Intrathecal Therapy for Chronic Pain: Current Trends and Future Needs

Anesthetic Techniques in Pain Management (D Wang, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Anesthetic Techniques in Pain Management

Abstract

The management of chronic pain continues to pose many challenges to healthcare providers. Intrathecal drug delivery systems (IDDS) provide an effective therapy for patients suffering from chronic pain intractable to medical management. However, the clinical growth of intrathecal therapy continues to face many challenges, and is likely underutilized secondary to its high-complexity and limited reimbursement. The clinical utility of IDDS remains limited by lack of prospective randomized, placebo-controlled studies. In addition, there remains a need to enhance physician knowledge on the pharmacodynamics and pharmacokinetics of intrathecal drug delivery and promote further research into this field and drug delivery modalities. The purpose of this article is to provide a comprehensive review of the determinants of successful intrathecal drug delivery with an emphasis on its use in noncancer pain.

Keywords

Noncancer pain Opioid tolerance Microdosing Complications Indications Trialing Mechanism of action 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bier A. Atempts over Cocainisirung of the Ruckenmarkers [in German]. Deutsche Zeitschrift für Chirurgie. 1899;51:9.CrossRefGoogle Scholar
  2. 2.
    Kitagawa O. On spinal anesthesia with cocaine. Jpn Soc Surg. 1901;3:185–91.Google Scholar
  3. 3.
    Knight KH, Brand FM, McHaourab AS, Veneziano G. Implantable intrathecal pumps for chronic pain: highlights and updates. Croat Med J. 2007;48:22–34.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Yaksh TL, Wilson PR, Kaiko RF, Inturrisi CE. Analgesia produced by a spinal action of morphine and effects upon parturition in the rat. Anesthesiology. 1979;51:386–92.PubMedCrossRefGoogle Scholar
  5. 5.
    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;68:1742–7.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissue. Science. 1973;179:1011–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979;50:149–51.PubMedCrossRefGoogle Scholar
  8. 8.
    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;56:516–20.PubMedGoogle Scholar
  9. 9.
    Coombs DW, Saunders RL, Gaylor MS, Block AR, Colton T, Harbaugh R, et al. Relief of continuous chronic pain by intraspinal narcotics infusion via an implanted reservoir. JAMA. 1983;250:2336–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Auld AW, Maki-Jokela A, Murdoch DM. Intraspinal narcotic analgesia in the treatment of chronic pain. Spine. 1985;10:777–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Paice JA, Penn RD, Shott S. Intraspinal morphine for chronic pain: a retrospective, multicenter study. J Pain Symptom Manage. 1996;11:71–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Penn RD, Paice JA. Chronic intrathecal morphine for intractable pain. J Neurosurg. 1987;67:182–6. doi:10.3171/jns.1987.67.2.0182.PubMedCrossRefGoogle Scholar
  13. 13.
    Henry-Feugeas MC, Idy-Peretti I, Baledent O, Poncelet-Didon A, Zannoli G, Bittoun J, et al. Origin of subarachnoid cerebrospinal fluid pulsations: a phase-contrast MR analysis. Magn Reson Imaging. 2000;18:387–95.PubMedCrossRefGoogle Scholar
  14. 14.
    Friese S, Hamhaber U, Erb M, Kueker W, Klose U. The influence of pulse and respiration on spinal cerebrospinal fluid pulsation. Invest Radiol. 2004;39:120–30. doi:10.1097/01.rli.0000112089.66448.bd.PubMedCrossRefGoogle Scholar
  15. 15.
    Alperin N, Vikingstad EM, Gomez-Anson B, Levin DN. Hemodynamically independent analysis of cerebrospinal fluid and brain motion observed with dynamic phase contrast MRI. Magn Reson Med. 1996;35:741–54.PubMedCrossRefGoogle Scholar
  16. 16.
    Stockman HW. Effect of anatomical fine structure on the flow of cerebropsinal fluid in the spinal subarachnoid space. J Biochem Eng. 2006;128:106–14.Google Scholar
  17. 17.
