Analgesic effect of cardiotonic steroids in rats with alcoholic neuropathy

Authors

  • Vladimir A. Kashkin Pavlov First Saint Petersburg State Medical University; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences https://orcid.org/0000-0002-7202-0233

DOI:

https://doi.org/10.33910/2687-1270-2020-1-2-133-139

Keywords:

marinobufagenin, alcoholic neuropathy, ouabain, Na/K-ATPase, rats

Abstract

The present study aimed to assess the possible antinociceptive effect of cardiotonic steroids during the development of alcoholic neuropathy. The pathology was formed in rodents by means of forced alcohol consumption in increasing concentration. The force consumption of high doses of alcohol for 8 weeks allowed us to model a symptomatic complex typical for alcoholic neuropathy. During consequent modelling of the acute alcohol withdrawal syndrome, it was established that on the second day after the withdrawal there was an increase in the renal excretion of marinobufagenin, an alpha-1 isoform inhibitor of Na/K-ATPase, with a simultaneous increase in the threshold of tactile allodynia; that indicated the involvement of cardiotonic steroids in the process of nociception in alcohol dependence. The concentration of marinobufagenin in urine was measured by enzyme-linked immunoassay. It was also demonstrated that intraperitoneally administered ouabain, an alpha-3 isoform inhibitor of Na/K-ATPase, significantly increased the threshold of tactile allodynia, indicating a pronounced analgesic effect of the steroid. These data suggest that the system of Na/K-ATPase and its endogenous ligands has therapeutic potential against the development of chronic pain associated with alcohol dependence.

References

Bagrov, Y. Y., Dmitrieva, N. I., Manusova, N. B. et al. (1999) Involvement of endogenous digitalis-like factors in voluntary selection of alcohol by rats. Life Sciences, vol. 64, no. 20, pp. PL219–PL225. DOI: 10.1016/s0024-3205(99)00131-9 (In English)

Belozertseva, I. V. (comp.). (2014) Rukovodstvo po ispol’zovaniyu laboratornykh zhivotnykh dlya nauchnykh i uchebnykh tselei v PSPbGMU im. I. P. Pavlova [Handbook on use of laboratory animals for scientific and educational purposes in First Pavlov State Medical University of Saint Petersburg]. 2nd ed. Saint Petersburg: First Pavlov State Medical University of Saint Petersburg Publ., 79 p. (In Russian)

Bosch-Morell, F., Martínez-Soriano, F., Colell, A. et al. (1998) Chronic ethanol feeding induces cellular antioxidants decrease and oxidative stress in rat peripheral nerves. Effect of S-adenosyl-L-methionine and N-acetyl-L-cysteine. Free Radical Biology & Medicine, vol. 25, no. 3, pp. 365–368. PMID: 9680183. DOI: 10.1016/s0891-5849(98)00036- 7 (In English)

Chaplan, S. R., Bach, F. W., Pogrel, J. W. et al. (1994) Quantitative assessment of tactile allodynia in the rat paw. Journal of Neuroscience Methods, vol. 53, no. 1, pp. 55–63. PMID: 7990513. DOI: 10.1016/0165-0270(94)90144- 9 (In English)

Chopra, K., Tiwari, V. (2012) Alcoholic neuropathy: Possible mechanisms and future treatment possibilities. British Journal of Clinical Pharmacology, vol. 73, no. 3, pp. 348–362. PMID: 21988193. DOI: 10.1111/j.1365-2125.2011.04111.x (In English)

Claus, D., Eggers, R., Engelhardt, A. et al. (1985) Ethanol and polyneuropathy. Acta Neurologica Scandinavica, vol. 72, no. 3, pp. 312–316. DOI: 10.1111/j.1600-0404.1985.tb00876.x (In English)

Cohen, A. C., Tong, M., Wands, J. R., de la Monte, S. M. (2007) Insulin and insulin-like growth factor resistance with neurodegeneration in an adult chronic ethanol exposure model. Alcoholism: Clinical and Experimental Research, vol. 31, no. 9, pp. 1558–1573. PMID: 17645580. DOI: 10.1111/j.1530-0277.2007.00450.x (In English)

de la Monte, S. M., Longato, L., Tong, M. et al. (2009) The liver-brain axis of alcohol-mediated neurodegeneration: Role of toxic lipids. International Journal of Environmental Research and Public Health, vol. 6, no. 7, pp. 2055–2075. PMID: 19742171. DOI: 10.3390/ijerph6072055 (In English)

de la Monte, S. M., Xu, X. J., Wands, J. R. (2005) Ethanol inhibits insulin expression and actions in the developing brain. Cellular and Molecular Life Sciences, vol. 62, no. 10, pp. 1131–1145. PMID: 15870954. DOI: 10.1007/s00018-005-4571-z (In English)

de la Monte, S. M., Yeon, J. E., Tong, M. et al. (2008) Insulin resistance in experimental alcohol-induced liver disease. Journal of Gastroenterology and Hepatology, vol. 23, no. 8, pt 2, pp. e477–e486. PMID: 18505416. DOI: 10.1111/j.1440-1746.2008.05339.x (In English)

