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Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 ( PAR2 / F2RL1 ) and interleukin 17A ( IL-17A / IL17A ) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case-control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine., Competing Interests: The authors declare no conflict of interest.

Chronic pain is reportedly associated with the transient receptor potential canonical 3 ( TRPC3 ) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.

Background: Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain., Results: Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain ( p  ≥ 1.858 × 10 -7 ), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p  = 1.638 × 10 -7 ). In the additional gene-based analysis, one gene, PRKCQ , was significantly associated with chronic pain in the trend model (adjusted p  = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models., Conclusions: These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

Acute pain that is associated with herpes zoster (HZ) can become long-lasting neuropathic pain, known as chronic post-herpetic neuralgia (PHN), especially in the elderly. HZ is caused by the reactivation of latent varicella-zoster virus (VZV), whereas PHN is not attributed to ongoing viral replication. Although VZV infection reportedly induces neuronal cell fusion in humans, the pathogenesis of PHN is not fully understood. A genome-wide association study (GWAS) revealed significant associations between PHN and the rs12596324 single-nucleotide polymorphism (SNP) of the heparan sulfate 3- O -sulfotransferase 4 ( HS3ST4 ) gene in a previous study. To further examine whether this SNP is associated with both PHN and VZV reactivation, associations between rs12596324 and a history of HZ were statistically analyzed using GWAS data. HZ was significantly associated with the rs12596324 SNP of HS3ST4 , indicating that HS3ST4 is related to viral replication. We investigated the influence of HS3ST4 expression on VZV infection in cultured cells. Fusogenic activity after VZV infection was enhanced in cells with HS3ST4 expression by microscopy. To quantitatively evaluate the fusogenic activity, we applied cytotoxicity assay and revealed that HS3ST4 expression enhanced cytotoxicity after VZV infection. Expression of the VZV glycoproteins gB, gH, and gL significantly increased cytotoxicity in cells with HS3ST4 expression by cytotoxicity assay, consistent with the fusogenic activity as visualized by fluorescence microscopy. HS3ST4 had little influence on viral genome replication, revealed by quantitative real-time polymerase chain reaction. These results suggest that HS3ST4 enhances cytotoxicity including fusogenic activity in the presence of VZV glycoproteins without enhancing viral genome replication.

Background: Pre-anaesthesia hypertension (PAH) occurs when the blood pressure (BP) in patients before surgery, in the operating room, before anaesthesia induction, temporally elevates regardless of normal ambulatory recorded BP or self-measured BP at home. PAH might be caused by anxiety and mental stress about the anaesthesia and surgery. We know that most of the patients with sustained hypertension (SH) are elders, males, obese subjects, and dyslipidaemic subjects. Furthermore, most of the patients with white coat hypertension, which is caused by mental stress about the medical environment of an outpatient, clinic, and hospital ward, are elders, females, and non-smokers. In the present study, we investigated some relevant clinical characteristics influencing PAH., Methods: Sampling data on patients more than 20 years old, who underwent consecutive operations under general, intrathecal, or epidural anaesthesia were retrospectively collected from hospital records and anaesthesia records. Hospital-room hypertension (HH) was defined as systolic BP (sBP) greater than or equal to 140 mm Hg in the hospital room before anaesthesia and surgery. Operating-room hypertension (OH) was defined as sBP greater than or equal to 140 mm Hg in the operating room before anaesthesia induction., Results: 112 and 119 patients belonged to the OH and operating-room normotension (ON) groups, respectively. The OH group members were significantly older than the ON group members. Body mass index in the OH group was significantly greater than in the ON group. The proportions of males, dyslipidaemic subjects, and non-smokers in the OH group were significantly higher than in the ON group. In the logistic regression analysis, age, body mass, dyslipidaemia, and HH were selected as significant factors that contribute independently to OH (odds ratios; 1.045, 1.031, 2.912, and 4.354, respectively)., Conclusions: The clinical characteristics of the patients with OH are: elders, obese subjects, dyslipidaemic subjects, and hospital-room hypertensive subjects. Ageing, obesity, dyslipidaemia, and HH are clinical risk factors relating to PAH.

