Levels of preoperative cerebrospinal fluid pro-inflammatory mediators and chronic pain after total knee arthroplasty surgery.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered. Here, we examined the associations between preoperative neuroinflammatory states and pre- and postsurgical chronic pain in TKA surgery. METHODS: The data of 42 patients undergoing elective TKA surgery for chronic knee arthralgia at our hospital were analyzed in this prospective study. Patients completed the following questionnaires: brief pain inventory (BPI), hospital anxiety and depression scale, painDETECT, and pain catastrophizing scale (PCS). Cerebrospinal fluid (CSF) samples were collected preoperatively and concentrations of IL-6, IL-8, TNF, fractalkine, and CSF-1 were measured by electrochemiluminescence multiplex immunoassay. CPSP severity was ascertained, using the BPI, 6 months postsurgery. RESULTS: While no significant correlation was observed between the preoperative CSF mediator levels and preoperative pain profiles, the preoperative fractalkine level in the CSF showed a significant correlation with CPSP severity (Spearman's rho = -0.525; p = .002). Furthermore, multivariate linear regression analysis revealed that the preoperative PCS score (standardized ß coefficient [ß]: .11; 95% confidence interval [CI]: 0.06-0.16; p < .001) and CSF fractalkine level (ß: -.62; 95% CI: -1.10 to -0.15; p = .012) were independent predictors of CPSP severity 6 months after TKA surgery. CONCLUSIONS: We identified the CSF fractalkine level as a potential predictor for CPSP severity following TKA surgery. In addition, our study provided novel insights into the potential role of neuroinflammatory mediators in the pathogenesis of CPSP.

Effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles of diabetic and non-diabetic patients with low back pain.

PURPOSE: We aimed to investigate the effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles and pituitary-adrenal axis functions of diabetic and non-diabetic patients with low back pain. METHODS: A total of 28 patients (ten diabetic [DM group] and 18 non-diabetic patients [non-DM group]) with low back pain were followed-up. Transforaminal epidural low-dose dexamethasone (1.65 mg) injections were repeated every 7-14 days for 8 weeks. Fasting blood sugar (FBS), hemoglobin A1c (HbA1c), morning plasma adrenocorticotropin (ACTH), and cortisol levels were measured at baseline and during the 8-week follow-up period. RESULTS: There were no significant changes in FBS and HbA1c levels between baseline and 8-week follow-up period in both DM and non-DM groups (difference in FBS [95% confidence Interval, CI]: - 0.6 mg/dL [- 6.4, 5.1], p = 0.83 in the non-DM group, - 0.2 mg/dL [- 26.2, 25.8], p = 0.99 in the DM group; difference in HbA1c [95% CI] - 0.02% [- 0.1, 0.1], p = 0.69 in the non-DM group, 0.04% [- 0.3, 0.4], p = 0.79 in the DM group). There were no significant longitudinal changes in ACTH and cortisol levels (ACTH, p = 0.38 [baseline vs. 8 week], p = 0.58 [non-DM vs. DM]; cortisol, p = 0.52 [baseline vs. 8 week], p = 0.90 [non-DM vs. DM]). CONCLUSIONS: Repeated transforaminal epidural low-dose dexamethasone injections provided no significant elevations in blood glucose or suppression of the pituitary-adrenal axis for two months from the first injection in both diabetic and non-diabetic patients. Our results indicate the intermediate-term safety of repeated transforaminal epidural low-dose dexamethasone injections with regard to the effect on glucose profile and pituitary-adrenal axis functions.

Interaction between anesthetic conditioning and ischemic preconditioning on metabolic function after hepatic ischemia-reperfusion in rabbits.

