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.

Ketamine for Refractory Headache

“…Other factors might help predict response to ketamine, such as individual metabolism of the drug. 18 Metabolites of ketamine, including hydroxyketamine, dehydronorketamine, and other hydroxynorketamine molecules, may play a role in the treatment of depression, 19 and they could also be important in chronic pain conditions such as complex regional pain syndrome. 18 There is a subset of migraine and complex regional pain syndrome patients who have favorable response to ketamine, whereas others have minimal relief.…”

What is hydroxynorketamine and what can it bring to neurotherapeutics?

“…It should be noted that sub-anesthetic dosing of Ket has been used in the treatment of neuropathic pain such as Complex Regional Pain Syndrome, c.f. [11] and in pediatric sedation, c.f. [12].…”

Current challenges in translational pain research

“…Differences in pharmacokinetic and pharmacodynamic profiles between rodents and human beings are frequent challenges in the design and interpretation of clinical studies [22–24]. These include the half-life of a drug, as well as its bioavailability, elimination, dosing regimen, receptor affinity, and side effect profile.…”