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Intrathecal Pharmacology

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Abstract

Intrathecal therapy (IT) is a vital component in the treatment of moderate to severe refractory cancer or noncancer pain. Knowledge and clinical experience using targeted intrathecal drug delivery have continued to grow as evidenced in the writings of the Polyanalgesic Consensus Conference (PACC). The distinguished authors of the PACC guidelines point out that IT is not a salvage therapy for high-dose opioid failure and recommend earlier IT trials for appropriate patient populations. They emphasize that treatment should be based on disease indications with known mechanisms so that appropriate drug selection can take place. Currently, there are only two FDA-approved medications for IT: morphine and ziconotide. Use of other medications such as bupivacaine, clonidine, and baclofen to treat chronic pain states is off-label. This chapter focuses on the pharmacokinetics, pharmacodynamics, and evidence for use of these and other medications in the intrathecal space. Current research continues to explore both new medications and medication combinations with the aim of improving patient safety and sustainable outcomes.

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Recommended Reading

  1. Abrahams M, Higgins P, Whyte P, Breen P, Muttu S, Gardiner J. Intact proprioception and control of labour pain during epidural analgesia. Acta Anaesthesiol Scand. 1999;43(1):46–50.

    Article  CAS  PubMed  Google Scholar 

  2. Åkerman B, Arweström E, Post C. Local anesthetics potentiate spinal morphine Antinociception. Anesthesia & Analgesia. 1988;67(10):943.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. 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.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. Behar M, Magora F, Olshwang D, Davidson JT. Epidural morphine in treatment of pain. Lancet. 1979;1(8115):527–9.

    Article  CAS  PubMed  Google Scholar 

  8. Belverud S, Mogilner A, Schulder M. Intrathecal pumps. Neurotherapeutics. 2008;5(1):114–22.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Google Scholar 

  10. Bernards CM. Understanding the physiology and pharmacology of epidural and intrathecal opioids. Best Pract Res Clin Anaesthesiol. 2002;16(4):489–505.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. Boswell MV, Iacono RP, Guthkelch AN. Sites of action of subarachnoid lidocaine and tetracaine: observations with evoked potential monitoring during spinal cord stimulator implantation. Reg Anesth. 1992;17(1):37–42.

    CAS  PubMed  Google Scholar 

  15. Brill S, Gurman GM, Fisher A. A history of neuraxial administration of local analgesics and opioids. Eur J Anaesthesiol. 2003;20(9):682–9.

    Article  CAS  PubMed  Google Scholar 

  16. Brown DC, Agnello K, Iadarola MJ. Intrathecal resiniferatoxin in a dog model: efficacy in bone cancer pain. Pain. 2015;156(6):1018–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Calthorpe N. The history of spinal needles: getting to the point. Anaesthesia. 2004;59(12):1231–41.

    Article  CAS  PubMed  Google Scholar 

  18. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389(6653):816–24.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Coffey RJ, Owens ML, Broste SK, 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.

    Article  PubMed  Google Scholar 

  21. Cohen SP, Dragovich A. Intrathecal analgesia. Anesthesiol Clin. 2007;25(4):863–82, viii.

    Article  CAS  PubMed  Google Scholar 

  22. Corning JL. Local anaesthesia in general medicine and surgery. D. Appleton; 1886.

    Google Scholar 

  23. Covino BG. The pharmacology of local anesthetic agents. In: Stanley TH, Clayton Petty W, editors. Anesthesiology 1986. Developments in critical care medicine and anesthesiology: Springer Netherlands; 1986. p. 6–10.

    Google Scholar 

  24. Dahm P, Nitescu P, Appelgren L, Curelaru I. Efficacy and technical complications of long-term continuous intraspinal infusions of opioid and/or bupivacaine in refractory nonmalignant pain: a comparison between the epidural and the intrathecal approach with externalized or implanted catheters and infusion pumps. Clin J Pain. 1998;14(1):4–16.

    Article  CAS  PubMed  Google Scholar 

  25. Dahm PO, Nitescu PV, Appelgren LK, Curelaru I. Long-term intrathecal (i.t.) infusion of bupivacaine relieved intractable pain and spasticity in a patient with multiple sclerosis. Eur J Pain. 1998;2(1):81–5.

    Article  CAS  PubMed  Google Scholar 

  26. Deer TR. A critical time for practice change in the pain treatment continuum: we need to reconsider the role of pumps in the patient care algorithm. Pain Med. 2010;11(7):987–9.

    Article  PubMed  Google Scholar 

  27. Deer TR. History of intrathecal drug delivery. In: Atlas of implantable therapies for pain management. New York: Springer; 2011. p. 139–41.

