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Antiglutamatergic Agents

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Central Pain Syndrome

Abstract

Antiglutamatergic agents, despite many initial hopes and several compounds tested, are not a mainstay of treatment of CP and are only infrequently used. The antiglutamatergic drug of choice remains parenteral ketamine. However, ketamine is a drug of addiction with neurotoxic (particularly with intrathecal/epidural administration) effects and unpleasant psychiatric side effects (e.g., somnolence, feelings of insobriety, nausea/vomiting, hallucinations, depersonalization/derealization, and drowsiness), most commonly in anxious and apprehensive individuals. On the other hand, acute administration of low dosages of ketamine has procognitive effects [1]. Renal damage and cystitis are known toxicities with repeated administrations. Rapid-acting routes of administration (e.g., intranasal) should be avoided and doses kept as low as possible. Ketamine (4 mg/kg PO = 0.4 mg/kg IM) can (rarely) induce hepatic failure; it has a low bioavailability (ca. 15%) and is rapidly metabolized to the much weaker norketamine. Long-term subcutaneous ketamine may lead to painful indurations. Ketamine is best reserved for parenteral in-hospital administration for urgent pain control and pharmacologic dissection. Recommended parenteral and oral dosages are from 0.05 to 0.5 mg/kg/h (intravenous or subcutaneous) and 0.2–0.5 mg/kg/dose PO two to three times daily with a maximum of 50 mg/dose three times daily, respectively. A study in a 51-strong mixed chronic pain group found that outpatient ketamine infusions significantly reduced VAS from 7 to 6.06 and improved sleep and enjoyment of life, but had no effect on general activity, mood, walking, work, and social interaction [2]. This is in line with controlled studies that do not find ketamine, however administered, particularly effective for CP. Nonetheless, some patients report pain abatement during IV challenge (Tables 12.1, 12.2, 12.3, 12.4, and 12.5).

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References

  1. Zhang MW, Ho RC. Controversies of the effect of ketamine on cognition. Front Psych. 2016;7:47.

    Google Scholar 

  2. Go R, Dwarki K, Chin M, Amdur R. Outcome measurements in chronic pain patients following ketamine infusions. Pain Med. 2015;16:563–4 (A112).

    Google Scholar 

  3. Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain. 1994;56(1):51–7. Erratum in: Pain 1994;58(3):433.

    Article  CAS  PubMed  Google Scholar 

  4. Eide PK, Stubhaug A, Stenehjem AE. Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation. Neurosurgery. 1995;37(6):1080–7.

    Article  CAS  PubMed  Google Scholar 

  5. Haines DR, Gaines SP. N of 1 randomised controlled trials of oral ketamine in patients with chronic pain. Pain. 1999;83(2):283–7.

    Article  CAS  PubMed  Google Scholar 

  6. Kvarnström A, Karlsten R, Quiding H, Gordh T. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol Scand. 2004;48(4):498–506.

    Article  PubMed  Google Scholar 

  7. Vranken JH, Dijkgraaf MG, Kruis MR, van Dasselaar NT, van der Vegt MH. Iontophoretic administration of S(+)-ketamine in patients with intractable central pain: a placebo-controlled trial. Pain. 2005;118(1–2):224–31.

    Article  CAS  PubMed  Google Scholar 

  8. Amr YM. Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician. 2010;13(3):245–9.

    PubMed  Google Scholar 

  9. McQuay HJ, Carroll D, Jadad AR, Glynn CJ, Jack T, Moore RA, Wiffeh PJ. Dextromethorphan for the treatment of neuropathic pain: a double-blind randomised controlled crossover trial with integral n-of-1 design. Pain. 1994;59(1):127–33.

    Article  CAS  PubMed  Google Scholar 

  10. Heiskanen T, Härtel B, Dahl ML, Seppälä T, Kalso E. Analgesic effects of dextromethorphan and morphine in patients with chronic pain. Pain. 2002;96(3):261–7.

    Article  CAS  PubMed  Google Scholar 

  11. Carlsson KC, Hoem NO, Moberg ER, Mathisen LC. Analgesic effect of dextromethorphan in neuropathic pain. Acta Anaesthesiol Scand. 2004;48(3):328–36.

    Article  CAS  PubMed  Google Scholar 

  12. Panitch HS, Thisted RA, Smith RA, Wynn DR, Wymer JP, Achiron A, Vollmer TL, Mandler RN, Dietrich DW, Fletcher M, Pope LE, Berg JE, Miller A, Psuedobulbar Affect in Multiple Sclerosis Study Group. Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol. 2006;59(5):780–7.

