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Intrathecal Therapy for the Treatment of Pain in the Rehabilitation Patient

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Comprehensive Pain Management in the Rehabilitation Patient

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Abstract

Intrathecal therapy (ITT) is a vital component of the multimodal pain practice and is gaining positive attention for sustainable outcomes and cost effectiveness. Not unlike other pain care therapies, ITT requires vigilance, which should be focused on implementation and patient selection. In this chapter, we explore recent insights on the pharmacokinetics of the intrathecal space, the impact on device selection, strategies surrounding catheter placement, and insights into future directions.

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References

  1. Yaksh TL, Rudy TA. Analgesia mediated by a direct spinal action of narcotics. Science. 1976;192(4246):1357–8.

    CAS  PubMed  Google Scholar 

  2. Belverud S, Mogilner A, Schulder M. Intrathecal pumps. Neurotherapeutics. Elsevier2008;5(1):114–22.

    PubMed  PubMed Central  Google Scholar 

  3. Krames ES. Intrathecal infusional therapies for intractable pain: patient management guidelines. J Pain Symptom Manage. 1993;8(1):36–46.

    CAS  PubMed  Google Scholar 

  4. Hayek SM, Deer TR, Pope JE, Panchal SJ, Patel VB. Intrathecal therapy for cancer and non-cancer pain. Pain Physician. 2011;14(3):219–48. kalbemed.com

    PubMed  Google Scholar 

  5. Bernards CM. Cerebrospinal fluid and spinal cord distribution of baclofen and bupivacaine during slow intrathecal infusion in pigs. Anesthesiology. 2006;105(1):169–78.

    PubMed  Google Scholar 

  6. Yaksh TL, de Kater A, Dean R, Best BM, Miljanich GP. Pharmacokinetic analysis of ziconotide (SNX-111), an intrathecal N-type calcium channel blocking analgesic, delivered by bolus and infusion in the dog. Neuromodulation. 2012;15(6):508–19. discussion 519

    PubMed  PubMed Central  Google Scholar 

  7. Deer TR, Prager J, Levy R, Rathmell J, Buchser E, Burton A, et al. Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation. 2012;15(5):436–64. discussion 464–6

    PubMed  Google Scholar 

  8. Coffey RJ, Owens ML, Broste SK, Dubois MY, Ferrante FM, Schultz DM, et al. Medical practice perspective: identification and mitigation of risk factors for mortality associated with intrathecal opioids for non-cancer pain. Pain Med. 2010;11(7):1001–9.

    PubMed  Google Scholar 

  9. Attal N, Bouhassira D. Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain. 2015;156(Suppl 1):S104–14.

    PubMed  Google Scholar 

  10. Coffey RJ, Owens ML, Broste SK, Dubois MY, Ferrante FM, Schultz DM, et al. Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain. Anesthesiology. 2009;111(4):881–91.

    PubMed  Google Scholar 

  11. Deer TR, Pope JE. Factors to consider in the choice of intrathecal drug in the treatment of neuropathic pain. Expert Rev Clin Pharmacol. 2015;8(5):507–10.

    CAS  PubMed  Google Scholar 

  12. Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):4040–9.

    CAS  PubMed  Google Scholar 

  13. Pope JE, Deer TR. Intrathecal pharmacology update: novel dosing strategy for intrathecal monotherapy ziconotide on efficacy and sustainability. Neuromodulation. 2015;18(5):414–20.

    PubMed  Google Scholar 

  14. Rauck RL, Wallace MS, Leong MS, Minehart M, Webster LR, Charapata SG, et al. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manage. 2006;31(5):393–406.

    CAS  PubMed  Google Scholar 

  15. Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291(1):63–70.

    CAS  PubMed  Google Scholar 

  16. Wallace MS, Charapata SG, Fisher R, Byas-Smith M, Staats PS, Mayo M, et al. Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial. Neuromodulation. 2006;9(2):75–86.

    PubMed  Google Scholar 

  17. Patel VB, Manchikanti L, Singh V, Schultz DM, Hayek SM, Smith HS. Systematic review of intrathecal infusion systems for long-term management of chronic non-cancer pain. Pain Physician. 2009;12(2):345–60.

    PubMed  Google Scholar 

  18. Deer TR, Kim C, Bowman R, Tolentino D, Stewart C, Tolentino W. Intrathecal ziconotide and opioid combination therapy for noncancer pain: an observational study. Pain Physician. 2009;12(4):E291–6.

    PubMed  Google Scholar 

  19. McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3(1):69–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lawson EF, Wallace MS. Current developments in intraspinal agents for cancer and noncancer pain. Curr Pain Headache Rep. 2010;14(1):8–16.