Objectives: Minimally invasive epiduroscopy has recently been reported as an effective treatment procedure for chronic and intractable low back pain. However, no study has determined safe anesthetics for monitored anesthesia care during epiduroscopy. We aimed to compare and evaluate conventional monitored anesthesia care drugs with dexmedetomidine., Methods: A retrospective study including all patients who underwent epiduroscopy at the JR Tokyo General Hospital from April 2011 to March 2016 was designed. The epiduroscopy procedures were performed under anesthesia with dexmedetomidine plus fentanyl (dexmedetomidine group) or droperidol plus fentanyl (neuroleptanalgesia group). Patients who received analgesics other than fentanyl, another analgesic combined with fentanyl, any sedative other than dexmedetomidine or droperidol, or who had incomplete data were excluded. We compared (1) the type and dose of medication during the epiduroscopy and (2) the incidence of postoperative nausea and vomiting., Results: We identified 45 patients (31 and 14 in the dexmedetomidine and neuroleptanalgesia groups, respectively) with a mean age of 69.0 years. The two groups had comparable characteristics, such as age, sex, body mass index, the American Society of Anesthesiologists Physical Status, analgesics used in the clinic, comorbidities, history of smoking, and the duration of anesthesia. The dexmedetomidine group received a significantly lower fentanyl dose during surgery (126 ± 14 vs 193 ± 21 µg, mean ± standard deviation, p = 0.014) and exhibited a significantly lower incidence of postoperative nausea and vomiting (1 vs 3, p = 0.047) than the neuroleptanalgesia group., Conclusion: This study involved elderly patients, and the use of dexmedetomidine in monitored anesthesia care during epiduroscopy procedures in these patients may reduce the required fentanyl dose during surgery and the incidence of postoperative nausea and vomiting. This strategy may help prevent respiratory depression and aspiration., Competing Interests: Declaration of conflicting interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure-time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I-IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I-IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I-IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I-IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I-IV.

Methods of pain treatment are various because of different mechanisms and causes of pain. However, we should recognize complications and side effects of these methods of pain treatment. In addition, we should understand the prevention and management of these complications and side effects. If patients develop side effects during pain treatment they may hesitate to continue to receive pain treatment. We must avoid these situations. In this special issue, the prevention and management of complications and side effects of pain treatment are described including nerve block such as stellate ganglion block, epidural block and nerve root block, and interventional methods such as spinal cord stimulation, thermocoagulation and pulse radiofrequency. Concerning drugs, opioid, non-opioid analgesics, antidepressants and anticoagulant are also discussed.

Background: Myocardial contraction and relaxation are regulated by increases and decreases in cytoplasmic calcium concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase and the second half of the descending phase of the [Ca(2+)]i transient curve better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to analyse the first half of the descending phase of CaTC (CaTCIII)., Methods: The [Ca(2+)]i was measured using the Ca(2+)-sensitive aequorin, which was microinjected into 15 isolated mouse left ventricular (LV) papillary muscles. The observed CaTCIII data in the interval from the point corresponding to the peak [Ca(2+)]i to the point corresponding to dCa/dtmin was curve-fitted using the h-L and m-E function equations by the least-squares method., Results: The mean correlation coefficient (r) values of the h-L and m-E function best curve-fits for 11 CaTCIIIs were 0.9986 and 0.9982, respectively. The Z transformation of h-L r (3.64 ± 0.45) was larger than that of m-E r (3.50 ± 0.33) (p < 0.05)., Conclusions: The h-L function can evaluate most CaTCIIIs more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. The three calculated h-L parameters i.e., amplitude constant, time constant, and non-zero asymptote, are more reliable indices than m-E for evaluating the magnitude and time course of the change in the decrease in [Ca(2+)]i., Key Words: Ca(2+) transient; Half-logistic amplitude constant; Half-logistic non-zero asymptote; Half-logistic time constant; Myocardial Ca(2+) handling.