    Degrell I, Nagy E. Concentration gradients for HVA, 5-HIAA, ascorbic acid, and uric acid in cerebrospinal fluid. Biol Psychiatry. 1990;27:891–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Bernards CM. Cerebrospinal fluid and spinal cord distribution of baclofen and bupivacaine during slow intrathecal infusion in pigs. Anesthesiology. 2006;105:169–78.PubMedCrossRefGoogle Scholar
  19. 19.•
    Hettiarachchi HD, Hsu Y, Harris Jr TJ, Penn R, Linninger AA, Hettiarachchi HD, et al. The effect of pulsatile flow on intrathecal drug delivery in the spinal canal. Ann Biomed Eng. 2011;39. A study that analyzed cerebrospinal fluid flow patterns using single photon emission computed tomography in a human spine model as a predictor for the deliveery patterns of intrathecal drugs. Google Scholar
  20. 20.
    Bernards CM. Understanding the physiology and pharmacology of epidural and intrathecal opioids. Best Pract Res Clin Anaesthesiol. 2002;16:489–505.PubMedCrossRefGoogle Scholar
  21. 21.
    Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology. 2000;92:739–53.PubMedCrossRefGoogle Scholar
  22. 22.
    McQuay HJ, Sullivan AF, Smallman K, Dickenson AH. Intrathecal opioids, potency and lipophilicity. Pain. 1989;36:111–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Hayek SM, Joseph PN, Mekhail NA. Pharmacology of intrathecally administered agents for treatment of spasticity and pain. Semin Pain Med. 2003;1:238–53. doi:10.1016/j.spmd.2004.02.002.CrossRefGoogle Scholar
  24. 24.
    Herz AT H. Activities and sites of antinociceptive action of morphine-like analgesics and kinetics of distribution following intravenous, intracerebral and intraventricular application. In: Simmonds, editor. Advances in Drug Research. London: Academic Press; 1971. p. p. 739–53.Google Scholar
  25. 25.
    Bernards CM. Recent insights into the pharmacokinetics of spinal opioids and the relevance to opioid selection. Curr Opin Anaesthesiol. 2004;17:441–7.PubMedCrossRefGoogle Scholar
  26. 26.••
    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;15:436–64. doi:10.1111/j.1525-1403.2012.00476.x. Recommendations on proper management of intrathecal drug delivery systems developed by an expert panel.PubMedCrossRefGoogle Scholar
  27. 27.
    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;111:881–91. doi:10.1097/ALN.0b013e3181b64ab8.PubMedCrossRefGoogle Scholar
  28. 28.
    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 noncancer pain. Pain Med. 2010;11:1001–9. doi:10.1111/j.1526-4637.2010.00889.x.PubMedCrossRefGoogle Scholar
  29. 29.•
    Hayek SM, Veizi IE, Narouze SN, Mekhail N. Age-dependent intrathecal opioid escalation in chronic noncancer pain patients. Pain Med. 2011;12:1179–89. doi:10.1111/j.1526-4637.2011.01188.x.PubMedCrossRefGoogle Scholar
  30. 30.
    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;12:1481–9. doi:10.1111/j.1526-4637.2011.01232.x.PubMedCrossRefGoogle Scholar
  31. 31.
    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 noncancer pain patients. Pain Pract. 2002;2:315–25. doi:10.1046/j.1533-2500.2002.02040.x.PubMedCrossRefGoogle Scholar
  32. 32.
    Grider JSH, Etscheidt MA. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician. 2011;14:343–51.PubMedGoogle Scholar
  33. 33.•
    Hamza M, Doleys D, Wells M, Weisbein J, Hoff J, Martin M. A prospective study evaluating the efficacy of opioid cessation and the use of low-dose intrathecal opioid management of noncancer pain.Google Scholar
  34. 34.
    Deer T, Krames ES, Hassenbusch S, Burton A, Caraway D, Dupen S, et al. Management of Intrathecal Catheter-Tip Inflammatory Masses: an updated 2007 consensus statement from an expert panel. Neuromodulation. 2008;11:77–91. doi:10.1111/j.1525-1403.2008.00147.x.PubMedCrossRefGoogle Scholar
  35. 35.
