Jensen TS, et al. A new definition of neuropathic pain. Pain. 2011;152(10):2204–5.
Dworkin RH, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60(11):1524–34.
Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32.
Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991;44(3):293–9.
Swartjes M, et al. Ketamine does not produce relief of neuropathic pain in mice lacking the beta-common receptor (CD131). PLoS ONE. 2013;8(8):e71326.
Fallon MT. Neuropathic pain in cancer. Br J Anaesth. 2013;111(1):105–11.
Oshima E, et al. Continuous subcutaneous injection of ketamine for cancer pain. Can J Anaesth. 1990;37(3):385–6.
• Persson J. Ketamine in pain management. CNS Neurosci Ther. 2013;19(6):396–402. Fascinating narrative on the history and evolution of ketamine use in pain management.
•• Azari P, et al. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012;26(3):215–28. Provides comprehensive review of the efficacy and safety of ketamine specifically in the treatment of CRPS.
Fisher K, Coderre TJ, Hagen NA. Targeting the N-methyl-d-aspartate receptor for chronic pain management. Preclinical animal studies, recent clinical experience and future research directions. J Pain Symptom Manag. 2000;20(5):358–73.
Blonk MI, et al. Use of oral ketamine in chronic pain management: a review. Eur J Pain. 2010;14(5):466–72.
•• Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003;97(6):1730–9. Provides the first systematic literature review of the use of all forms of ketamine in various chronic pain etiologies including studies up to August 2002.
Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Med. 2012;13(2):263–9.
Quibell R, et al. Ketamine*. J Pain Symptom Manag. 2011;41(3):640–9.
Corssen G, Domino EF. Dissociative anesthesia: further pharmacologic studies and first clinical experience with the phencyclidine derivative CI-581. Anesth Analg. 1966;45(1):29–40.
Sinner B, Graf BM. Ketamine. Handb Exp Pharmacol. 2008;182:313–33.
Reich DL, Silvay G. Ketamine: an update on the first 25 years of clinical experience. Can J Anaesth. 1989;36(2):186–97.
•• Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60(7):341–8. Provides excellent review and analysis of use of low-dose ketamine. Identifies ketamine's primary role in the treatment of opioid resistant or central sensitisation pain with hyperalgesia or allodynia.
Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113(3):678–84.
Slikker W Jr, et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007;98(1):145–58.
Sadove MS, et al. Analgesic effects of ketamine administered in subdissociative doses. Anesth Analg. 1971;50(3):452–7.
Foster AC, Fagg GE. Neurobiology. Taking apart NMDA receptors. Nature. 1987;329(6138):395–6.
Lodge D, Anis NA, Burton NR. Effects of optical isomers of ketamine on excitation of cat and rat spinal neurones by amino acids and acetylcholine. Neurosci Lett. 1982;29(3):281–6.
Davies SN, Lodge D. Evidence for involvement of N-methylaspartate receptors in ‘wind-up’ of class 2 neurones in the dorsal horn of the rat. Brain Res. 1987;424(2):402–6.
Chizh BA. Low dose ketamine: a therapeutic and research tool to explore N-methyl-d-aspartate (NMDA) receptor-mediated plasticity in pain pathways. J Psychopharmacol. 2007;21(3):259–71.
Zukin SR, et al. Specific binding of [3H]phencyclidine in rat central nervous tissue: further characterization and technical considerations. Brain Res. 1983;258(2):277–84.
Lodge D, Johnson KM. Noncompetitive excitatory amino acid receptor antagonists. Trends Pharmacol Sci. 1990;11(2):81–6.
Zhou HY, Chen SR, Pan HL. Targeting N-methyl-d-aspartate receptors for treatment of neuropathic pain. Expert Rev Clin Pharmacol. 2011;4(3):379–88.
Salt TE, Wilson DG, Prasad SK. Antagonism of N-methylaspartate and synaptic responses of neurones in the rat ventrobasal thalamus by ketamine and MK-801. Br J Pharmacol. 1988;94(2):443–8.
Collins S, et al. NMDA receptor antagonists for the treatment of neuropathic pain. Pain Med. 2010;11(11):1726–42.
Eide PK, et al. Reply to ST Meller: Ketamine: relief from chronic pain through actions at the NMDA receptor. Pain. 1997;72(1–2):289–91.
Lindefors N, Barati S, O’Connor WT. Differential effects of single and repeated ketamine administration on dopamine, serotonin and GABA transmission in rat medial prefrontal cortex. Brain Res. 1997;759(2):205–12.
Mei XP, et al. Ketamine depresses toll-like receptor 3 signaling in spinal microglia in a rat model of neuropathic pain. Neurosignals. 2011;19(1):44–53.
Hayashi Y, et al. Microglial Ca(2+)-activated K(+) channels are possible molecular targets for the analgesic effects of S-ketamine on neuropathic pain. J Neurosci. 2011;31(48):17370–82.
