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Open Pain J. 2013;6:95-107. doi: 10.2174/1876386301306010095. Epub 2013 Mar 08.

Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine.

The open pain journal

Michael J Iadarola, Gian Luigi Gonnella

Affiliations

  1. Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, NIH; Building 49 Room 1C20, 49 Convent Drive MSC 4410, Bethesda MD 20892-4410, USA.
  2. Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, NIH; Department of Anesthesiology and Intensive Care Medicine, Catholic University School of Medicine, Rome, Italy.

PMID: 26779292 PMCID: PMC4711370 DOI: 10.2174/1876386301306010095

Abstract

This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. Like capsaicin, RTX is a vanilloid receptor (TRPV1) agonist, only more potent. This increased potency confers both quantitative and qualitative advantages in terms of drug action on the TRPV1 containing nerve terminal, which result in an increased efficacy and a long duration of action. RTX can be delivered by a central route of administration through injection into the subarachnoid space around the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where primary afferents nerves terminate, or directly into a nerve trunk or a dorsal root ganglion. The central route is currently being evaluated as a treatment for intractable pain in patients with advanced cancer. Peripheral administration offers the possibility to treat a wide diversity of pain problems because of the ability to bring the treatment to the site of the pain (the peripheral generator). While not all pain disorders are appropriate for RTX, tailoring treatment to an individual patient's needs via a selective and local intervention that chemically targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine.

Keywords: A-delta fibers; C-fibers; CGRP; Calcium cytotoxicity; Substance P; arachnoiditis; cancer pain; complex regional pain syndrome; dog; endoplasmic reticulum; geriatric; ion channel; malignant pain; mitochondria; neuropathic pain; non-malignant pain; osteoarthritis; osteosarcoma; plasma membrane; spinal stenosis