BACKGROUND: Both anesthetic-induced and ischemic preconditioning are protective against hepatic ischemia-reperfusion injury. However, the effects of these preventive methods on the metabolic function remain to be elucidated. We investigated the anesthetic conditioning and ischemic preconditioning on the metabolic function of the rabbit model of hepatic ischemia-reperfusion. METHODS: After approval by the institutional animal care and use committee, 36 Japanese White rabbits underwent partial hepatic ischemia for 90 min either under sevoflurane or propofol anesthesia. All the rabbits underwent 90 min of hepatic ischemia, and half of the rabbits in each group underwent additional 10-min ischemia and 10-min reperfusion before index ischemia. Hepatic microvascular blood flow was intermittently measured during reperfusion period, and galactose clearance, serum aminotransferase activities, and lactate concentrations were determined 180 min after reperfusion. RESULTS: Neither anesthetic conditioning with sevoflurane nor ischemic preconditioning altered hepatic microvascular blood flow during reperfusion and serum transaminase activities after reperfusion. However, galactose clearance of reperfused liver was significantly higher under sevoflurane anesthesia than propofol (0.016 ± 0.005/min vs. 0.011 ± 0.004/min). Statistically significant interaction between anesthetic choice and application of ischemic preconditioning suggests that the ischemic preconditioning is selectively protective under propofol anesthesia. Increase of blood lactate concentration was significantly suppressed under sevoflurane anesthesia compared to propofol (1.5 ± 0.8 vs. 3.9 ± 1.4 mmol/l) without any statistically significant interaction with the application of ischemic preconditioning. CONCLUSION: Sevoflurane attenuated the decrease of galactose clearance and increase of the blood lactate after reperfusion compared to propofol. Application of ischemic preconditioning was significantly protective under propofol anesthesia.

Fear-avoidance beliefs are independently associated with the prevalence of chronic pain in Japanese workers.

PURPOSE: Pain is a global public health problem with implications for both personal and social heath. Fear-avoidance beliefs (FABs) have been demonstrated to negatively impact and prolong pain in many Western countries, but little is known about the association between FABs and chronic pain (CP) in Asian countries, including Japan. We examined the relationship between FABs and CP in Japanese white-collar workers, a growing population with a high prevalence of CP. METHODS: Questionnaires and company records were used to gather data from 433 Japanese white-collar workers. Data were related to experience of pain, participant sociodemographic/health/lifestyle characteristics, fear-avoidance beliefs [Tampa Scale for Kinesiophobia (TSK)], work-related psychosocial factors (Brief Job Stress Questionnaire), and depressive illness [Psychological Distress Scale (K6)]. Analysis of covariance and multilevel logistic regression modeling were used to analyze associations between the data while controlling for factors known to influence CP prevalence. RESULTS: Prevalence rate of CP was 11.1% (48 of 433 persons). Adjusted odds ratios for participants with CP significantly increased in participants with high TSK scores, even after adjusting for factors known to influence CP prevalence. CONCLUSION: We found a significant association between high TSK scores and CP in Japanese white-collar workers when controlling for other known factors that influence CP such as work-related psychosocial characteristics and depressive conditions. This finding suggests that FABs are independently associated with prevalence of CP.

Deep anesthesia worsens outcome of rats with inflammatory responses.

OBJECTIVE: We tested the hypothesis that deep anesthesia with sevoflurane, known as a potent immunomodulator, for 4 h would worsen the 24-h outcomes of rats through modulation of the inflammatory responses. METHODS: Forty-nine male Wistar rats, administered low dose of lipopolysaccharide (0.5 mg/kg) intravenously to elicit moderate inflammatory responses mimicked mild surgical stress, underwent one minimum alveolar concentration (MAC) or 2 MAC sevoflurane anesthesia for 4 h. The 24-h survival rate, arterial blood gases, plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations, and rate of T lymphocyte apoptosis in spleen were evaluated. We further examined the effects of hypotension and TNF-α discharge on the survival rate. RESULTS: The survival rate in 2 MAC group was significantly lower accompanied with decreased base excess and increased level of cytokines (IL-6, TNF-α) compared to 1 MAC group. The apoptosis rate did not differ between the two groups. Neither norepinephrine infusion to restore hypotension nor administration of anti-TNF-α antibody improved the outcome in the 2 MAC group. CONCLUSIONS: Deep anesthesia with sevoflurane even for a short-term period augments the release of inflammatory cytokines evoked by inflammatory insults like surgical stress, impairs the acid-base balance, and subsequently deteriorates the outcomes.

Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice.

BACKGROUND AND AIM: Because neutrophil gelatinase-associated lipocalin (NGAL) is known to provide significant bacteriostatic effects during infectious conditions, we tested the hypothesis that this protein is up-regulated and secreted into the intraluminal cavity of the gut under critically ill conditions and is thus responsible for the regulation of bacterial overgrowth. METHODS: With our institutional approval, male C57BL/6J mouse (6-7 weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with naïve control. We assessed NGAL protein concentrations in intestinal lumen and up-regulation of NGAL expression in intestinal tissues in in vivo as well as ex vivo settings. Simultaneously, we examined the effects of NGAL protein administration on the growth of Escherichia coli (E. coli) in in vivo and in vitro experimental settings. The localization of NGAL in intestinal tissues and lumen was also assessed by immunohistological approach using NGAL antibody. RESULTS: Both lipopolysaccharide and peritonitis insults evoked the marked up-regulation of NGAL mRNA and protein levels in gut tissues such as crypt cells. In addition, the administration of NGAL protein significantly inhibited the outgrowth of enteric E. coli under both in vitro and in vivo conditions, accompanied by histological evidence. CONCLUSION: Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.

The effects of epidural anesthesia on growth of Escherichia coli at pseudosurgical site: the roles of the lipocalin-2 pathway.

BACKGROUND: Neutrophil-derived lipocalin-2 exerts bacteriostatic effects through retardation of iron uptake by the Gram-negative organisms like Escherichia coli. We tested the hypothesis that the expression of lipocalin-2, a bacteriostatic protein, was upregulated by induction of surgical site infection (SSI) with E coli in healthy and diseased rats and that epidural anesthesia modulated its expression. METHODS: Male Wistar rats were randomized into a healthy or disease group, the latter of which was administered lipopolysaccharide. Both groups were further divided into 3 subgroups, the control, saline, and lidocaine groups: group healthy control (n = 10), healthy saline (n = 10), and healthy lidocaine (n = 10) versus group disease control (n = 15), disease saline (n = 18), and disease lidocaine (n = 19), respectively. While saline was epidurally administered to the control and saline groups, lidocaine was administered to the lidocaine groups. Except for the control groups, E coli was injected to the pseudosurgical site to mimic SSI after abdominal surgery. Plasma concentrations of inflammatory cytokine and lipocalin-2 were measured. At 72 hours, the surgical site tissues were obtained to evaluate mRNA expression of lipocalin-2 and E coli DNA expression. RESULTS: All disease subgroups showed markedly increased plasma inflammatory cytokines versus the healthy subgroups. Among the disease subgroups, plasma concentrations of lipocalin-2 and tissue mRNA expression of lipocalin-2 were significantly increased in group disease lidocaine versus the others. Concurrently, E coli DNA expression in the tissue specimens was also significantly lower in group disease lidocaine as compared with group disease saline. CONCLUSIONS: Epidural anesthesia was associated with an increase in the expression lipocalin-2 and a decrease in the expression of E coli DNA at pseudosurgical sites in sick but not healthy rats. These observations suggest a potential mechanism by which epidural anesthesia could reduce the risk of SSI.

Long-term outcomes of percutaneous radiofrequency thermocoagulation of gasserian ganglion for 2nd- and multiple-division trigeminal neuralgia.

