Long-Term Antihyperalgesic and Opioid-Sparing Effects of 5-Day Ketamine and Morphine Infusion (“Burst Ketamine”) in Diabetic Neuropathic Rats

Abstract

This is the first preclinical study to use a model of neuropathic pain to demonstrate the utility of the BK procedure for delivering a long-lasting reduction in hyperalgesia and improved antinociceptive responsiveness to opioids.

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists

“… 19 – 23 Many experts consider the distinction between different pain types to be a continuum, rather than discrete classification categories. 18 Although the preponderance of preclinical evidence supporting an antinociceptive effect for ketamine has been conducted using peripheral neuropathic and central pain models, 24 – 26 there are a handful of studies demonstrating an analgesic benefit in inflammatory and other nonneuropathic animal models. 27 , 28 …”

“…In preclinical studies, ketamine has been shown to reduce opioid tolerance and hyperalgesia. 24 , 54 Although a recent meta-analysis demonstrated a small effect size for ketamine and other NMDA-receptor antagonists in reducing opioid consumption and improving analgesia in the perioperative setting, 55 the results of clinical studies have not been uniformly positive, which may in part be due to the multitude of factors that contribute to postsurgical pain and opioid consumption. 55 – 57 …”

The use of ketamine in a palliative-supportive care unit: a retrospective analysis

“…In conclusion, this retrospective study suggests that a burst of ketamine, associated with doses of m i d a z o l a m a b l e t o m a i n t a i n t h e c o n s c i o u s n e s s , may desensibilize states of hyperexcitation due to unfavourable opioid response, reversing tolerance and/ or hyperalgesia, facilitating and assisting the opioid switching. The role of ketamine is such complex and controversial that there is still incomplete evidence to state that ketamine is not of value in cancer pain (30,31). Strict protocols of a randomized controlled trial often do not reflect the difficult conditions of a selected population, that are challenging and hardly resolved by a level of evidence (24).…”

“…Strict protocols of a randomized controlled trial often do not reflect the difficult conditions of a selected population, that are challenging and hardly resolved by a level of evidence (24). In situations where analgesic options have failed, ketamine could be a reasonable "third line"choice (31)(32)(33). Large and multicenter studies should confirm these data, as controlled studies in the contest of a very selected and difficult population are unlikely to provide information to be applied in the clinical setting.…”

Ketamine — a unique adjuvant drug in pain treatment

“…The trial carried out on a model of diabetic neuropathy in animals showed that intravenous infusion of ketamine in a subanaesthetic dose for 5 days may reduce hyperalgesia and increase the response to opioids in the long term [17]. In an experimental model of human burn injuries, it was found that ketamine reduces the area of secondary hyperalgesia [18].…”