    Article  CAS  PubMed  Google Scholar 

  13. Wood T, Sloan R. Successful use of ketamine for central pain. Palliat Med. 1997;11(1):57.

    Article  CAS  PubMed  Google Scholar 

  14. Yamamoto T, Katayama Y, Hirayama T, Tsubokawa T. Pharmacological classification of central post-stroke pain: comparison with the results of chronic motor cortex stimulation therapy. Pain. 1997;72(1–2):5–12.

    Article  CAS  PubMed  Google Scholar 

  15. Canavero S, Bonicalzi V. The neurochemistry of central pain: evidence from clinical studies, hypothesis and therapeutic implications. Pain. 1998;74(2–3):109–14.

    Article  CAS  PubMed  Google Scholar 

  16. Enarson MC, Hays H, Woodroffe MA. Clinical experience with oral ketamine. J Pain Symptom Manag. 1999;17(5):384–6.

    Article  CAS  Google Scholar 

  17. Fisher K, Hagen NA. Analgesic effect of oral ketamine in chronic neuropathic pain of spinal origin: a case report. J Pain Symptom Manag. 1999;18(1):61–6.

    Article  CAS  Google Scholar 

  18. Vick PG, Lamer TJ. Treatment of central post-stroke pain with oral ketamine. Pain. 2001;92(1–2):311–3.

    Article  CAS  PubMed  Google Scholar 

  19. Sakai T, Tomiyasu S, Ono T, Yamada H, Sumikawa K. Multiple sclerosis with severe pain and allodynia alleviated by oral ketamine. Clin J Pain. 2004;20(5):375–6.

    Article  PubMed  Google Scholar 

  20. Cohen SP, DeJesus M. Ketamine patient-controlled analgesia for dysesthetic central pain. Spinal Cord. 2004;42(7):425–8.

    Article  CAS  PubMed  Google Scholar 

  21. Yamamoto T, Katayama Y, Obuchi T, Kano T, Kobayashi K, Oshima H, Fukaya C. Drug challenge test and drip infusion of ketamine for post-stroke pain. Pain Res. 2009;24:191–9.

    Article  Google Scholar 

  22. Hamauchi S, Kim K, Morimoto D, Isu T, Shimoda Y, Matsumoto R, Isobe M. Ketamine treatment for severe neuropathic pain with cervical spondylotic myelopathy. A case report. No Shinkei Geka. 2010;38(12):1121–5.

    PubMed  Google Scholar 

  23. Hussain AM, Khan MA. Pain management after traumatic spinal cord injury. J Coll Physicians Surg Pak. 2012;22(4):246–7.

    PubMed  Google Scholar 

  24. Kim K, Mishina M, Kokubo R, Nakajima T, Morimoto D, Isu T, Kobayashi S, Teramoto A. Ketamine for acute neuropathic pain in patients with spinal cord injury. J Clin Neurosci. 2013;20(6):804–7.

    Article  CAS  PubMed  Google Scholar 

  25. Cheng HW, Lam KO, Li CW, Chan KY, Sham MK. Successful analgesic use of ketamine infusion in malignant cord compression. Pain Med. 2015;16(10):2045–7.

    Article  PubMed  Google Scholar 

  26. Yamamoto T, Watanabe M, Obuchi T, Kano T, Kobayashi K, Oshima H, Fukaya C, Yoshino A. Importance of pharmacological evaluation in the treatment of poststroke pain by spinal cord stimulation. Neuromodulation. 2016;19(7):744–51.

    Article  PubMed  Google Scholar 

  27. Lo TC, Yeung ST, Lee S, Skavinski K, Liao S. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers-Danlos syndrome: a case report. J Pain Res. 2016;9:683–7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Takano M, Takano Y, Sato I. The effect of oral amantadine in chronic pain patients with positive ketamine challenge test. In: 9th world congress on pain, book of abstracts. Seattle: IASP Press; 1999. Abst. 220–P68.

    Google Scholar 

  29. Canavero S, Bonicalzi V, Paolotti R. Lack of effect of topiramate for central pain. Neurology. 2002;58(5):831–2.

    Article  CAS  PubMed  Google Scholar 

  30. Cohen SP, Abdi S. Venous malformations associated with central pain: report of a case. Anesth Analg. 2002;95(5):1358–60.

    Article  PubMed  Google Scholar 

  31. Bojak I, Day HC, Liley DT. Ketamine, propofol, and the EEG: a neural field analysis of HCN1-mediated interactions. Front Comput Neurosci. 2013;7:22.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Canavero S, Bonicalzi V, Castellano G. Two in one: the genesis of central pain. Pain. 1996;64(2):394–5.

    Article  CAS  PubMed  Google Scholar 

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Canavero, S., Bonicalzi, V. (2018). Antiglutamatergic Agents. In: Central Pain Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-56765-5_12

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  • DOI: https://doi.org/10.1007/978-3-319-56765-5_12

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