Persson J. Wherefore ketamine? Curr Opin Anaesthesiol. 2010;23(4):455–60.
Ushida T, et al. Analgesic effects of ketamine ointment in patients with complex regional pain syndrome type 1. Reg Anesth Pain Med. 2002;27(5):524–8.
Kapur S, Seeman P. NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia. Mol Psychiatry. 2002;7(8):837–44.
Mathew SJ, et al. Ketamine for treatment-resistant unipolar depression: current evidence. CNS Drugs. 2012;26(3):189–204.
Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4.
Maeng S, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008;63(4):349–52.
Murrough JW, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134–42.
Zarate CA Jr, et al. A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856–64.
Mathews DC, Zarate CA Jr. Current status of ketamine and related compounds for depression. J Clin Psychiatry. 2013;74(5):516–7.
Tizabi Y, et al. Antidepressant-like effects of low ketamine dose is associated with increased hippocampal AMPA/NMDA receptor density ratio in female Wistar-Kyoto rats. Neuroscience. 2012;213:72–80.
Li N, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959–64.
Haile CN, et al. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int J Neuropsychopharmacol. 2014;17(2):331–6. doi:10.1017/S1461145713001119.
Mathisen LC, et al. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain. 1995;61(2):215–20.
Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-d-aspartate receptors. J Pharmacol Exp Ther. 1992;260(3):1209–13.
White PF, et al. Pharmacology of ketamine isomers in surgical patients. Anesthesiology. 1980;52(3):231–9.
Vranken JH, et al. Iontophoretic administration of S(+)-ketamine in patients with intractable central pain: a placebo-controlled trial. Pain. 2005;118(1–2):224–31.
Chong C, et al. Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009;29(5):317–24.
Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77(2):357–67. doi:10.1111/bcp.12094.
Haas DA, Harper DG. Ketamine: a review of its pharmacologic properties and use in ambulatory anesthesia. Anesth Prog. 1992;39(3):61–8.
Sigtermans MJ, et al. Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain. 2009;145(3):304–11.
Soto E, et al. Oral ketamine in the palliative care setting: a review of the literature and case report of a patient with neurofibromatosis type 1 and glomus tumor-associated complex regional pain syndrome. Am J Hosp Palliat Care. 2012;29(4):308–17.
Bell RF. Ketamine for chronic non-cancer pain. Pain. 2009;141(3):210–4.
Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2012;11:CD003351.
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.
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.
Kvarnstrom A, et al. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol Scand. 2004;48(4):498–506.
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.
Eide PK, et al. Relief of post-herpetic neuralgia with the N-methyl-d-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain. 1994;58(3):347–54.
Kim K, et al. Ketamine for acute neuropathic pain in patients with spinal cord injury. J Clin Neurosci. 2013;20(6):804–7.
Yamamoto T, et al. Pharmacological classification of central post-stroke pain: comparison with the results of chronic motor cortex stimulation therapy. Pain. 1997;72(1–2):5–12.
Backonja M, et al. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain. 1994;56(1):51–7.
Max MB, et al. Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo. Clin Neuropharmacol. 1995;18(4):360–8.
Felsby S, et al. NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride. Pain. 1996;64(2):283–91.
Leung A, et al. Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001;91(1–2):177–87.
Jorum E, Warncke T, Stubhaug A. Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-d-aspartate (NMDA) receptor antagonist ketamine–a double-blind, cross-over comparison with alfentanil and placebo. Pain. 2003;101(3):229–35.
Kvarnstrom A, et al. The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain. Acta Anaesthesiol Scand. 2003;47(7):868–77.
Lynch ME, et al. Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study. J Pain. 2005;6(10):644–9.
Huge V, et al. Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain. Eur J Pain. 2010;14(4):387–94.
Niesters M, et al. Influence of ketamine and morphine on descending pain modulation in chronic pain patients: a randomized placebo-controlled cross-over proof-of-concept study. Br J Anaesth. 2013;110(6):1010–6.
Gottrup H, et al. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain. Anesthesiology. 2006;104(3):527–36.
Mahoney JM, et al. Topical ketamine cream in the treatment of painful diabetic neuropathy: a randomized, placebo-controlled, double-blind initial study. J Am Podiatr Med Assoc. 2012;102(3):178–83.
Lynch ME, et al. Topical 2 % amitriptyline and 1 % ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2005;103(1):140–6.
Barros GA, et al. Topical (S)-ketamine for pain management of postherpetic neuralgia. An Bras Dermatol. 2012;87(3):504–5.
Eide PK, Stubhaug A. Relief of glossopharyngeal neuralgia by ketamine-induced N-methyl-aspartate receptor blockade. Neurosurgery. 1997;41(2):505–8.
Rabben T, Oye I. Interindividual differences in the analgesic response to ketamine in chronic orofacial pain. Eur J Pain. 2001;5(3):233–40.
Baad-Hansen L, et al. Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain. Pain. 2007;129(1–2):46–54.