OBJECTIVES: The objective of this study was to examine the long-term outcome of percutaneous radiofrequency thermocoagulation (PRT) of the Gasserian ganglion for the 2nd division and multiple division trigeminal neuralgia (TN), compared to the isolated 3rd division TN. METHODS: One hundred and forty-eight procedures performed in 89 patients with typical TN between April 2004 and September 2011 in a single pain center were retrospectively analyzed. Baseline characteristics of these patients, immediate outcome, duration pain-free, and complications were obtained from their medical records and questionnaires sent in June 2012. Duration pain-free was assessed by Kaplan-Meier analysis. RESULTS: Of the 148 PRT of the Gasserian ganglion, 37 procedures were performed for isolated 2nd-division TN (V2 TN), 67 procedures were for both 2nd- and 3rd-division TN (V2 + V3 TN), and 38 procedures were for isolated 3rd-division TN (V3 TN). The remaining 6 procedures were performed for V1 + V2 TN and V1 + V2 + V3 TN. Immediate success rates of PRT for V2 TN, V2 + V3 TN, and V3 TN were 100%, 86.6%, and 100%, respectively, whereas the durations pain-free for V2 TN and V2 + V3 TN were significantly shorter than that for V3 TN (9, 12, and 36 months, respectively: P = 0.012). CONCLUSION: For 2nd-division TN and multiple-division TN, less long-term pain relief after PRT of the Gasserian ganglion can be expected compared with that for isolated trigeminal 3rd-division neuralgia, even if immediate pain relief is achieved.

A novel hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonist prevents ischemic neuronal death.

Physiological levels of H(2)S exert neuroprotective effects, whereas high concentrations of H(2)S may cause neurotoxicity in part via activation of NMDAR. To characterize the neuroprotective effects of combination of exogenous H(2)S and NMDAR antagonism, we synthesized a novel H(2)S-releasing NMDAR antagonist N-((1r,3R,5S,7r)-3,5-dimethyladamantan-1-yl)-4-(3-thioxo-3H-1,2-dithiol-4-yl)-benzamide (S-memantine) and examined its effects in vitro and in vivo. S-memantine was synthesized by chemically combining a slow releasing H(2)S donor 4-(3-thioxo-3H-1,2-dithiol-4-yl)-benzoic acid (ACS48) with a NMDAR antagonist memantine. S-memantine increased intracellular sulfide levels in human neuroblastoma cells (SH-SY5Y) 10-fold as high as that was achieved by ACS48. Incubation with S-memantine after reoxygenation following oxygen and glucose deprivation (OGD) protected SH-SY5Y cells and murine primary cortical neurons more markedly than did ACS48 or memantine. Glutamate-induced intracellular calcium accumulation in primary cortical neurons were aggravated by sodium sulfide (Na(2)S) or ACS48, but suppressed by memantine and S-memantine. S-memantine prevented glutamate-induced glutathione depletion in SH-SY5Y cells more markedly than did Na(2)S or ACS48. Administration of S-memantine after global cerebral ischemia and reperfusion more robustly decreased cerebral infarct volume and improved survival and neurological function of mice than did ACS48 or memantine. These results suggest that an H(2)S-releasing NMDAR antagonist derivative S-memantine prevents ischemic neuronal death, providing a novel therapeutic strategy for ischemic brain injury.

Decreased Interoceptive Awareness as a Risk Factor for Moderate to Severe Pain in Japanese Full-Time Workers: A Longitudinal Cohort Study.

Interoceptive awareness, the conscious perception of internal bodily states, is a key construct of mind-body interaction. Decreases in interoceptive awareness, as measured by the Multidimensional Assessment of Interoceptive Awareness (MAIA), are found in chronic pain patients. In this study, we explored whether a specific aspect of interoceptive awareness is a risk for the onset and chronicity of pain. A longitudinal cohort study was conducted in 2018 and 2020 among a sample of full-time workers in an industrial manufacturing company in Japan. Participants completed a questionnaire on pain intensity, MAIA, exercise habits, kinesiophobia, psychological distress and work stress. Principal component analyses using the MAIA identified two principal components: self-control and emotional stability. Low emotional stability was associated with the prevalence of moderate to severe pain in 2020 among people with mild or no pain in 2018 (p < 0.01). Lack of exercise habits were associated with the prevalence of moderate to severe pain in 2020 among people with pain in 2018 (p < 0.01). Furthermore, exercise habits were associated with reduction in kinesiophobia among people with moderate to severe pain in 2018 (p = 0.047). Overall, these findings indicate that low emotional stability may be a risk for the onset of moderate to severe pain; lack of exercise habits may sustain kinesiophobia and be a risk for the chronicity of pain.