    PubMed  PubMed Central  Google Scholar 

  21. Bernards CM. Recent insights into the pharmacokinetics of spinal opioids and the relevance to opioid selection. Curr Opin Anaesthesiol. 2004;17(5):441–7.

    PubMed  Google Scholar 

  22. Bernards CM, Shen DD, Sterling ES, Adkins JE, Risler L, Phillips B, et al. Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids. Anesthesiology. 2003;99(2):455–65.

    CAS  PubMed  Google Scholar 

  23. Mironer YE, Haasis JC, Chapple I, Brown C, Satterthwaite JR. Efficacy and safety of intrathecal opioid/bupivacaine mixture in chronic nonmalignant pain: a double blind, randomized, crossover, multicenter study by the national forum of independent pain clinicians (NFIPC). Neuromodulation. 2002;5(4):208–13.

    PubMed  Google Scholar 

  24. van Dongen RT, Crul BJ, van Egmond J. Intrathecal coadministration of bupivacaine diminishes morphine dose progression during long-term intrathecal infusion in cancer patients. Clin J Pain. 1999;15(3):166–72.

    PubMed  Google Scholar 

  25. Saito Y, Kaneko M, Kirihara Y, Sakura S, Kosaka Y. Interaction of intrathecally infused morphine and lidocaine in rats (part I): synergistic antinociceptive effects. Anesthesiology. 1998;89(6):1455–63.

    CAS  PubMed  Google Scholar 

  26. Kumar K, Bodani V, Bishop S, Tracey S. Use of intrathecal bupivacaine in refractory chronic nonmalignant pain. Pain Med. 2009;10(5):819–28.

    PubMed  Google Scholar 

  27. Pope JE, Deer TR. Ziconotide: a clinical update and pharmacologic review. Expert Opin Pharmacother. 2013;14(7):957–66.

    CAS  PubMed  Google Scholar 

  28. Webster LR, Fakata KL, Charapata S, Fisher R, MineHart M. Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of morphine in patients receiving ziconotide for severe chronic pain. Pain Med. 2008;9(3):282–90.

    PubMed  Google Scholar 

  29. Wermeling DP. Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain. Pharmacotherapy. 2005;25(8):1084–94.

    CAS  PubMed  Google Scholar 

  30. Pope JE, Deer TR, Bruel BM, Falowski S. Clinical uses of intrathecal therapy and its placement in the pain care algorithm. Pain Pract. 2016. doi:10.1111/papr.12438.

  31. Yaksh TL, Horais KA, Tozier NA, Allen JW, Rathbun M, Rossi SS, et al. Chronically infused intrathecal morphine in dogs. Anesthesiology. 2003;99(1):174–87.

    CAS  PubMed  Google Scholar 

  32. Atli A, Theodore BR, Turk DC, Loeser JD. Intrathecal opioid therapy for chronic nonmalignant pain: a retrospective cohort study with 3-year follow-up. Pain Med. 2010;11(7):1010–6.

    PubMed  Google Scholar 

  33. Berg A, Barsa J, Deer T, Dunbar E, Dwarakanath G, Padda G, et al. Efficacy of morphine sulfate infusion via the Prometra® intrathecal infusion pump. A prospective multicenter evaluation. In: 5th World Congress Institute of Pain; 2009.

    Google Scholar 

  34. Kongkam P, Wagner DL, Sherman S, Fogel EL, Whittaker SC, Watkins JL, et al. Intrathecal narcotic infusion pumps for intractable pain of chronic pancreatitis: a pilot series. Am J Gastroenterol. 2009;104(5):1249–55.

    PubMed  Google Scholar 

  35. Saltari MR, Shaladi A, Piva B, Gilli G, Tartari S, Dall’ara R, et al. The management of pain from collapse of osteoporotic vertebrae with continuous intrathecal morphine infusion. Neuromodulation. 2007;10(2):167–76.

    PubMed  Google Scholar 

  36. Reig E, Abejón D. Continuous morphine infusion: a retrospective study of efficacy, safety, and demographic variables. Neuromodulation. 2009;12(2):122–9.

    PubMed  Google Scholar 

  37. Netter FH. Atlas of human anatomy. Elsevier Health Sciences; 2010.

    Google Scholar 

  38. Artru AA. CSF dynamics, cerebral edema and intracranial pressure. In: Textbook of neuroanesthesia: with neurosurgical and neuroscience perspectives. New York: McGraw-Hill; 1997. p. 61–115.

    Google Scholar 

  39. Balédent O, Henry-Feugeas MC, Idy-Peretti I. Cerebrospinal fluid dynamics and relation with blood flow: a magnetic resonance study with semiautomated cerebrospinal fluid segmentation. Invest Radiol. 2001;36(7):368–77.