Taking EMLA cream and Penles tape 18 mg as examples, this article describes the conditions for skin penetration of topical anesthetics, with their onset time of action, duration of effect and a precautions for their use. EMLA cream is a unique cream for topical anesthesia which is the eutectic mixture of lidocaine and propitocaine to increase skin penetration. The safety study demonstrated that blood concentrations of active ingredients of EMLA cream were below toxic levels. EMLA cream, with confirmed high skin penetrability and safety, should be used for pain reduction of various treatments for many diseases. Here in Japan, EMLA cream has indications not only for pain reduction of skin laser therapy but also for reduction of needle puncture pain. This means the use of topical anesthesia would be expanded to wider ranges of treatments.

Chronic intractable pain is difficult to manage as the mechanisms of chronic pain are complicated. Recently rehabilitation is used in patients with chronic pain not responding to NSAIDs, non-opioids, anti-depressants and so on. Rehabilitation includes acute, recovery and maintained modes of rehabilitation. This review is focused on the concept of rehabilitation, rehabilitation therapy, rehabilitation during recovery period, nerve rehabilitation, music-trampoline therapy and so on.

This article describes the first events of general anesthesia in the world by Tokumei Takamine in 1698 and Seishu Hanaoka in 1804, the establishment of anesthesiology in Japan including the meaning of a scientific society, the establishment of Japanese Society of Anesthesiologist and Department of Anesthesiology at University of Tokyo, past contributions to anesthesiology by Japanese anesthesiologists, and contributions to anesthesiology by Journal of Anesthesia and the Japanese Journal of Anesthesiology.

The article describes an analysing device that measures the perception and intensity of pain quantitatively. While it is not necessarily true that psychological aspect is totally irrelevant to pain measurement, this device is remarkable in that it is capable of measuring the intensity of pain felt by the patient more objectively by using electric stimuli. The feature of this device is that it uses a non-pain heteresthesia for measuring the intensity of pain. The device is compact, light-weight, and portable. Unlike VAS that requires only a scale, the device requires a person to carry out the measurement. Nevertheless, as the National Health Insurance (NHI) coverage has been approved, introduction of the device may be facilitated in terms of budget for the purchase and labor. The device is useful to better understand not only the intensity of pain but also the pathological conditions, resulting in more appropriate treatment, by (1) comparing degree of pain or VAS values taken by a multicenter study with those of a patient; (2) using both degree of pain and VAS; and (3) multiple measurements of degree of pain and VAS in one case.

New diagnostic and therapeutic devices for patients with chronic intractable pain are used in Japan. The following articles describe topics of new diagnostic and therapeutic devices for patients with chronic intractable pain including thermography, functional MRI, device for the quantitative analysis of perception and pain sensation, epiduroscopy, device for phototherapy, Racz catheter and device for spinal cord stimulation (SCS).

Recently, new drugs for intractable chronic pain are available in Japan. The following articles describe topics of new drugs for intractable chronic pain including transdermal fentanyl, tramadol/acetaminophen combination tablets, buprenorphine transdermal patch, pregabalin, and duloxetine. Treatment of constipation in chronic pain patients and management of opioid induced nausea and vomiting are also described to prevent complication of pain-relief drug therapy.