Impact of continued mindfulness practice on resilience and well-being in mindfulness-based intervention graduates during the COVID-19 pandemic: A cross-sectional study.

Aim: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented stress. Mindfulness-based interventions (MBIs) are known to be effective in reducing stress. However, it is unclear how long-term outcomes differ between those who continue mindfulness practice after MBIs and those who do not. In this study, we hypothesized that those who continued mindfulness practice would have higher stress tolerance, and we examined this hypothesis through a survey of MBI graduates. In this study, we examined the association between the continuation of mindfulness practice among MBI completers and individual stress during the COVID-19 epidemic. Methods: A cross-sectional survey of MBI graduates was conducted. The physical and mental health states were compared between those who established a habit of mindfulness practice (practice group) and those who did not (no practice group). Results: The data were collected from 95 participants (response rate: 53.7%). Of the total respondents, 66 (69.5%) practiced mindfulness. Although the degree of perceived stress due to the COVID-19 pandemic was not statistically different between the practice and no practice groups, the practice group showed significantly lower levels of depression (p = 0.007), higher levels of resilience (p = 0.006), higher levels of overall health (p = 0.006), and higher levels of mental health (p = 0.039). The effect of mindfulness practice on reducing depression was fully mediated by resilience. Conclusion: Among MBI graduates, those who regularly practiced mindfulness had lower levels of depression and higher levels of physical and mental health. Thus, the continuation of mindfulness practice increases resilience, buffers against new stressors such as the COVID-19 pandemic, and has the potential to prevent depression.

Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice.

BACKGROUND: Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia/reperfusion injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR). METHODS AND RESULTS: Adult male mice were subjected to potassium-induced CA for 7.5 minutes whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 ppm NO for 23 hours. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4 of 13), depressed neurological and left ventricular function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24 hours after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23 hours starting 1 hour after CPR attenuated neurological and left ventricular dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11 of 13; P=0.003 versus mice breathing air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum nitrate/nitrite levels. Deficiency of the α1 subunit of soluble guanylate cyclase, a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR. CONCLUSIONS: These results suggest that NO inhalation after CA and successful CPR improves outcome via soluble guanylate cyclase-dependent mechanisms.

A Cross-Sectional Study of the Impact of Pain Severity on Absenteeism and Presenteeism Among Japanese Full-Time Workers.

INTRODUCTION: Pain is known to have a high impact on work performance, but there are several confounding factors, such as stress and mental issues. Little is known about the impact of pain severity on work performance when adjusted for such confounding factors. The aim of this study was to identify the effect of pain severity on absence from work (absenteeism) and reduced performance (presenteeism). METHODS: A cross-sectional study was conducted among full-time workers at an industrial manufacturing company in Japan. Participants were assessed using a self-reported questionnaire, including work performance evaluations, pain characteristics, pain-related fear, psychological distress, stress at the workplace and home, workaholism, and self-awareness. Principal component analysis was utilized to decrease the dimensions of the measures, and orthogonal rotation was performed on identified components with an eigenvalue > 1.0. Multivariable logistic regression analyses were performed to determine the association between pain severity and absenteeism and presenteeism, and were adjusted for confounding factors. We also analyzed the association between pain intensity and presenteeism using multivariable logistic regression analyses. RESULTS: A total of 349 workers participated in the study. Six principal components were identified as confounding factors: work stress, regulation, mental instability, less support, home stress, and life dissatisfaction. Multivariable logistic regression analyses showed significant associations of moderate to severe pain with absenteeism (p = 0.02) and low and high presenteeism (p = 0.004 and 0.009, respectively), adjusted for age, sex, body mass index, short sleep, and the six principal components. Pain intensity was also significantly associated with low and high presenteeism (p = 0.002 and 0.014, respectively) in people with pain. CONCLUSIONS: Pain severity is a risk factor for absenteeism and presenteeism, even if workers have comorbid psychological stress or mental health problems.