Dixon, W. J. (1980) Efficient analysis of experimental observations. Annual Review of Pharmacology and Toxicology, vol. 20, pp. 441–462. PMID: 7387124. DOI: 10.1146/annurev.pa.20.040180.002301 (In English)

Fedorova, O. V., Talan, M. I., Agalakova, N. I. et al. (2002) Endogenous ligand of α1 sodium pump, marinobufagenin, is a novel mediator of sodium chloride-dependent hypertension. Circulation, vol. 105, no. 9, pp. 1122–1127. PMID: 11877366. DOI: 10.1161/hc0902.104710 (In English)

Kashkin, V. A., Bagrov, A. Y., Fedorova, O. V. et al. (2002) Marinobufagenin (MBG) suppression of ethanol-seeking behavior is associated with inhibition of brain cortex Na/K-ATPase in mice. European Neuropsychopharmacoly, vol. 12, no. 3, pp. 217–223. DOI: 10.1016/S0924-977X(02)00026-3 (In English)

Kashkin, V. A., Shekunova, E. V., Muzhikyan, A. A. et al. (2016) Model’ alkogol’noj nejropatii u krys [Experimental models of alcoholic neuropathy in rats]. Ehksperimental’naya i klinicheskaya farmakologiya — Experimental and Clinical Pharmacology, vol. 79, no. 12, pp. 29–33. (In Russian).

Kashkin, V. A., Zvartau, E. E., Fedorova, O. V. et al (2008) Endogenous bufadienolide mediates pressor response to ethanol withdrawal in rats. European Neuropsychopharmacoly, vol. 18, no. 1, pp. 74–77. PMID: 17683916. DOI: 10.1016/j.euroneuro.2007.05.006 (In English)

Koike, H., Iijima, M., Sugiura, M. et al. (2003) Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Annals of Neurology, vol. 54, no. 1, pp. 19–29. PMID: 12838517. DOI: 10.1002/ana.10550 (In English)

Krylov, B. V., Derbenev, A. V., Podzorova, S. A. et al. (2000). Morphine decreases the voltage sensitivity of slow sodium channels. Neuroscience and Behavioral Physiology, vol. 30, pp. 431–439. DOI: 10.1007/bf02463098 (In English)

Lopatina, E. V., Yachnev, I. L., Penniyaynen, V. A. et al. (2012) Modulation of signal-transducing function of neuronal membrane Na+,K+-ATPase by endogenous ouabain and low-power infrared radiation leads to pain relief. Medicinal Chemistry, vol. 8, no. 1, pp. 33–39. PMID: 22420548. DOI: 10.2174/157340612799278531 (In English)

Mellion, M. L., Nguyen, V., Tong, M. et al. (2013) Experimental model of alcohol-related peripheral neuropathy. Muscle & Nerve, vol. 48, no. 2, pp. 204–211. PMID: 23761140. DOI: 10.1002/mus.23744 (In English)

Monforte, R., Estruch, R., Valls-Solé, J. et al. (1995) Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose-related toxic effect of alcohol. Archives of Neurology, vol. 52, no. 1, pp. 45–51. PMID: 7826275. DOI: 10.1001/archneur.1995.00540250049012 (In English)

O’Brien, W. J., Lingrel, J. B., Wallick, E. T. (1994) Ouabain binding kinetics of the rat alpha two and alpha three isoforms of the sodium-potassium adenosine triphosphate. Archives of Biochemistry and Biophysics, vol. 310, no. 1, pp. 32–39. PMID: 8161218. DOI: 10.1006/abbi.1994.1136 (In English)

Ou-Yang, H. D., Zeng, W. A., Li, Q. et al. (2008) Effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats. Nan fang yi ke da xue xue bao — Journal of Southern Medical University, vol. 28, no. 10, pp. 1760–1763. PMID: 18971165. (In Chinese)

Persson, A. K., Kim, I., Zhao, P. et al. (2013a) Sodium channels contribute to degeneration of dorsal root ganglion neurites induced by mitochondrial dysfunction in an in vitro model of axonal injury. The Journal of Neuroscience, vol. 33, no. 49, pp. 19250–19261. PMID: 24305821. DOI: 10.1523/JNEUROSCI.2148-13.2013 (In English)

Persson, A. K., Liu, S., Faber, C. G. et al. (2013b) Neuropathy-associated Nav1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons. Annals of Neurology, vol. 73, no. 1, pp. 140–145. PMID: 23280954. DOI: 10.1002/ana.23725 (In English)

Zeng, W., Chen, X., Dohi, S. (2007) Antinociceptive synergistic interaction between clonidine and ouabain on thermal nociceptive tests in the rat. The Journal of Pain: Official Journal of the American Pain Society, vol. 8, no. 12, pp. 983–988. PMID: 17892975. DOI: 10.1016/j.jpain.2007.07.006 (In English)

Zeng, W., Dohi, S., Shimonaka, H., Asano, T. (1999) Spinal antinociceptive action of Na+–K+ pump inhibitor ouabain and its interaction with morphine and lidocaine in rats. Anesthesiology, vol. 90, no. 2, pp. 500–508. PMID: 9952158. DOI: 10.1097/00000542-199902000-00026 (In English)

Published

2020-06-05

Issue

Section

Experimental articles