References

  1. J Neurochem. 2007 Nov;103(4):1628-43 - PubMed
  2. Anesth Analg. 2008 Jul;107(1):282-91 - PubMed
  3. Anesthesiology. 2005 Nov;103(5):1052-9 - PubMed
  4. Ann Anat. 2011 Jul;193(4):267-75 - PubMed
  5. J Pharmacol Exp Ther. 2012 Jan;340(1):152-60 - PubMed
  6. Bioorg Med Chem. 2008 Oct 15;16(20):9349-58 - PubMed
  7. J Clin Invest. 2004 May;113(9):1344-52 - PubMed
  8. Nat Rev Drug Discov. 2011 Aug 01;10(8):601-20 - PubMed
  9. Curr Opin Neurobiol. 2003 Aug;13(4):487-92 - PubMed
  10. Anesth Analg. 2002 May;94(5):1253-8, table of contents - PubMed
  11. Eur Urol. 2006 Dec;50(6):1299-305 - PubMed
  12. J Urol. 2000 Sep;164(3 Pt 1):676-9 - PubMed
  13. Am J Med. 2001 Feb 19;110 Suppl 3A:6S-12S - PubMed
  14. Curr Opin Neurobiol. 2011 Feb;21(1):52-60 - PubMed
  15. Muscle Nerve. 1999 Sep;22(9):1177-87 - PubMed
  16. Brain Res Rev. 2009 Apr;60(1):267-77 - PubMed
  17. Nat Biotechnol. 2011 Mar;29(3):173-4 - PubMed
  18. Life Sci. 1994;55(13):1017-26 - PubMed
  19. Nat Rev Neurol. 2010 May;6(5):276-87 - PubMed
  20. Expert Rev Neurother. 2011 Jan;11(1):15-27 - PubMed
  21. Pain. 1999 Feb;79(2-3):127-33 - PubMed
  22. Mol Pain. 2010 Dec 17;6:94 - PubMed
  23. Expert Opin Pharmacother. 2003 Dec;4(12):2279-96 - PubMed
  24. J Pharm Pharmacol. 1992 Apr;44(4):361-3 - PubMed
  25. Neuroscience. 1976 Aug;1(4):239-48 - PubMed
  26. J Neurosci. 1998 Nov 1;18(21):8947-59 - PubMed
  27. Anesth Analg. 2011 Jun;112(6):1487-93 - PubMed
  28. Brain Res. 1988 Jul 12;455(2):205-12 - PubMed
  29. Nature. 1996 Jan 18;379(6562):257-62 - PubMed
  30. J Comp Neurol. 1989 Sep 8;287(2):225-37 - PubMed
  31. Pflugers Arch. 2011 May;461(5):499-506 - PubMed
  32. J Pain. 2012 Oct;13(10):921-9 - PubMed
  33. Neuron. 2005 Jan 6;45(1):17-25 - PubMed
  34. Neurotoxicology. 2003 Dec;24(6):895-908 - PubMed
  35. Anesth Analg. 2010 Sep;111(3):784-90 - PubMed
  36. NIDA Res Monogr. 1986;75:406-9 - PubMed
  37. J Neurobiol. 2004 Oct;61(1):3-12 - PubMed
  38. Pain. 2008 May;136(1-2):202-10 - PubMed
  39. J Comp Neurol. 1988 Nov 8;277(2):302-12 - PubMed
  40. N Engl J Med. 2010 Oct 14;363(16):1521-31 - PubMed
  41. J Clin Invest. 2010 Nov;120(11):3773-8 - PubMed
  42. Pain. 2010 Jun;149(3):522-8 - PubMed
  43. Annu Rev Physiol. 2012;74:225-43 - PubMed
  44. Annu Rev Psychol. 2010;61:243-71 - PubMed
  45. J Biol Chem. 2004 Apr 16;279(16):16377-87 - PubMed
  46. J Biol Chem. 2001 Apr 6;276(14 ):11021-30 - PubMed
  47. Nat Rev Neurosci. 2007 Feb;8(2):114-27 - PubMed
  48. Pain Physician. 2008 Mar;11(2 Suppl):S105-20 - PubMed
  49. Anesth Analg. 2008 Jul;107(1):271-81 - PubMed
  50. Neuroscience. 2004;128(3):555-60 - PubMed
  51. J Urol. 2005 May;173(5):1590-4 - PubMed
  52. J Pain. 2011 Sep;12(9):991-1003 - PubMed
  53. Handb Exp Pharmacol. 2009;(194):563-87 - PubMed
  54. Prog Med Chem. 2012;51:57-70 - PubMed
  55. Cell. 2011 Dec 23;147(7):1615-27 - PubMed
  56. J Comp Neurol. 1990 Dec 15;302(3):562-74 - PubMed
  57. Exp Neurol. 1983 Apr;80(1):167-77 - PubMed
  58. J Med Chem. 1994 Jun 24;37(13):1942-54 - PubMed
  59. Mol Pain. 2008 Jan 16;4:3 - PubMed
  60. J Biol Chem. 2001 Aug 17;276(33):31163-70 - PubMed
  61. Peptides. 1989 Sep-Oct;10(5):979-83 - PubMed
  62. J Chem Neuroanat. 2000 Feb;18(1-2):75-86 - PubMed
  63. Eur J Neurosci. 2011 Apr;33(8):1385-400 - PubMed
  64. Curr Top Med Chem. 2011;11(17 ):2171-9 - PubMed
  65. J Physiol. 2007 Jan 1;578(Pt 1):9-24 - PubMed
  66. Nature. 2007 Mar 1;446(7131):24 - PubMed
  67. Expert Opin Ther Pat. 2010 Aug;20(8):1019-45 - PubMed
  68. J Neuropathol Exp Neurol. 2008 Feb;67(2):93-104 - PubMed
  69. J Neurosci. 2012 Jul 11;32(28):9706-15 - PubMed
  70. Pain. 2003 Jul;104(1-2):219-28 - PubMed
  71. Expert Opin Drug Saf. 2007 Nov;6(6):637-40 - PubMed
  72. Anesth Analg. 2007 Sep;105(3):825-31 - PubMed
  73. J Neurosci. 2012 Jun 20;32(25):8686-95 - PubMed
  74. Curr Pain Headache Rep. 2007 Feb;11(1):25-32 - PubMed
  75. J Physiol. 2007 Jan 15;578(Pt 2):481-90 - PubMed
  76. Int Urogynecol J Pelvic Floor Dysfunct. 2005 Jul-Aug;16(4):293-7 - PubMed
  77. J Pain. 2012 Aug;13(8):790-8 - PubMed
  78. Exp Neurol. 2012 May;235(1):316-25 - PubMed
  79. Brain Res. 1981 Apr 6;210(1-2):115-28 - PubMed
  80. J Neurosci. 2003 Jun 15;23(12):4793-7 - PubMed
  81. Pain. 2011 May;152(5):1192-200 - PubMed
  82. EMBO J. 2011 Feb 2;30(3):582-93 - PubMed
  83. Nature. 1997 Oct 23;389(6653):816-24 - PubMed
  84. Pain. 1992 Nov;51(2):175-94 - PubMed
  85. Nat Clin Pract Neurol. 2007 Dec;3(12):648-9 - PubMed
  86. Eur J Neurosci. 1999 Mar;11(3):946-58 - PubMed
  87. J Neurosurg. 2005 Mar;102(3):522-5 - PubMed
  88. Peptides. 2004 Mar;25(3):527-32 - PubMed
  89. Anesth Analg. 2007 May;104(5):1210-6, tables of contents - PubMed
  90. Pain Physician. 2008 Mar-Apr;11(2):215-24 - PubMed

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