Improvement in Disability Mediates the Effect of Self-Efficacy on Pain Relief in Chronic Low Back Pain Patients with Exercise Therapy.

Background: The biopsychosocial mechanism by which exercise leads to improvement in chronic low back pain (CLBP) remains unstudied. This prospective cohort study was performed to examine the effectiveness of exercise on pain, disability, and psychological status for CLBP. We also tested path analytic models in which changes in these variables were included. Methods: CLBP patients who visited the Interdisciplinary Pain Center of Keio University Hospital from July 2018 to April 2020 were included. The propensity score matching was performed between patients who underwent exercise (the exercise group) and those who did not (the control group). At the first visit and at the 3-month follow-up, pain (Numerical Rating Scale (NRS)), disability (Pain Disability Assessment Scale (PDAS)), and psychological status (Pain Self-Efficacy Questionnaire (PSEQ), and Pain Catastrophizing Scale (PCS)) were assessed. Changes in pain and disability at the follow-up were compared between the groups. The relationships between changes in pain, disability, and psychological variables were examined using Pearson's correlation and mediation analysis. Results: A significantly larger decrease in the PDAS was observed in the exercise group (N = 49) than in the control (N = 49) (p < 0.05). Increased PSEQ scores were significantly correlated with decreased NRS scores in both groups. In the exercise group, decreased PDAS fully mediated the relationship between increased PSEQ and decreased NRS (P < 0.05). Conclusion: Exercise improved disability, and the improved disability by exercise mediated the effect of increased self-efficacy on pain relief in CLBP patients.

[Risk management in regional anesthesia: spinal epidural hematoma].

Spinal epidural hematoma following neuraxial anesthesia is a rare condition that usually presents with acute and, if any, progressive neurological symptoms including pain, sensory/motor impairment, and bladder/ rectal disturbance. Although possible pathogenesis is mainly considered to be a direct injury of Batson's venous plexus, preoperative coagulation status and anticoagulant therapy also play some role in its development. Therefore, to prevent such a disastrous complication, one must choose an appropriate anesthetic technique and monitor neurological function of the patient at a regular time interval. In addition, it is highly recommended to carefully follow the recently revised regional anesthesia guideline for the patient receiving antithrombotic or thrombolytic therapy, although we still need further understanding and investigation of the complexity around this issue.

Association of work performance and interoceptive awareness of 'body trusting' in an occupational setting: a cross-sectional study.

OBJECTIVES: Work performance has been known to be influenced by both psychological stress (mind) and physical conditions (body). The aim of this study was to investigate the association between work performance and 'body trusting', which is a dimension of interoceptive awareness representing mind-body interactions. METHODS: A cross-sectional study was conducted among a sample of workers in an industrial manufacturing company in Japan. Participants were assessed with a self-reported questionnaire including evaluations of work performance, body trusting, psychological distress, pain persistence, workplace and home stressors, and workaholism. Participants' sociodemographic, health and lifestyle characteristics were collected from their annual health check data. The association between work performance and body trusting was examined using multivariable regression analyses in the overall sample and in a subsample of people with pain. RESULTS: A total of 349 workers participated in the study. A significant association between work performance and body trusting was observed, with higher body trusting representing higher work performance. The association was significant after controlling for psychological distress, workplace and home stress, workaholism and participants' characteristics (p<0.001). Compared with people without pain (n=126, 36.1%), people with pain (n=223, 63.9%) showed less body trusting, which was associated with decreased work performance after controlling for pain-related variables (p<0.001). CONCLUSIONS: Workers with higher body trusting showed higher work performance, even after controlling for various influencing factors. Body trusting may be an important target to promote work performance and to prevent loss of performance induced by health problems.

