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Hama AT, Pearson JP, Sagen J. Effects of repeated dosing with mechanistically distinct antinociceptive ligands in a rat model of neuropathic spinal cord injury pain. Pharmacol Res Perspect. 2014;2(2):e00034doi: 10.1002/prp2.34.
Hama, A. T., Pearson, J. P., & Sagen, J. (2014). Effects of repeated dosing with mechanistically distinct antinociceptive ligands in a rat model of neuropathic spinal cord injury pain. Pharmacology research & perspectives, 2(2), e00034. https://doi.org/10.1002/prp2.34
Hama, Aldric T, et al. "Effects of repeated dosing with mechanistically distinct antinociceptive ligands in a rat model of neuropathic spinal cord injury pain." Pharmacology research & perspectives vol. 2,2 (2014): e00034. doi: https://doi.org/10.1002/prp2.34
Hama AT, Pearson JP, Sagen J. Effects of repeated dosing with mechanistically distinct antinociceptive ligands in a rat model of neuropathic spinal cord injury pain. Pharmacol Res Perspect. 2014 Apr;2(2):e00034. doi: 10.1002/prp2.34. Epub 2014 Mar 13. PMID: 25505583; PMCID: PMC4184706.
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Pharmacol Res Perspect. 2014 Apr;2(2):e00034. doi: 10.1002/prp2.34. Epub 2014 Mar 13.

Effects of repeated dosing with mechanistically distinct antinociceptive ligands in a rat model of neuropathic spinal cord injury pain.

Pharmacology research & perspectives

Aldric T Hama, James P Pearson, Jacqueline Sagen

Affiliations

  1. The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine Miami, Florida, 33136.
  2. Ironwood Pharmaceuticals, Inc. Cambridge, Massachusetts, 02142.

PMID: 25505583 PMCID: PMC4184706 DOI: 10.1002/prp2.34

Abstract

A lack of efficacy of some analgesic drugs has been previously described in rats with neuropathic spinal cord injury (SCI) pain. It has been suggested that repeated dosing in these animals over time may eventually lead to efficacy. However, it is also possible that efficacy may diminish over time with repeated dosing. This study evaluated the efficacy of various drugs upon repeated dosing over time in a rat model of SCI pain. Four weeks following an acute spinal cord compression at the mid-thoracic level, rats developed decreased hind paw withdrawal threshold, suggestive of below level neuropathic hypersensitivity. Either cannabinoid (CB) receptor agonist CP 55,940, the anticonvulsant carbamazepine or gabapentin, the antidepressant amitriptyline or vehicle was administered over a period of 7 days. Neither carbamazepine nor amitriptyline demonstrated efficacy either after a single or repeated dosing. Beginning with a 50% efficacious dose of gabapentin, the effect of gabapentin in SCI rats neither increased nor decreased over the treatment period. The antinociceptive effect of CP 55,940 was maintained for the entire treatment period, which was mediated by CB1 but not CB2 receptors. The current data suggest that sustained antinociception can be obtained with some drugs in rats with neuropathic SCI pain. Furthermore, the current data do not substantiate the notion that repeated treatment with initially ineffective drugs will eventually lead to efficacy; treatments that are not acutely effective are unlikely to demonstrate clinical efficacy.

Keywords: Acute drug challenge; amitriptyline; below level neuropathic pain; cannabinoid receptor agonist; carbamazepine; repeated drug dosing

References

  1. J Pharmacol Exp Ther. 2004 Nov;311(2):576-84 - PubMed
  2. Prog Neurobiol. 1999 Jan;57(1):1-164 - PubMed
  3. Pain. 2001 Feb 15;90(3):217-26 - PubMed
  4. J Neurosci Methods. 1994 Jul;53(1):55-63 - PubMed
  5. Behav Pharmacol. 2004 Feb;15(1):1-12 - PubMed
  6. Neurology. 2005 Aug 9;65(3):444-7 - PubMed
  7. Brain Res. 1997 May 9;756(1-2):141-6 - PubMed
  8. Life Sci. 1996;58(15):1239-47 - PubMed
  9. J Rehabil Res Dev. 2009;46(1):135-43 - PubMed
  10. J Pharmacol Exp Ther. 2004 Aug;310(2):620-32 - PubMed
  11. Eur J Pharmacol. 2004 May 3;491(2-3):137-48 - PubMed
  12. Pain. 2004 Dec;112(3):372-80 - PubMed
  13. Pediatrics. 2010 May;125(5):e1208-25 - PubMed
  14. Health Technol Assess. 1997;1(6):i-iv, 1-135 - PubMed
  15. J Spinal Cord Med. 2006;29(2):109-17 - PubMed
  16. Chem Biodivers. 2007 Aug;4(8):1729-43 - PubMed
  17. J Pharmacol Exp Ther. 2002 Dec;303(3):1199-205 - PubMed
  18. Pain. 2011 Mar;152(3):649-55 - PubMed
  19. J Rehabil Res Dev. 2005 Sep-Oct;42(5):573-84 - PubMed
  20. Pain. 2001 May;92 (1-2):91-100 - PubMed
  21. Biochem Pharmacol. 2008 Jan 1;75(1):85-97 - PubMed
  22. Ann N Y Acad Sci. 1976;282:221-39 - PubMed
  23. Exp Neurol. 2007 Mar;204(1):454-7 - PubMed
  24. J Rehabil Res Dev. 2009;46(1):95-107 - PubMed
  25. Pain. 2004 May;109 (1-2):124-31 - PubMed
  26. J Rehabil Res Dev. 2009;46(1):1-12 - PubMed
  27. Pain. 1999 Mar;80(1-2):391-8 - PubMed
  28. Brain Res. 2007 Dec 14;1185:117-28 - PubMed
  29. Jpn J Pharmacol. 1999 Jan;79(1):65-73 - PubMed
  30. Pain. 1987 Nov;31(2):225-36 - PubMed
  31. J Neurosurg. 1968 Jul;29(1):48-50 - PubMed
  32. Neuropharmacology. 2005 Feb;48(2):252-63 - PubMed
  33. Neurosci Lett. 2000 Feb 25;280(3):211-4 - PubMed
  34. Mol Pharmacol. 1997 Jun;51(6):1077-83 - PubMed
  35. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7731-6 - PubMed
  36. Pain. 1999 Feb;79(2-3):281-90 - PubMed
  37. J Neurosci. 2001 Mar 15;21(6):1868-75 - PubMed
  38. Neuropharmacology. 2009 Sep;57(3):235-41 - PubMed
  39. Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):7-12 - PubMed
  40. Br J Pharmacol. 2004 Jan;141(1):4-8 - PubMed

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