bu, F.; Tian, H.; Gong, S.; Zhu, Q.; Xu, G.Y.; Tao, J.; Jiang, X. Phosphorylation of NR2B NMDA subunits by protein kinase C in arcuate nucleus contributes to inflammatory pain in rats. Sci. Rep., 2015, 5, 15945.
[] [PMID: 26515544]
Cailong, P.; Wang, C.; Zhang, L.; Song, L.; Chen, Y.; Liu, B.; Liu, T.; Hu, L.; Pan, Y. Procyanidins attenuate neuropathic pain suppressing matrix metalloproteinase-9/2; Neuroinflammation, 2018, p. 187.
Kawasaki, A.; Purvin, V.A.; Burgett, R.A. Hyperhomocysteinaemia in young patients with non-arteritic anterior ischaemic optic neuropathy. Br. J. Ophthalmol., 1999, 83(11), 1287-1290.
[] [PMID: 10535859]
Remacle, A.G.; Hullugundi, S.K.; Dolkas, J.; Angert, M.; Chernov, A.V.; Strongin, A.Y.; Shubayev, V.I. Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury. J. Neuroinflammation, 2018, 15(1), 89.
[] [PMID: 29558999]
Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Münch, A.E.; Chung, W.S.; Peterson, T.C.; Wilton, D.K.; Frouin, A.; Napier, B.A.; Panicker, N.; Kumar, M.; Buckwalter, M.S.; Rowitch, D.H.; Dawson, V.L.; Dawson, T.M.; Stevens, B.; Barres, B.A. Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 2017, 541(7638), 481-487.
[] [PMID: 28099414]
Priscilla, M.; Lars, L.; Sarah, Z.; Jørgen, G.B J. Neuroimmunol., 2018, 318, 80-86.
[] [PMID: 29500107]
Yu, L.; Sun, L.W.; Yah, M. Research Progress of the role and mechanism of extracellular signal regulated protein kinase 5 (ERK5) in pathological pain. J. Neurochem., 2016, 17(10), 733-744.
[] [PMID: 27704743]
Chopra, K.; Tiwari, V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br. J. Clin. Pharmacol., 2012, 73(3), 348-362.
[] [PMID: 21988193]
Dina, O.A.; Khasar, S.G.; Alessandri-Haber, N.; Green, P.G.; Messing, R.O.; Levine, J.D. Alcohol-induced stress in painful alcoholic neuropathy. Eur. J. Neurosci., 2008, 27(1), 83-92.
[] [PMID: 18093169]
Henderson-Redmond, A.N.; Guindon, J.; Morgan, D.J. Roles for the endocannabinoid system in ethanol-motivated behavior. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2016, 65, 330-339.
[] [PMID: 26123153]
Pava, M.J.; Woodward, J.J. A review of the interactions between alcohol and the endocannabinoid system: implications for alcohol dependence and future directions for research. Alcohol, 2012, 46(3), 185-204.
[] [PMID: 22459871]
Adam, S.; Richard, C.H. Alcoholic neuropathy; Star Pearls, 2019.

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