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Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats.
Eur J Pharmacol. 2008 Jun 10; 587(1-3):104-11.EJ

Abstract

The present study was designed to investigate the ameliorative effects of clinically available drugs, with Na+/Ca2+ and Na+/H+ exchange inhibitory actions, in chronic constriction injury and vincristine induced painful neuropathy in rats. Sciatic nerve ligation and vincristine treatment (50 microg/kg for 10 days) was employed to induce neuropathy in rats. Paw pressure, von Frey hair, acetone drop, and tail heat immersion tests were performed to assess degree of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal thermal sensation respectively. Axonal degeneration of sciatic nerve was assessed histopathologically. The levels of thio-barbituric acid reactive species, reduced glutathione, and total calcium were determined to assess biochemical alterations. Amiloride (15 mg/kg i.p.), Na+/Ca2+ and Na+/H+ exchange inhibitor, and pralidoxime (20 mg/kg i.p.), Na+/Ca2+ exchange inhibitor, were administered for 10 consecutive days starting from the day of surgery or vincristine administration. Sciatic nerve ligation and vincristine treatment resulted in significant axonal degeneration, development of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal heat hyperalgesia and also resulted in rise in thio-barbituric acid reactive species, total calcium and decrease in reduced glutathione levels. Administration of amiloride and pralidoxime attenuated chronic constriction injury and vincristine induced axonal degeneration and reduction of nociceptive threshold along with reduction in calcium levels and oxidative stress. The observed anti-nociceptive effects of amiloride and pralidoxime may possibly be attributed to inhibition of Na+/Ca2+ and Na+/H+ exchangers with subsequent decrease in Ca2+ ions and oxidative stress.

Authors+Show Affiliations

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147002, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18486127

Citation

Muthuraman, Arunachalam, et al. "Ameliorative Effects of Amiloride and Pralidoxime in Chronic Constriction Injury and Vincristine Induced Painful Neuropathy in Rats." European Journal of Pharmacology, vol. 587, no. 1-3, 2008, pp. 104-11.
Muthuraman A, Jaggi AS, Singh N, et al. Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats. Eur J Pharmacol. 2008;587(1-3):104-11.
Muthuraman, A., Jaggi, A. S., Singh, N., & Singh, D. (2008). Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats. European Journal of Pharmacology, 587(1-3), 104-11. https://doi.org/10.1016/j.ejphar.2008.03.042
Muthuraman A, et al. Ameliorative Effects of Amiloride and Pralidoxime in Chronic Constriction Injury and Vincristine Induced Painful Neuropathy in Rats. Eur J Pharmacol. 2008 Jun 10;587(1-3):104-11. PubMed PMID: 18486127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats. AU - Muthuraman,Arunachalam, AU - Jaggi,Amteshwar Singh, AU - Singh,Nirmal, AU - Singh,Dhandeep, Y1 - 2008/04/08/ PY - 2007/11/14/received PY - 2008/03/03/revised PY - 2008/03/13/accepted PY - 2008/5/20/pubmed PY - 2008/8/30/medline PY - 2008/5/20/entrez SP - 104 EP - 11 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 587 IS - 1-3 N2 - The present study was designed to investigate the ameliorative effects of clinically available drugs, with Na+/Ca2+ and Na+/H+ exchange inhibitory actions, in chronic constriction injury and vincristine induced painful neuropathy in rats. Sciatic nerve ligation and vincristine treatment (50 microg/kg for 10 days) was employed to induce neuropathy in rats. Paw pressure, von Frey hair, acetone drop, and tail heat immersion tests were performed to assess degree of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal thermal sensation respectively. Axonal degeneration of sciatic nerve was assessed histopathologically. The levels of thio-barbituric acid reactive species, reduced glutathione, and total calcium were determined to assess biochemical alterations. Amiloride (15 mg/kg i.p.), Na+/Ca2+ and Na+/H+ exchange inhibitor, and pralidoxime (20 mg/kg i.p.), Na+/Ca2+ exchange inhibitor, were administered for 10 consecutive days starting from the day of surgery or vincristine administration. Sciatic nerve ligation and vincristine treatment resulted in significant axonal degeneration, development of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal heat hyperalgesia and also resulted in rise in thio-barbituric acid reactive species, total calcium and decrease in reduced glutathione levels. Administration of amiloride and pralidoxime attenuated chronic constriction injury and vincristine induced axonal degeneration and reduction of nociceptive threshold along with reduction in calcium levels and oxidative stress. The observed anti-nociceptive effects of amiloride and pralidoxime may possibly be attributed to inhibition of Na+/Ca2+ and Na+/H+ exchangers with subsequent decrease in Ca2+ ions and oxidative stress. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18486127/Ameliorative_effects_of_amiloride_and_pralidoxime_in_chronic_constriction_injury_and_vincristine_induced_painful_neuropathy_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00355-5 DB - PRIME DP - Unbound Medicine ER -