    Allen JW, Horais KA, Tozier NA, Wegner K, Corbeil JA, Mattrey RF, et al. Time course and role of morphine dose and concentration in intrathecal granuloma formation in dogs: a combined magnetic resonance imaging and histopathology investigation. Anesthesiology. 2006;105:581–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Deer TR, Prager J, Levy R, Rathmell J, Buchser E, Burton A, et al. Polyanalgesic Consensus Conference — 2012: consensus on diagnosis, detection, and treatment of catheter-tip granulomas (inflammatory masses). Neuromodulation. 2012;15:483–95. doi:10.1111/j.1525-1403.2012.00449.x. discussion 96.PubMedCrossRefGoogle Scholar
  37. 37.
    Tomycz ND, Ortiz V, McFadden KA, Urgo L, Moossy JJ. Management of symptomatic intrathecal catheter-associated inflammatory masses. Clin Neurol Neurosurg. 2012;114:190–5.Google Scholar
  38. 38.
    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;17:37–42.PubMedGoogle Scholar
  39. 39.
    Tejwani GA, Rattan AK, McDonald JS. Role of spinal opioid receptors in the antinociceptive interactions between intrathecal morphine and bupivacaine. Anesth Analg. 1992;74:726–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Penning JP, Yaksh TL. Interaction of intrathecal morphine with bupivacaine and lidocaine in the rat. Anesthesiology. 1992;77:1186–2000.PubMedCrossRefGoogle Scholar
  41. 41.
    Ortner CM, Posch M, Roessler B, Faybik P, Rutzler K, Grabovica J, et al. On the ropivacaine-reducing effect of low-dose sufentanil in intrathecal labor analgesia. Acta Anaesthesiol Scand. 2010;54:1000–6. doi:10.1111/j.1399-6576.2010.02254.x.PubMedCrossRefGoogle Scholar
  42. 42.
    Parpaglioni R, Baldassini B, Barbati G, Celleno D. Adding sufentanil to levobupivacaine or ropivacaine intrathecal anaesthesia affects the minimum local anaesthetic dose required. Acta Anaesthesiol Scand. 2009;53:1214–20. doi:10.1111/j.1399-6576.2009.02033.x.PubMedCrossRefGoogle Scholar
  43. 43.
    Levin A, Datta S, Camann WR. Intrathecal ropivacaine for labor analgesia: a comparison with bupivacaine. Anesth Analg. 1998;87:624–7.PubMedGoogle Scholar
  44. 44.
    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;15:166–72.PubMedCrossRefGoogle Scholar
  45. 45.
    Mironer YE, Haasis JC, Chapple I, Brown C, Satterthwaite JR. Efficacy and safety of intrathecal opioids/bupivacaine mixture in chronic nonmalignant pain: a double blind, randomized, crossover, multicenter study by the National Forum of Independent Pain Clinicians (NFIPC). Neuromodulation. 2002;5:208–13.PubMedCrossRefGoogle Scholar
  46. 46.
    Zhong Z, Qulian G, Yuan Z, Wangyuan Z, Zhihua S. Repeated intrathecal administration of ropivacaine causes neurotoxicity in rats. Anaesth Intensive Care. 2009;37:929–36.PubMedGoogle Scholar
  47. 47.
    Malinovsky JM, Charles F, Baudrimont M, Pereon Y, Le Corre P, Pinaud M, et al. Intrathecal ropivacaine in rabbits: pharmacodynamic and neurotoxicologic study. Anesthesiology. 2002;97:429–35.PubMedCrossRefGoogle Scholar
  48. 48.
    Yamashita A, Matsumoto M, Matsumoto S, Itoh M, Kawai K, Sakabe T. A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits. Anesth Analg. 2003;97:512–9. table of contents.PubMedCrossRefGoogle Scholar
  49. 49.
    Sjoberg M, Nitescu P, Appelgren L, Curelaru I. 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;80:284–97.PubMedCrossRefGoogle Scholar
  50. 50.
    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;14:17–28.PubMedCrossRefGoogle Scholar
  51. 51.
    McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3:69–85.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Wermeling D, Drass M, Ellis D, Mayo M, McGuire D, O'Connell D, et al. Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients. J Clin Pharmacol. 2003;43:624–36.PubMedGoogle Scholar
  53. 53.
    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;291:63–70. doi:10.1001/jama.291.1.63.PubMedCrossRefGoogle Scholar
  54. 54.
