Background: Malignant hyperthermia (MH) is a rare but life-threatening disease that occurs during general anesthesia. The actual prevalence of MH remains unclear, and the association between MH and various anesthetic drugs remains controversial because of a lack of universal reporting. Methods: Using the Japanese Diagnosis Procedure Combination database, we collected data of inpatients who had general anesthesia between July and December 2006-2008. Patients' age, gender, diagnoses, procedures, and the use of drugs during anesthesia, including volatile agents, muscle relaxants, and propofol, were investigated. Univariate comparisons were made to examine the relationship of each anesthetic drug or demographic factor with the occurrence of MH. Results: Of 1,238,171 surgical patients undergoing general anesthesia, we identified 17 MH patients. Only one in-hospital death was identified. Men were significantly more likely to contract MH(odds ratio: 3.49; 95% CI 1.14 -10.7; P=0.029). No MH patient was found among 19,871 suxamethonium users. The prevalence of MH was relatively high in users of sevoflurane and rocuronium compared with nonusers but was not statistically significant [corrected].. Conclusions: No single drug was significantly associated with the occurrence of MH. Data should be continuously compiled, and further analyses with larger numbers of cases are necessary to identify possible causative agents.

Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Understanding the concept, disease entity, and burden of neuropathic pain, as well as its screening and diagnosis are important steps before starting pharmacotherapy. As well as other guidelines, the guidelines propose several lines of pharmacotherapies in a step-wise manner. To name a few different points, our guidelines propose an extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus, which has been found to be effective for post-herpetic neuralgia in Japan, as one of the second-line drugs. When prescribing opioid analgesics, proposed as the third-line drugs, for neuropathic pain, the guidelines recommend physicians continue evaluations on either abuse or addiction. The guidelines do not recommend concomitant use of nonsteroidal anti-inflammatory drugs and acetaminophen because of lack of clinical evidence of their efficacy. If patients do not respond well to pharmacotherapy, which is prescribed in a step-wise manner, other treatment strategies should be considered to improve patients’ activities of daily living and QOL.

Objectives. Overweight negatively affects musculoskeletal health; hence obesity is considered a risk factor for osteoarthritis and chronic low back pain. This was conducted to determine if obesity affects neuropathic pain, usually considered unrelated to the weight-load on the musculoskeletal system.Methods. Using a cut-off body mass index value of 25, 44 patients with neuropathic pain were grouped into a “high-BMI” group and a “normal-BMI” group.Results. The numeric rating scale of the high-BMI group was significantly higher than that of the normal-weight group (P<0.05). The total NPSI scores were significantly higher (P<0.01), and the paroxysmal pain and the negative symptoms were more serious in the high-BMI group than in the normal-BMI group. The high-BMI subjects also had significantly higher SF-MPQ scores (P<0.05). However, both physical and mental health status on the SF-36 were comparable between the groups.Discussion. Neuropathic pain that did not arise from musculoskeletal damage was higher in the high-BMI patients. Paroxysmal pain was more severe, suggesting that neural damage might be aggravated by obesity-associated inflammation. These findings should have needed to be confirmed in future studies.

The underlying mechanisms of neuropathic pain remain to be elucidated. Basic animal research has suggested that lysophosphatidic acids, which are bioactive lipids produced by autotaxin from lysophosphatidylcholine, may play key roles in the initiation and maintenance of neuropathic pain. Here, we investigated the clinical relevance of lysophosphatidic acids signaling on neuropathic pain in humans. Eighteen patients who had been diagnosed with neuropathic pain with varied etiologies participated in the study. Cerebrospinal fluid samples were obtained by lumbar puncture and the concentrations of 12 species of lysophosphatidic acids and lysophosphatidylcholine, autotaxin, and the phosphorylated neurofilament heavy subunit were measured. Pain symptoms were assessed using an 11-point numeric rating scale and the Neuropathic Pain Symptom Inventory regarding intensity and descriptive dimensions of neuropathic pain. The total lysophosphatidic acids were significantly associated with both pain intensity and symptoms. 18:1 and 20:4 lysophosphatidic acids in particular demonstrated the most correlations with dimensions of pain symptoms. Autotaxin and the phosphorylated neurofilament heavy subunit showed no association with pain symptoms. In conclusions, lysophosphatidic acids were significantly associated with pain symptoms in neuropathic pain patients. These results suggest that lysophosphatidic acids signaling might be a potential therapeutic target for neuropathic pain.

Complex regional pain syndrome (CRPS) is a syndrome that describes a broad spectrum of sensory, motor and autonomic-like features with unproven etiology. The International Association for the Study of Pain (IASP) diagnostic criteria of CRPS shows high sensitivity but poor specificity. Using statistical-pattern-recognition methods, American researchers have suggested a new set of criteria offering acceptable sensitivity and high specificity. However, non-American CRPS patients present distinct subsets of CRPS-related signs/symptoms from those of American patients. Here, we followed a series of American studies to develop a set of CRPS diagnostic criteria that would be most suitable for the Japanese population. A standardized sign/symptom checklist was used in patient evaluations to obtain data on CRPS-related signs/symptoms in 195 participants meeting the IASP criteria. Using factor analysis, we grouped CRPS-related signs/symptoms into five distinct subgroups (trophic change, motor dysfunction, abnormal pain processing, asymmetric sudomotor activity and asymmetric edema). Discriminant function analysis of these subgroups, regarding their ability to discriminate between CRPS and non-CRPS etiology, indicated that modifying the IASP criteria could increase clinical diagnostic accuracy in the Japanese population. Our diagnostic criteria are not exactly the same as the American criteria, indicating a need for more regionally based CRPS diagnostic criteria. Different sets of CRPS diagnostic criteria could lead to dissimilar patients being diagnosed as CRPS, however, presenting problems for translation of therapeutic effects found in various studies. Therefore, we further recognize a need for a global set of common CRPS diagnostic criteria.

Delirium is the most common postoperative complication of the central nervous system (CNS) that can trigger long-term cognitive impairment. Its underlying mechanism is not fully understood, but the dysfunction of the blood-brain barrier (BBB) has been implicated. The serum levels of the axonal damage biomarker, phosphorylated neurofilament heavy subunit (pNF-H) increase in moderate to severe delirium patients, indicating that postoperative delirium can induce irreversible CNS damage. Here, we investigated the relationship among postoperative delirium, CNS damage and BBB dysfunction, using pNF-H as reference. Blood samples were collected from 117 patients within 3 postoperative days. These patients were clinically diagnosed with postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit. We measured intercellular adhesion molecule-1, platelet and endothelial cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin as biomarkers for BBB disruption, pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6), and pNF-H. We conducted logistic regression analysis including all participants to identify independent biomarkers contributing to serum pNF-H detection. Next, by multiple regression analysis with a stepwise method we sought to determine which biomarkers influence serum pNF-H levels, in pNF-H positive patients. Of the 117 subjects, 41 were clinically diagnosed with postoperative delirium, and 30 were positive for serum pNF-H. Sensitivity and specificity of serum pNF-H detection in the patients with postoperative delirium were 56% and 90%, respectively. P-selectin was the only independent variable to associate with pNF-H detection (P < 0.0001) in all 117 patients. In pNF-H positive patients, only PECAM-1 was associated with serum pNF-H levels (P = 0.02). Serum pNF-H could be an objective delirium biomarker, superior to conventional tools in clinical settings. In reference to pNF-H, P-selectin may be involved in the development of delirium-related CNS damage and PECAM-1 may contribute to the progression of delirium- related CNS damage.