Ketamine treatment for CRPS: new paper encouraging but not conclusive

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There continues to be significant interest concerning the use of Intravenous Ketamine Infusion as a treatment for chronic pain, particularly for Complex Regional Pain Syndrome (CRPS).

What is Ketamine?

Ketamine is an anaesthetic which in the past was often more associated with veterinary practice. As an NMDA receptor antagonist, it has a strong ability to block NMDA receptors in nerve cells. These receptors are very important for controlling ‘memory’ in nerve cells. To put that into context, chronic pain is often the result of trauma to nerve endings, which continue to send pain signals to the brain even when the original injury to the surrounding tissue has, to all intents and purposes, healed. It is thought that Ketamine helps to block these ‘wrong’ pain signals which are ‘memories’ of the now healed original injury.

Ketamine may additionally help to stimulate the growth of new nerve pathways. As the new nerve endings have no ‘memory’ of the original trauma, they send only normal, healthy signals to the brain. This process has been likened to rebooting a computer. Interestingly, researchers have found that Intravenous Ketamine Infusion can also be successful in treating therapy-resistant depression, which often goes hand-in-hand with chronic pain.

Meta-analysis

However, the use of Ketamine as a treatment for CRPS has remained controversial. Clinical trials to date have been relatively small scale and therefore less persuasive and this has certainly affected its availability as a treatment option. Now, the journal Current Pain and Headache Reports has published a paper, The Effect of Ketamine Infusion in the Treatment of Complex Regional Pain Syndrome: a Systemic Review and Meta-analysis.

A meta-analysis combines the results of a number of earlier studies to provide more data for statistical analysis and to help resolve discrepancies between those studies. They can also help to answer new questions not posed by those earlier studies.

In this case, 15 studies with a total of 258 participants with CRPS were included in the final analysis. The results of the analysis were summarised by the researchers as follows:

The current available studies regarding ketamine infusion for CRPS were reviewed, and meta-analyses were conducted to evaluate the efficacy of ketamine infusion in the treatment of CRPS. Our findings suggested that ketamine infusion can provide clinically effective pain relief in short term for less than 3 months. However, because of the high heterogeneity” [ie the diversity] “of the included studies and publication bias, additional random controlled trials and standardized multicenter studies are needed to confirm this conclusion. Furthermore, studies are needed to prove long-term efficacy of ketamine infusion in the treatment of CRPS.

Whilst far from conclusive, these results are at least encouraging and it is hoped that they may provide the impetus required for larger scale clinical trials.

Side effects

Like most drugs, Ketamine does have a number of side effects. In the short term, patients have reported headaches, nausea, night terrors and hallucinations. These symptoms tend to be relatively short lived.

However, more worryingly, excessive use of Ketamine can lead to serious, permanent damage to the bladder, known as Ketamine Bladder Syndrome or Ketamine Cystitis. This was first reported as recently as 2007 in the context of its illicit use as a recreational drug. Ketamine Bladder Syndrome occurs where damage to the lining of the bladder due to over use of Ketamine causes the bladder to shrink, resulting in serious and painful urological problems.

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