    PubMed  Google Scholar 

  40. Bhadelia RA, Bogdan AR, Kaplan RF, Wolpert SM. Cerebrospinal fluid pulsation amplitude and its quantitative relationship to cerebral blood flow pulsations: a phase-contrast MR flow imaging study. Neuroradiology. 1997;39(4):258–64.

    CAS  PubMed  Google Scholar 

  41. Dominguez E, Sahinler B, Bassam D, Day M, Lou L, Racz G, et al. Predictive value of intrathecal narcotic trials for long-term therapy with implantable drug administration systems in chronic non-cancer pain patients. Pain Pract. 2002;2(4):315–25.

    PubMed  Google Scholar 

  42. Huang KT, Martin J, Marky A, Chagoya G, Hatef J, Hazzard MA, et al. A national survey of spinal cord stimulation trial-to-permanent conversion rates. Neuromodulation. 2015;18(2):133–9. discussion 139–40

    PubMed  Google Scholar 

  43. Mohammed SI, Eldabe S, Simpson KH, Brookes M, Madzinga G, Gulve A, et al. Bolus intrathecal injection of ziconotide (Prialt®) to evaluate the option of continuous administration via an implanted intrathecal drug delivery (ITDD) system: a pilot study. Neuromodulation. 2013;16(6):576–81. discussion 582

    PubMed  Google Scholar 

  44. Burton AW, Deer TR, Wallace MS, Rauck RL, Grigsby E. Considerations and methodology for trialing ziconotide. Pain Physician. 2010;13(1):23–33.

    PubMed  Google Scholar 

  45. Anderson VC, Burchiel KJ, Cooke B. A prospective, randomized trial of intrathecal injection vs. epidural infusion in the selection of patients for continuous intrathecal opioid therapy. Neuromodulation. 2003;6(3):142–52.

    PubMed  Google Scholar 

  46. Deer TR, Smith HS, Cousins M, Doleys DM, Levy RM, Rathmell JP, et al. Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery. Pain Physician. 2010;13(3):E175–213.

    PubMed  Google Scholar 

  47. Duarte R, Raphael J, Eldabe S. Intrathecal drug delivery for the management of pain and spasticity in adults: an executive summary of the British Pain Society’s recommendations for best clinical practice. Br J Pain. 2016;10(2):67–9.

    Google Scholar 

  48. Battal B, Kocaoglu M, Bulakbasi N, Husmen G, Tuba Sanal H, Tayfun C. Cerebrospinal fluid flow imaging by using phase-contrast MR technique. Br J Radiol. 2011;84(1004):758–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Bulat M, Klarica M. Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev. 2011;65(2):99–112.

    PubMed  Google Scholar 

  50. Friese S, Hamhaber U, Erb M, Kueker W, Klose U. The influence of pulse and respiration on spinal cerebrospinal fluid pulsation. Invest Radiol. 2004;39(2):120–30.

    PubMed  Google Scholar 

  51. Deer TR, Levy R, Prager J, Buchser E, Burton A, Caraway D, et al. Polyanalgesic Consensus Conference--2012: recommendations to reduce morbidity and mortality in intrathecal drug delivery in the treatment of chronic pain. Neuromodulation. 2012;15(5):467–82. discussion 482

    PubMed  Google Scholar 

  52. Coffey RJ, Burchiel K. Inflammatory mass lesions associated with intrathecal drug infusion catheters: report and observations on 41 patients. Neurosurgery. 2002;50(1):78–86. discussion 86–7

    PubMed  Google Scholar 

  53. Shields DC, Palma C, Khoo LT, Ferrante FM. Extramedullary intrathecal catheter granuloma adherent to the conus medullaris presenting as cauda equina syndrome. Anesthesiology. 2005;102(5):1059–61.

    PubMed  Google Scholar 

  54. Johansen MJ, Satterfield WC, Baze WB, Hildebrand KR, Gradert TL, Hassenbusch SJ. Continuous intrathecal infusion of hydromorphone: safety in the sheep model and clinical implications. Pain Med. 2004;5(1):14–25.

    PubMed  Google Scholar 

  55. Yaksh TL, Hassenbusch S, Burchiel K, Hildebrand KR, Page LM, Coffey RJ. Inflammatory masses associated with intrathecal drug infusion: a review of preclinical evidence and human data. Pain Med. 2002;3(4):300–12.

    PubMed  Google Scholar 

  56. Zacest AC, Carlson JD, Nemecek A, Burchiel KJ. Surgical management of spinal catheter granulomas: operative nuances and review of the surgical literature. Neurosurgery. 2009;65(6):1161–4. discussion 1164–5

    PubMed  Google Scholar 

  57. Allen JW, Horais KA, Tozier NA, Yaksh TL. Opiate pharmacology of intrathecal granulomas. Anesthesiology. 2006;105(3):590–8.