Persson J, et al. The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans. Acta Anaesthesiol Scand. 1998;42(7):750–8.
Mitchell AC, Fallon MT. A single infusion of intravenous ketamine improves pain relief in patients with critical limb ischaemia: results of a double blind randomised controlled trial. Pain. 2002;97(3):275–81.
Nikolajsen L, et al. The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input. Pain. 1996;67(1):69–77.
Eichenberger U, et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesth Analg. 2008;106(4):1265–73.
Noppers I, et al. Absence of long-term analgesic effect from a short-term S-ketamine infusion on fibromyalgia pain: a randomized, prospective, double blind, active placebo-controlled trial. Eur J Pain. 2011;15(9):942–9.
Wurtman RJ. Fibromyalgia and the complex regional pain syndrome: similarities in pathophysiology and treatment. Metabolism. 2010;59(Suppl 1):S37–40.
Sorensen J, et al. Fibromyalgia–are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol. 1997;24(8):1615–21.
Graven-Nielsen T, et al. Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain. 2000;85(3):483–91.
Pickering AE, McCabe CS. Prolonged ketamine infusion as a therapy for complex regional pain syndrome: synergism with antagonism? Br J Clin Pharmacol. 2014;77(2):233–8. doi:10.1111/bcp.12157.
Price DD, et al. NMDA-receptor antagonists and opioid receptor interactions as related to analgesia and tolerance. J Pain Symptom Manag. 2000;19(1 Suppl):S7–11.
Schwartzman RJ, et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009;147(1–3):107–15.
Schilder JC, et al. Pain relief is associated with improvement in motor function in complex regional pain syndrome type 1: secondary analysis of a placebo-controlled study on the effects of ketamine. J Pain. 2013;14(11):1514–21. doi:10.1016/j.jpain.2013.07.013.
Dahan A, et al. Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain. Eur J Pain. 2011;15(3):258–67.
Correll GE, et al. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med. 2004;5(3):263–75.
Finch PM, Knudsen L, Drummond PD. Reduction of allodynia in patients with complex regional pain syndrome: a double-blind placebo-controlled trial of topical ketamine. Pain. 2009;146(1–2):18–25.
Du Mont J, et al. Drug-facilitated sexual assault in Ontario, Canada: toxicological and DNA findings. J Forensic Leg Med. 2010;17(6):333–8.
Albright JA, Stevens SA, Beussman DJ. Detecting ketamine in beverage residues: application in date rape detection. Drug Test Anal. 2012;4(5):337–41.
Kiefer RT, et al. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study. Pain Med. 2008;9(8):1173–201.
Kirkpatrick AF, Lubenow T. Regarding Bell and Moore, Intravenous ketamine for CRPS: making too much of too little? Pain 2010;150:10–11. Pain. 2010;151(2):556.
Schwartzman RJ, Alexander GM, Grothusen JR. The use of ketamine in complex regional pain syndrome: possible mechanisms. Expert Rev Neurother. 2011;11(5):719–34.
Olney JW, Labruyere J, Price MT. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science. 1989;244(4910):1360–2.
Olney JW. Excitotoxic amino acids and neuropsychiatric disorders. Annu Rev Pharmacol Toxicol. 1990;30:47–71.
Noppers IM, et al. Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: a report of 3 cases. Pain. 2011;152(9):2173–8.
Shahani R, et al. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007;69(5):810–2.
Chu PS, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int. 2008;102(11):1616–22.
Winstock AR, et al. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int. 2012;110(11):1762–6.
Mak SK, et al. Lower urinary tract changes in young adults using ketamine. J Urol. 2011;186(2):610–4.
Chen CH, et al. Ketamine-snorting associated cystitis. J Formos Med Assoc. 2011;110(12):787–91.
Niesters M, Dahan A. Pharmacokinetic and pharmacodynamic considerations for NMDA receptor antagonists in the treatment of chronic neuropathic pain. Expert Opin Drug Metab Toxicol. 2012;8(11):1409–17.
Miller LR, Cano A. Comorbid chronic pain and depression: who is at risk? J Pain. 2009;10(6):619–27.
Walker AK, et al. Neuroinflammation and comorbidity of pain and depression. Pharmacol Rev. 2014;66(1):80–101.
Haines DR, Gaines SP. N of 1 randomised controlled trials of oral ketamine in patients with chronic pain. Pain. 1999;83(2):283–7.
Furuhashi-Yonaha A, et al. Short- and long-term efficacy of oral ketamine in eight chronic-pain patients. Can J Anaesth. 2002;49(8):886–7.
Rabben T, Skjelbred P, Oye I. Prolonged analgesic effect of ketamine, an N-methyl-d-aspartate receptor inhibitor, in patients with chronic pain. J Pharmacol Exp Ther. 1999;289(2):1060–6.
Hardy J, et al. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. J Clin Oncol. 2012;30(29):3611–7.