Ketamine chronic pain

Gurney ME, Fleck TJ, Himes CS, Hall ED (1998) Riluzole preserves motor fimction in a transgenic model of familiar amyotrophic lateral sclerosis. Neurology 50 62-67 Haines DR, Gaines SP (1999) N of 1 randomised controlled trials oforal ketamine in patients with chronic pain. Pain 83 283-287... 

Davis, S. R. Ketamine in chronic pain a review, Aust. J. Hosp. Pharm. 1999, 28, 94-98. 

Oral ketamine is an effective analgesic in patients with chronic pain. In 21 patients with central and peripheral chronic neuropathic pain treated with oral ketamine, the starting dose was ketamine 100 mg/day, titrated upward by 40 mg/day increments every 2 days until a satisfactory effect was achieved, or until adverse effects became limiting (19). Nine patients discontinued ketamine because of intolerable adverse effects, including psychotomimetic symptoms, such as elevator effect or dissociative feelings, somnolence or insomnia, and sensory changes such as taste disturbance and somatic sensations. 

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

Stotz M, Oehen HP, Gerber H. Histological findings after long-term infusion of intrathecal ketamine for chronic pain a case report. J Pain Symptom Manage 1999 18(3) 223-8. 

The animal data are supported by some clinical observations with medicines that are known to block NMDA receptor activation, even if they have other pharmacological activities. Thus, low-dose ketamine reduced chronic pain associated with spinal cord injury (Hide et al., 1995) and could reduce pain in patients with peripheral nerve injury and with peripheral vascular disease (Felsby et al., 1996 Eisenberg and Pud, 1998). Amantadine could significantly reduce pain in cancer patients and in those with trauma-induced neuropathic pain (Pud et al., 1998). Although it is not possible to identify that the analgesic action of amantadine and ketamine in chronic pain states is through an action on the NMDA receptor, the clinical data do support the hypothesis that the animal data have gener-... 

Blonk MI, Koder BG, van den Bemt PMLA, Huygen FJPM. Use of oral ketamine in chronic pain management a review. Eur J Pain 2010 14 466-72. 

Severe chronic pain is sometimes treated with co-administered ketamine/ bupivacaine. These compounds were isolated from plasma and analyzed on a cyanopropyl column (A = 215nm). A 718/220/80/2 water (lOmM NaH2p04 buffer at pH 2.34)/methanol/acetonitrile/H3P04 mobile phase generated baseline separation in <8 min. The peaks were quite tailed. Introduction of TEA and/or a TFA/triethylamine buffer syston in place of the phosphate system may remedy this. Calibration curves from 10 to 400ng/mL (ketamine) and 125 to 4000ng/mL (bupivacaine) were stated, with the lowest concentration serving as the quantitation limit. Detection limits (S/N = 4) of 1 ng injected and 0.8 ng injected, respectively, were reported [563]. 

Hocking G, Cousins MJ. Ketamine in chronic pain management an evidence-based review. Anesth Analg 2003 97 1730-1739. 

Sigtermans M, et al. An observational study on the effect of S(-i-)-ketamine on chronic pain versus experimental acute pain in Complex Regional Pain Syndrome type 1 patients. Eur J Pain 2009 ... 

There are some limited data showing the use of ketamine in the treatment of chronic pain. Ketamine 317... 

Substantial published literature ranging from cases and case series through meta-analyses of randomized controlled trials describes the parenteral administration of subanesthetic doses of ketamine to provide analgesia in patients with acute pain such as burn pain, chronic pain such as neuropathic pain, and cancer-related pain as both a stand-alone analgesic as well as an adjuvant to opioids [5]. 

In summary, subanesthetic doses of ketamine are now used increasingly in anesthesia practice as part of multimodal regimens for acute pain, as well as add-on therapy in selected patients with chronic pain. Our intranasal ketamine product candidate provides a simple, non-invasive alternative to the present invasive (IM, IV) methods of systemic administration of low-dose ketamine, and has the potential to make this agent available on a broader scale. However, it is still under development and the final assessment of its benefits and risks will await completion and integration of the results of its entire clinical investigative program. 

Carr DB, Goudas LC, Denman WT, et al. Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain a randomized, double-blind, placebo-controlled, crossover study. Pain 2004 108 17-27. 

Ketamine has been investigated in the prevention of chronic pain after thoracotomy in 86 patients who were randomized to ketamine or placebo after a standardized general anesthetic using propofol or etomi-date [36 ]. The treatment group received... 

Dual6 C, Sibaud F, Guastella V, Vallet L, Gimbert YA, Taheri H, Filaire M, Schoeffler P, Dubray C. Perioperative ketamine does not prevent chronic pain after thoracotomy. Eur J Pain 2009 13(5) 497-505. 

A further case series has described the use of sub-anaesthetic doses of ketamine (emergency department for indications such as procedural sedation, patient with chronic pain on opioids requiring breakthrough pain and pain causing emotional distress [42 ]. The author describes three cases ... 

Niesters M, Aarts L, Sarton E, Dahan A. Influence of ketamine and morphine on descending pain modulation in chronic pain patients a randomized placebo-controUed cross-over proof-of-concept study. Br J Anaesth 2013 110 1010-6. 

BredlauAL,McDermottMP, Adams HR, Dworkin RH, Venuto C, Fisher SG, et al. Oral ketamine for children with chronic pain a pilot phase... 

Felsby S, Nielsen J, Arendtnielsen L, Jensen TS (1996) NMDA receptor blockade in chronic neuropathic pain a comparison of ketamine and magnesium chloride. Pain 64 283-291 Ferraguti F, Baldani-Guerra B, Corsi M, Nakanishi S, Corti C (1999) Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors. Eur J Neurosci 11 2073-2082... 

Pellegrini-Giampietro DE, Bennett MVL, Zukin RS (1992) Are Ca-2-i--permeable kainate/ AMPA receptors more abundant in immature brain. Neurosci Lett 144 65-69 Persson J, Hasselstrom J, Wiklund B, et al (1998) The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans. Acta Anaesthesiol Scand 42 750-758... 

Neurotoxicity due to focal lymphocytic vasculitis has been reported close to the catheter injection site in a patient who received intrathecal ketamine infusion for chronic cancer pain (21). 

Our intranasal ketamine product candidate is being developed for the management of acute moderate to severe pain, as well as BTP in patients on chronic opioid therapy. Pilot studies in both of these pain models, using the exploratory formulation of Ereska, have yielded encouraging results for safety and efficacy. A randomized, double-blind, singledose parallel study [3] tested 10, 30 and 50 mg IN... 

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