    CAS  PubMed  Google Scholar 

  58. Deer TR. A prospective analysis of intrathecal granuloma in chronic pain patients: a review of the literature and report of a surveillance study. Pain Physician. 2004;7(2):225–8.

    PubMed  Google Scholar 

  59. Perruchoud C, Eldabe S, Durrer A, Bovy M, Brookes M, Madzinga G, et al. Effects of flow rate modifications on reported analgesia and quality of life in chronic pain patients treated with continuous intrathecal drug therapy. Pain Med. 2011;12(4):571–6.

    PubMed  Google Scholar 

  60. van der Plas AA, Marinus J, Eldabe S, Buchser E, van Hilten JJ. The lack of efficacy of different infusion rates of intrathecal baclofen in complex regional pain syndrome: a randomized, double-blind, crossover study. Pain Med. 2011;12(3):459–65.

    PubMed  Google Scholar 

  61. Rauck R, Deer T, Rosen S, Padda G, Barsa J, Dunbar E, et al. Accuracy and efficacy of intrathecal administration of morphine sulfate for treatment of intractable pain using the Prometra(®) Programmable Pump. Neuromodulation. 2010;13(2):102–8.

    PubMed  Google Scholar 

  62. Webster LR, Fisher R, Charapata S, Wallace MS. Long-term intrathecal ziconotide for chronic pain: an open-label study. J Pain Symptom Manage. 2009;37(3):363–72.

    CAS  PubMed  Google Scholar 

  63. Deer TR, Krames E, Levy RM, Hassenbusch 3rd SJ, Prager JP. Practice choices and challenges in the current intrathecal therapy environment: an online survey. Pain Med. 2009;10(2):304–9.

    Google Scholar 

  64. Kumar K, Hunter G, Demeria DD. Treatment of chronic pain by using intrathecal drug therapy compared with conventional pain therapies: a cost-effectiveness analysis. J Neurosurg. 2002;97(4):803–10. thejns.org

    PubMed  Google Scholar 

  65. Manchikanti L, Kaye AM, Kaye AD. Current state of opioid therapy and abuse. Curr Pain Headache Rep. 2016;20(5):34.

    PubMed  Google Scholar 

  66. Shortreed SM, Peeters A, Forbes AB. Estimating the effect of long-term physical activity on cardiovascular disease and mortality: evidence from the Framingham Heart Study. Heart. 2013;99(9):649–54.

    PubMed  Google Scholar 

Recommended Reading

  • Deer TR, Caraway DL, Wallace MS. A definition of refractory pain to help determine suitability for device implantation. Neuromodulation. 2014;17:711–5.

    PubMed  Google Scholar 

  • Pope JE, Deer TR, McRoberts WP. Intrathecal therapy: the burden of being positioned as a salvage therapy. Pain Med. 2015. doi:10.1111/pme.12782.

  • Deer TR, Pope JE. Factors to consider in the choice of intrathecal drug in the treatment of neuropathic pain. Expert Rev. Clin Pharmacol. 2015;8(5):507–10.

    CAS  PubMed  Google Scholar 

  • Pope JE, Deer TR. Intrathecal pharmacology update: novel dosing strategy for intrathecal therapy and monotherapy ziconotide. Neuromodulation. 2015;18(5):414–20. doi:10.1111/ner.12274. Epub 2015 Feb 24

    Article  PubMed  Google Scholar 

  • Fitzgibbon DR, Stephens LS, Posner KL, et al. INjruy and liability associated with implantable devices for chronic pain. Anesthesiology. 2016;124:00–0.

    Google Scholar 

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Authors and Affiliations

  1. Summit Pain Alliance, Santa Rosa, CA, USA

    Lucas W. Campos M.D., Ph.D. & Jason E. Pope M.D., D.A.B.P.M., F.I.P.P.

  2. Center for Pain Relief, Inc., 400 Court Street, Suite 100, Charleston, WV, 25301, USA

    Timothy R. Deer M.D.

Authors
  1. Lucas W. Campos M.D., Ph.D.
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  2. Jason E. Pope M.D., D.A.B.P.M., F.I.P.P.
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  3. Timothy R. Deer M.D.
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Correspondence to Jason E. Pope M.D., D.A.B.P.M., F.I.P.P. .

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Editors and Affiliations

  1. Department of Neurosurgery, Brown University, Warren Alpert Medical School, Providence, USA

    Alexios Carayannopoulos DO, MPH

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Campos, L.W., Pope, J.E., Deer, T.R. (2017). Intrathecal Therapy for the Treatment of Pain in the Rehabilitation Patient. In: Carayannopoulos DO, MPH, A. (eds) Comprehensive Pain Management in the Rehabilitation Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-16784-8_56

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  • DOI: https://doi.org/10.1007/978-3-319-16784-8_56

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