    Chapter  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. Deer TR, Serafini M, Buchser E, Ferrante FM, Hassenbusch SJ. Intrathecal bupivacaine for chronic pain: a review of current knowledge. Neuromodulation. 2002;5(4):196–207.

    Article  PubMed  Google Scholar 

  30. Deer TR, Caraway DL, Kim CK, Dempsey CD, Stewart CD, McNeil KF. Clinical experience with intrathecal bupivacaine in combination with opioid for the treatment of chronic pain related to failed back surgery syndrome and metastatic cancer pain of the spine. Spine J. 2002;2(4):274–8.

    Article  PubMed  Google Scholar 

  31. 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 

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

    Article  PubMed  Google Scholar 

  33. Deer TR, Smith HS, Cousins M, 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 

  34. Deer TR, Prager J, Levy R, 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 464–466.

    Article  PubMed  Google Scholar 

  35. Deer TR, Levy R, Prager J, 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.

    Article  PubMed  Google Scholar 

  36. 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.

    Article  PubMed  Google Scholar 

  37. van Dongen RTM, Crul BJP, 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.

    Article  PubMed  Google Scholar 

  38. Du Pen S, Du Pen A, Hillyer J. Intrathecal hydromorphone for intractable nonmalignant pain: a retrospective study. Pain Med. 2006;7(1):10–5.

    Article  PubMed  Google Scholar 

  39. Duarte RV, Raphael JH, Southall JL, Baker C, Hanu-Cernat D. Intrathecal inflammatory masses: is the yearly opioid dose increase an early indicator? Neuromodulation. 2010;13(2):109–13.

    Article  PubMed  Google Scholar 

  40. Feng X, Zhang F, Dong R, et al. Intrathecal administration of clonidine attenuates spinal neuroimmune activation in a rat model of neuropathic pain with existing hyperalgesia. Eur J Pharmacol. 2009;614(1-3):38–43.

    Article  CAS  PubMed  Google Scholar 

  41. Fukushima S, Takenami T, Yagishita S, Nara Y, Hoka S, Okamoto H. Neurotoxicity of intrathecally administered fentanyl in a rat spinal model. Pain Med. 2011;12(5):717–25.

    Article  PubMed  Google Scholar 

  42. Ghafoor VL, Epshteyn M, Carlson GH, Terhaar DM, Charry O, Phelps PK. Intrathecal drug therapy for long-term pain management. Am J Health Syst Pharm. 2007;64(23):2447–61.

    Article  CAS  PubMed  Google Scholar 

  43. Goldstein A, Lowney LI, Pal BK. Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain. Proc Natl Acad Sci U S A. 1971;68(8):1742–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Greenberg HS, Taren J, Ensminger WD, Doan K. Benefit from and tolerance to continuous intrathecal infusion of morphine for intractable cancer pain. J Neurosurg. 1982;57(3):360–4.

    Article  CAS  PubMed  Google Scholar 

  45. Grider JS, Harned ME, Etscheidt MA. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician. 2011;14(4):343–51.

    PubMed  Google Scholar 

  46. Hayek SM, Hanes MC. Intrathecal therapy for chronic pain: current trends and future needs. Curr Pain Headache Rep. 2014;18(1):388.

    Article  PubMed  Google Scholar 

  47. Hayek SM, Joseph PN, Mekhail NA. Pharmacology of intrathecally administered agents for treatment of spasticity and pain. Seminars in Pain Medicine. 2003;1(4):238–53.

    Article  CAS  Google Scholar 

  48. 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.

    PubMed  Google Scholar 

  49. Hayek SM, Veizi IE, Narouze SN, Mekhail N. Age-dependent intrathecal opioid escalation in chronic noncancer pain patients. Pain Med. 2011;12(8):1179–89.

    Article  PubMed  Google Scholar 

  50. Herz A, Teschemacher HJ. Activities and sites of antinociceptive action of morphine-like analgesics and kinetics of distribution following intravenous, intracerebral and intraventricular application. Adv Drug Res. 1971;6:79–119.

    CAS  Google Scholar 

  51. Hildebrand KR, Elsberry DD, Deer TR. Stability, compatibility, and safety of intrathecal bupivacaine administered chronically via an implantable delivery system. Clin J Pain. 2001;17(3):239–44.

    Article  CAS  PubMed  Google Scholar 

  52. Hoederath P, Gautschi OP, Land M, Hildebrandt G, Fournier JY. Formation of two consecutive intrathecal catheter tip granulomas within nine months. Cent Eur Neurosurg. 2010;71(1):39–42.

