Advances in translational neuropathic research: example of enantioselective pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief in complex regional pain syndrome

Abstract

Historically, complex regional pain syndrome (CRPS) was poorly defined, which meant that scientists and clinicians faced much uncertainty in the study, diagnosis, and treatment of the syndrome. The problem could be attributed to a nonspecific diagnostic criteria, unknown pathophysiologic causes, and limited treatment options. The two forms of CRPS still are painful, debilitating disorders whose sufferers carry heavy emotional burdens. Current research has shown that CRPS I and CRPS II are distinctive processes, and the presence or absence of a partial nerve lesion distinguishes them apart. Ketamine has been the focus of various studies involving the treatment of CRPS; however, currently, there is incomplete data from evidence-based studies. The question as to why ketamine is effective in controlling the symptoms of a subset of patients with CRPS and not others remains to be answered. A possible explanation to this phenomenon is pharmacogenetic differences that may exist in different patient populations. This review summarizes important translational work recently published on the treatment of CRPS using ketamine.

Fig. 1

Structure of ketamine

Fig. 2

Patient with acute CRPS. The patient developed CRPS of the left hand after a radial fracture. Marked swelling appeared 2 weeks after the initial trauma. CRPS complex regional pain syndrome. (From Baron et al. [45], with permission)

Fig. 3

Plasma and urine concentrations of the major metabolites of (S)- and (R)-ketamine in a patient suffering from CRPS on day 3 of a 5-day continuous infusion. CRPS complex regional pain syndrome; DHNK dehydronorketamine; HK hydroxyketamine; HNK hydroxynorketamine; NK norketamine