    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;9:75–86. doi:10.1111/j.1525-1403.2006.00055.x.PubMedCrossRefGoogle Scholar
  55. 55.
    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;31:393–406. doi:10.1016/j.jpainsymman.2005.10.003.PubMedCrossRefGoogle Scholar
  56. 56.
    Wallace MS, Rauck R, Fisher R, Charapata SG, Ellis D, Dissanayake S. Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial. Anesth Analg. 2008;106:628–37. doi:10.1213/ane.0b013e3181606fad.PubMedCrossRefGoogle Scholar
  57. 57.
    Maier C, Gockel HH, Gruhn K, Krumova EK, Edel MA. Increased risk of suicide under intrathecal ziconotide treatment? - a warning. Pain. 2011;152:235–7. doi:10.1016/j.pain.2010.10.007.PubMedCrossRefGoogle Scholar
  58. 58.
    Feng X, Zhang F, Dong R, Li W, Liu J, Zhao X, et al. Intrathecal administration of clonidine attenuates spinal neuroimmune activation in a rat model of neuropathic pain with existing hyperalgesia. Eur J Pharmacol. 2009;614:38–43. doi:10.1016/j.ejphar.2009.04.044.PubMedCrossRefGoogle Scholar
  59. 59.
    Yaksh TL, Rathbun M, Jage J, Mirzai T, Grafe M, Hiles RA. Pharacology and toxicology of chronically infused epidural clonidine.HCl in dogs. Fundam Appl Toxicol. 1994;23:319–35.PubMedCrossRefGoogle Scholar
  60. 60.
    Yaksh TL, Horais KA, Tozier NA, Allen JW, Rathbun M, Rossi SS, et al. Chronically infused intrathecal morphine in dogs. Anesthesiology. 2003;99:174–87.PubMedCrossRefGoogle Scholar
  61. 61.
    Bevacqua BK, Fattouh M, Backonja M. Depression, night terrors, and insomnia associated with long-term intrathecal clonidine therapy. Pain Pract. 2007;7:36–8. doi:10.1111/j.1533-2500.2007.00108.x.PubMedCrossRefGoogle Scholar
  62. 62.
    Belverud S, Mogilner A, Schulder M. Intrathecal pumps. Neurotherapeutics. 2008;5:114–22. doi:10.1016/j.nurt.2007.10.070.PubMedCrossRefGoogle Scholar
  63. 63.
    Gerber HR. Intrathecal morphine for chronic benign pain. Best Pract Res Clin Anaesthesiol. 2003;17:429–42.PubMedCrossRefGoogle Scholar
  64. 64.
    Turner JA, Sears JM, Loeser JD. Programmable intrathecal opioid delivery systems for chronic noncancer pain: a systematic review of effectiveness and complications. Clin J Pain. 2007;23:180–95. doi:10.1097/01.ajp.0000210955.93878.44.PubMedCrossRefGoogle Scholar
  65. 65.
    Brown J, Klapow J, Doleys D, Lowery D, Tutak U. Disease-specific and generic health outcomes: a model for the evaluation of long-term intrathecal opioid therapy in noncancer low back pain patients. Clin J Pain. 1999;15:122–31.PubMedCrossRefGoogle Scholar
  66. 66.
    Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994;330:592–6. doi:10.1056/NEJM199403033300902.PubMedCrossRefGoogle Scholar
  67. 67.
    Rauck RL, Cherry D, Boyer MF, Kosek P, Dunn J, Alo K. Long-term intrathecal opioid therapy with a patient-activated, implanted delivery system for the treatment of refractory cancer pain. J Pain. 2003;4:441–7.PubMedCrossRefGoogle Scholar
  68. 68.
    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, drug related toxicitiy, and survival. J Clin Oncol. 2002;20:4040–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Smith TJ, Coyne PJ, Staats PS, Deer T, Stearns LJ, Rauck RL, et al. An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM). Ann Oncol. 2005;16:825–33. doi:10.1093/annonc/mdi156.PubMedCrossRefGoogle Scholar
  70. 70.