Effectiveness of Duloxetine for Postsurgical Chronic Neuropathic Disorders after Spine and Spinal Cord Surgery.

STUDY DESIGN: This is a retrospective observational study with an outpatient setting. PURPOSE: This study aimed to describe the effects of duloxetine (DLX) administration for postsurgical chronic neuropathic disorders (both pain and numbness) following spinal surgery in patients without depression. OVERVIEW OF LITERATURE: Although several reports indicated the potential of DLX to effectively treat postoperative symptoms as a perioperative intervention, there have been no reports of its positive effect on postsurgical chronic neuropathic disorders. METHODS: A total of 24 patients with postsurgical chronic pain and/or numbness Numeric Rating Scale (NRS) scores of ≥4 were enrolled. All patients underwent spine or spinal cord surgery at Keio University Hospital and received daily administration of DLX for more than 3 months. The mean postoperative period before the first administration of DLX was 35.5±57.0 months. DLX was administered for more than 3 months at a dose of 20, 40, or 60 mg/day, and the degree of pain and numbness was evaluated using the NRS before administration and 3 months after administration. Effectiveness was defined as more than a 2-point decrease in the NRS score following administration. RESULTS: In terms of the type of symptoms, 15 patients experienced only numbness, eight experienced both pain and numbness, and one experienced only pain. Of the 24 patients, 19 achieved effective relief with DLX. DLX was effective for all patients with postsurgical chronic pain (n=9), and it reduced postsurgical chronic numbness in 18 of 23 patients. No significant difference was observed in background spinal disorders. DLX was not effective for five patients who complained only of postsurgical chronic numbness. CONCLUSIONS: This study reports the effectiveness of DLX for postsurgical chronic neuropathic disorders. Although DLX reduced postsurgical chronic pain (efficacy rate=100%) and numbness (78.3%) in certain patients, further investigation is needed to determine its optimal use.

[Postoperative analgesia for hepatic cryosurgery].

BACKGROUND: Hepatic cryosurgery is an alternative therapeutic choice for patients who are not eligible for surgical liver resection. As this procedure sometimes causes postoperative bleeding tendency, we investigated indication of intravenous patient-controlled analgesia (IVPCA) after this surgery. METHODS: We measured pre- and postoperative platelet counts, coagulation profile and postoperative pain with IVPCA in 8 patients. RESULTS: Platelet counts decreased from 9.83 +/- 5.38 (x 10(3) x ml(-1)) to 5.91 +/- 4.56 (x10(3) x ml(-1)) postoperatively (P<0.01) and the maximum relative decrease was 72%. Platelet counts reached the maximum depression from 1 to 3 POD and in two patients it did not recover by 7 POD. Percentage of prothrombin activity decreased from 79.5 +/- 10.4 to 65.9 +/- 13.2 (P<0.01), with the nadir observed from 0 POD to 2 POD. In this study it was difficult to predict the extent of postoperative bleeding tendency beforehand. IVPCA with morphine provided adequate analgesia at rest. Althogh pain on moving seemed rather difficult to treat in two patients, IVPCA also helped patients walk with VAS score less than 55 mm in other patients. CONCLUSIONS: Considering the risk of bleeding tendency and epidural hematoma, we recommend IVPCA with opioid for postoperative pain in patients after hepatic cryosurgery instead of epidural analgesia and non-steroidal anti-inflammatory drugs.

Retraction Note: Desflurane anesthesia worsens emergence agitation in adult patients undergoing thyroid surgery compared to sevoflurane anesthesia.

The Editor-in-Chief has retracted this article [1]. The ethics committee approval was granted for an observational study and the need for patient consent was waived. However, the study design described is a randomized controlled trial and therefore patient consent should have been obtained. All authors agree with this retraction.