    Article  CAS  PubMed  Google Scholar 

  53. Holzer P. The pharmacological challenge to tame the transient receptor potential vanilloid-1 (TRPV1) nocisensor. Br J Pharmacol. 2008;155(8):1145–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hsu Y, Hettiarachchi HDM, Zhu DC, Linninger AA. The frequency and magnitude of cerebrospinal fluid pulsations influence intrathecal drug distribution: key factors for interpatient variability. Anesth Analg. 2012;115(2):386–94.

    Article  CAS  PubMed  Google Scholar 

  55. 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.

    Article  PubMed  Google Scholar 

  56. Karai L, Brown DC, Mannes AJ, et al. Deletion of vanilloid receptor 1_expressing primary afferent neurons for pain control. J Clin Invest. 2004;113(9):1344–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  59. Krames ES, Olson K. Clinical realities and economic considerations: patient selection in intrathecal therapy. J Pain Symptom Manage. 1997;14(3 Suppl):S3–S13.

    Article  CAS  PubMed  Google Scholar 

  60. Krashin DL, Merrill JO, Trescot AM. Opioids in the management of HIV-related pain. Pain Physician. 2012;15(3 Suppl):ES157–68.

    PubMed  Google Scholar 

  61. Kroin JS. Intrathecal drug administration. Clin Pharmacokinet. 1992;22(5):319–26.

    Article  CAS  PubMed  Google Scholar 

  62. 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.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  64. Li DF, Bahar M, Cole G, Rosen M. Neurological toxicity of the subarachnoid infusion of bupivacaine, lignocaine or 2-chloroprocaine in the rat. Br J Anaesth. 1985;57(4):424–9.

    Article  CAS  PubMed  Google Scholar 

  65. Lundborg C, Dahm P, Nitescu P, Biber B. High intrathecal bupivacaine for severe pain in the head and neck. Acta Anaesthesiol Scand. 2009;53(7):908–13.

    Article  CAS  PubMed  Google Scholar 

  66. 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 Technol Neural Interface. 2002;5(4):208–13.

    Article  Google Scholar 

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

    Google Scholar 

  68. Nitescu P, Dahm P, Appelgren L, Curelaru I. Continuous infusion of opioid and bupivacaine by externalized intrathecal catheters in long-term treatment of“ refractory” nonmalignant pain. Clin J Pain. 1998;14(1):17–28.

    Article  CAS  PubMed  Google Scholar 

  69. North RA. Drug receptors and the inhibition of nerve cells. Br J Pharmacol. 1989;98(1):13–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. North RB, Cutchis PN, Epstein JA, Long DM. Spinal cord compression complicating subarachnoid infusion of morphine: case report and laboratory experience. Neurosurgery. 1991;29(5):778–84.

    Article  CAS  PubMed  Google Scholar 

  71. Onofrio BM, Yaksh TL, Arnold PG. Continuous low-dose intrathecal morphine administration in the treatment of chronic pain of malignant origin. Mayo Clin Proc. 1981;56(8):516–20.

    CAS  PubMed  Google Scholar 

  72. Papisov MI, Belov VV, Gannon KS. Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS. Mol Pharm. 2013;10(5):1522–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 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 

  74. Penn RD, Paice JA. Chronic intrathecal morphine for intractable pain. J Neurosurg. 1987;67(2):182–6.

    Article  CAS  PubMed  Google Scholar 

  75. Perruchoud C, Eldabe S, Durrer A, 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.

    Article  PubMed  Google Scholar 

  76. Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissue. Science. 1973;179(4077):1011–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  79. Prager J, Deer T, Levy R, et al. Best practices for intrathecal drug delivery for pain. Neuromodulation. 2014;17(4):354–72; discussion 372.

    Article  PubMed  Google Scholar 

  80. Rainov NG, Heidecke V, Burkert W. Long-term intrathecal infusion of drug combinations for chronic back and leg pain. J Pain Symptom Manage. 2001;22(4):862–71.

    Article  CAS  PubMed  Google Scholar 

  81. Ramsey CN, Owen RD, Witt WO, Grider JS. Intrathecal granuloma in a patient receiving high dose hydromorphone. Pain Physician. 2008;11(3):369–73.

    PubMed  Google Scholar 

  82. Rauck RL, Wallace MS, Leong MS, 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  84. Rennels ML, Blaumanis OR, Grady PA. Rapid solute transport throughout the brain via paravascular fluid pathways. Adv Neurol. 1990;52:431–9.

    CAS  PubMed  Google Scholar 

  85. Resiniferatoxin to Treat Severe Pain Associated with Advanced Cancer – Full Text View – ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT00804154. Accessed 13 Sept 2017.

