Introduction: Chronic neuropathic pain (NP) is an incapacitating illness caused by a lesion of the somatosensory nervous system and is associated with several diseases or syndromes. Since current treatment options lack adequate efficacy in the majority of patients, ketamine is often administered to treat refractory NP. Areas covered: This review gives an overview of new ketamine pharmacokinetic data including data on intranasal and inhaled ketamine. The outcome of seven systematic reviews and meta-analyses, published since 2012, on ketamine efficacy in NP is discussed. The reader will additionally get an understanding of ketamine's complex metabolism with emphasis on the metabolite hydroxynorketamine. Expert opinion: Proof of sustained, large effects of ketamine in the treatment of NP from randomized controlled clinical trials is lacking, although we cannot exclude selective ketamine efficacy in patients with central sensitization, opioid-induced hyperalgesia or opioid tolerance. Interestingly, data from observational trials and case series do suggest the efficacy of ketamine in producing effective pain relief in NP with positive patient-related outcome measures. Additional randomized trials in often illdefined groups of chronic pain patients are not useful and we suggest to conduct future studies in NP patients with central sensitization and/or with opioid refractory severe NP.

Number-based assessment tools are used to evaluate pain perception in patients and determine the effect of pain management. The aim of this study was to determine the ability of chronic and acute pain patients to score their response to randomly applied noxious stimuli and assess the effect of opioid treatment. Thirty-seven healthy controls, 30 fibromyalgia patients, and 62 postoperative patients with acute pain received random heat pain (Hp) and electrical pain (Ep) stimuli. All subjects rated their pain on an 11-point numerical rating scale (NRS). The data were analyzed using a penalty score system, based on the assumption that stimuli of higher intensity are scored with a greater NRS, and stratified into cohorts corresponding to "good," "mediocre," and "poor" scoring. Healthy controls were well able to score pain with 73% (Hp) and 81% (Ep) of subjects classified into cohort "good." Fibromyalgia had a negative effect on scoring with 45% (Hp, P = 0.03 vs controls) and 67% (Ep) of patients in cohort "good." In controls, scoring deteriorated during opioid administration leaving just 40% (Hp, P = 0.015 vs baseline) and 70% (Ep) of subjects in the cohort "good." Similar observations were made in fibromyalgia patients (P = 0.02) but not in surgical patients with postoperative pain. Consistency to grade pain using an NRS is high in healthy volunteers but deteriorates in chronic pain and during opioid administration to volunteers and chronic pain patients but not to acute pain patients.