    Burton AW, Rajagopal A, Shah HN, Mendoza T, Cleeland C, Hassenbusch SJ, et al. Epidural and intrathecal analgesia is effective in treating refractory cancer pain. Pain Med. 2004;5:239–47. doi:10.1111/J.1526-4637.2004.04037.X.PubMedCrossRefGoogle Scholar
  71. 71.
    Ahmed SU, Martin NM, Chang Y. Patient selection and trial methods for intraspinal drug delivery for chronic pain: a national survey. Neuromodulation. 2005;8:112–20. doi:10.1111/j.1525-1403.2005.00227.x.PubMedCrossRefGoogle Scholar
  72. 72.
    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;6:142–52.PubMedCrossRefGoogle Scholar
  73. 73.
    Kim D, Saidov A, Mandhare V, Shuster A. Role of pretrial systemic opioid requirements, intrathecal trial dose, and nonpsychological factors as predictors of outcome for intrathecal pump therapy: one clinician's experience with lumbar postlaminectomy pain. Neuromodulation. 2011;14:165–75.Google Scholar
  74. 74.
    Kamran S, Wright BD. Complications of intrathecal drug delivery systems. Neuromodulation. 2001;4:111–5. doi:10.1046/j.1525-1403.2001.00111.x.PubMedCrossRefGoogle Scholar
  75. 75.
    Follett KA, Naumann CP. A prospective study of catheter-related complications of intrathecal drug delivery systems. J Pain Symptom Manage. 2000;19:209–15.PubMedCrossRefGoogle Scholar
  76. 76.
    Follett KA, Burchiel K, Deer T, Dupen S, Prager J, Turner MS, et al. Prevention of intrathecal drug delivery catheter-related complications. Neuromodulation. 2003;6:32–41. doi:10.1046/j.1525-1403.2003.03005.x.PubMedCrossRefGoogle Scholar
  77. 77.
    Deer TR, Prager J, Levy R, Burton A, Buchser E, Caraway D, et al. Polyanalgesic Consensus Conference–2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation. 2012;15:420–35. doi:10.1111/j.1525-1403.2012.00450.x. discussion 35.PubMedCrossRefGoogle Scholar
  78. 78.
    Peerdeman SM, de Groot V, Feller RE. In situ treatment of an infected intrathecal baclofen pump implant with gentamicin-impregnated collagen fleece. J Neurosurg. 2010;112:1308–10. doi:10.3171/2009.8.JNS081692.PubMedCrossRefGoogle Scholar
  79. 79.
    Diefenbeck M, Muckley T, Hofmann GO. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury. 2006;37 Suppl 2:S95–104. doi:10.1016/j.injury.2006.04.015.PubMedCrossRefGoogle Scholar
  80. 80.
    Ilias W, le Polain B, Buchser E, Demartini L; oPTIMa study group. Patient-controlled analgesia in chronic pain patients: experience with a new device designed to be used with implanted programmable pumps. Pain Pract. 2008;8:164–70.Google Scholar
  81. 81.
    Maeyaert J, Buchser E, Van Buyten JP, Rainov NG, Becker R. Patient-controlled analgesia in intrathecal therapy for chronic pain: safety and effective operation of the Model 8831 Personal Therapy Manager with a Pre-implanted SynchroMed Infusion System. Neuromodulation. 2003;6:133–41. doi:10.1046/j.1525-1403.2003.03021.x.PubMedCrossRefGoogle Scholar
  82. 82.
    Hayek SM. Intrathecal "microdosing": reality or artifact? Pain Med. 2012;13:1664–5. doi:10.1111/j.1526-4637.2012.01507.PubMedCrossRefGoogle Scholar
  83. 83.
    Brodner RA, Taub A. Chronic pain exacerbated by long-term narcotic use in patients with nonmalignant disease: clinical syndrome and treatment. Mt Sinai J Med. 1978;45:233–7.PubMedGoogle Scholar
  84. 84.
    Taylor CB, Zlutnick SI, Corley MJ, Flora J. The effects of detoxification, relaxation, and brief supportive therapy on chronic pain. Pain. 1980;8:319–29.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of AnesthesiologyCase Western Reserve UniversityClevelandUSA
  2. 2.Division of Pain MedicineUniversity Hospitals Case Medical CenterClevelandUSA

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