  86. Saltari MR, Shaladi A, Piva B, et al. The management of pain from collapse of osteoporotic vertebrae with continuous intrathecal morphine infusion. Neuromodulation. 2007;10(2):167–76.

    Article  PubMed  Google Scholar 

  87. Schmidtko A, Lötsch J, Freynhagen R, Geisslinger G. Ziconotide for treatment of severe chronic pain. Lancet. 2010;375(9725):1569–77.

    Article  CAS  PubMed  Google Scholar 

  88. Scott DB, McClure JH, Giasi RM, Seo J, Covino BG. Effects of concentration of local anaesthetic drugs in extradural block. Br J Anaesth. 1980;52(10):1033–7.

    Article  CAS  PubMed  Google Scholar 

  89. Sjoberg M, Nitescu P, Appelgren L, Curelaru L. Long-term intrathecal morphine and bupivacaine in patients with refractory cancer pain-results from a morphine-bupivacaine dose regimen of 0.5/4.75 mg/ml. Anesthesiology. 1994;80(2):284–97.

    Article  CAS  PubMed  Google Scholar 

  90. Staats PS, Yearwood T, Charapata SG, 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.

    Article  CAS  PubMed  Google Scholar 

  91. Stockman HW. Effect of anatomical fine structure on the flow of cerebrospinal fluid in the spinal subarachnoid space. J Biomech Eng. 2006;128(1):106–14.

    Article  PubMed  Google Scholar 

  92. Tobias G, Sands RP Jr, Bacon DR. Continuous spinal anesthesia: a continuous history? Reg Anesth Pain Med. 1999;24(5):453–7.

    CAS  PubMed  Google Scholar 

  93. Tuohy CEB. Costinuous spinal anesthesiaits usefitiisess and technic involved. Anesthesiology. 1944;5(2):142–8.

    Article  Google Scholar 

  94. Uhle EI, Becker R, Gatscher S, Bertalanffy H. Continuous intrathecal clonidine administration for the treatment of neuropathic pain. Stereotact Funct Neurosurg. 2000;75(4):167–75.

    Article  CAS  PubMed  Google Scholar 

  95. Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology. 2000;92(3):739–53.

    Article  CAS  PubMed  Google Scholar 

  96. Van Dongen RT, Crul BJ, De Bock M. Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of cancer pain: a retrospective analysis of 51 cases. Pain. 1993;55(1):119–23.

    Article  PubMed  Google Scholar 

  97. Veizi IE, Hayek SM, Narouze S, Pope JE, Mekhail N. Combination of intrathecal opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer pain patients. Pain Med. 2011;12(10):1481–9.

    Article  PubMed  Google Scholar 

  98. Waara-Wolleat KL, Hildebrand KR, Stewart GR. A review of intrathecal fentanyl and Sufentanil for the treatment of chronic pain. Pain Med. 2006;7(3):251–9.

    Article  PubMed  Google Scholar 

  99. Wagemans MF, van der Valk P, Spoelder EM, Zuurmond WW, de Lange JJ. Neurohistopathological findings after continuous intrathecal administration of morphine or a morphine/bupivacaine mixture in cancer pain patients. Acta Anaesthesiol Scand. 1997;41(8):1033–8.

    Article  CAS  PubMed  Google Scholar 

  100. Wallace MS, Charapata SG, Fisher R, 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.

    Article  PubMed  Google Scholar 

  101. Wallace MS, Rauck R, Fisher R, et al. Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial. Anesth Analg. 2008;106(2):628–37, table of contents.

    Article  CAS  PubMed  Google Scholar 

  102. Wallace MS, Kosek PS, Staats P, Fisher R, Schultz DM, Leong M. Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain. Pain Med. 2008;9(3):271–81.

    Article  PubMed  Google Scholar 

  103. 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.

    Article  PubMed  Google Scholar 

  104. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  106. Wermeling D, Drass M, Ellis D, et al. Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients. J Clin Pharmacol. 2003;43(6):624–36.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  108. Yaksh TL, Jessell TM, Gamse R, Mudge AW, Leeman SE. Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature. 1980;286(5769):155–7.

    Article  CAS  PubMed  Google Scholar 

  109. Yaksh TL, Horais KA, Tozier NA, et al. Chronically infused intrathecal morphine in dogs. Anesthesiology. 2003;99(1):174–87.

    Article  CAS  PubMed  Google Scholar 

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Campos, L.W. (2019). Intrathecal Pharmacology. In: Deer, T., Pope, J., Lamer, T., Provenzano, D. (eds) Deer's Treatment of Pain. Springer, Cham. https://doi.org/10.1007/978-3-030-12281-2_79

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