Background: Myocardial contraction and relaxation are regulated by increases and decreases in intracellular cytoplasmic calcium (Ca(2+)) concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase (CaTI) and the second half of the descending phase of the [Ca(2+)]i transient curve (CaTIV) better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to the analysis of the second half of the ascending phase of the [Ca(2+)]i transient curve (CaTII)., Methods: The [Ca(2+)]i transient was measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into 15 isolated left ventricular (LV) papillary muscles of mice. The observed CaTII data during the time duration from the point corresponding to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dtmax) to the point corresponding to the peak Ca(2+) concentration was curve-fitted by the least-squares method using the h-L and m-E function equations., Results: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for CaTII were 0.9996 and 0.9984, respectively. The Z transformation of h-L r was larger than that of m-E r (p < 0.0001). H-L residual mean square (RMS) was smaller than m-E RMS (p < 0.001)., Conclusions: The h-L function tracks the magnitudes and time courses of CaTII more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. Compared with the m-E time constant, the h-L time constant of CaTII is a more reliable index for evaluating the time duration of the change in the increase in [Ca(2+)]i during the combination of the middle part of the contraction process and the early part of the relaxation process. CaTII can be assessed by the h-L function model in cardiac muscles. The h-L approach may provide a more useful model for studying each process in myocardial Ca(2+) handling., Key Words: Calcium handling; Calcium transient; Curve-fit; Half-Logistic function; Time constant.

We should take care of the occurrences of apnea and hypopnea after emergence from general anesthesia in the children with sleep apnea syndrome (SAS) due to an increase in sensitivity to opioid agonists given for previous recurrent hypoxia. Preoperative assessment for SAS with apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum artery oxygen saturation by pulse oxymetry (lowest SpO2) obtained from polysomnography (PSG) test could help to predict the postoperative respiratory depression. In perioperative management in the children with SAS who are candidates for adenotonsillectomy, the dose of opioid agonists during anesthesia maintenance for purpose of postoperative analgesia and sedation should be reduced; postoperative respiratory and circulatory management with monitoring of respiratory movement of the thoracoabdominal part, and electrographic (ECG) and SpO2 monitoring should be continued intensively under long-term oxygen administration; and airway management, nasal continuous positive airway pressure (nCPAP), and artificial ventilation should be prepared for the occurrence of postoperative respiratory depression.

The following articles describe topics of phototherapy including low reactive laser therapy by diode laser device, semiconductor as a medium consisting of aluminum, gallium and arsenic, near infrared light irradiator using halogen lamp, and xenon light by high-intensity electrical stimulation of xenon gas. In addition, the applications of phototherapy in the clinical medicine such as rehabilitation, orthopedics and pain clinic are described. Phototherapy is a useful and safe method for pain relief.

Purpose: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono-exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure., Methods: Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations., Results: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse., Conclusion: The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents.

Cancer pain is very unpleasant often difficult to treat. Therefore, we should recognize the mechanisms of cancer pain and know the physical pain, psychological pain, social pain and spiritual pain as total pain. Besides, we must understand how to evaluate the cancer pain using the methods of assessment of cancer pain, and scales of pain degree (VAS, NRS, VRS, FRS, FVAS). New devices of pain measurement and the character of pain(McGill and Yatabe) are also introduced. The mechanism and grade of cancer pain often confuse us to recognize cancer pain. The articles in this special issue are useful for the evaluation and treatment of cancer pain. I feel happy if these articles contribute to the treatment of patients with cancer pain.

This chapter describes physical pain including pain, anorexia-cachexia syndrome, nausea-vomiting, abdominal distention, ascites, constipation and dyspnea. In effect, patients are more likely to present with several concurrent symptoms. Each of these symptoms is described separately in this chapter.

Pentazocine is a widely used mixed agonist-antagonist opioid. Previous animal studies have demonstrated that pentazocine-induced antinociception displayed a ceiling effect characterized by biphasic dose response with a increasing and then descending analgesia like a bell-shaped curve. This study attempted to clarify the mechanisms underlying such dose-response relationships. ddY and C57BL/6J mice received subcutaneous injection of saline or pentazocine (3, 10, 30, 56, or 100 mg · kg(-1)), at 120 min after subcutaneous injection of saline, a μ-opioid receptor antagonist clocinnamox mesylate (C-CAM) (5 mg · kg(-1)), a κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) (10 mg · kg(-1)), or the combination of C-CAM and nor-BNI. The antinociceptive effects of pentazocine were evaluated using tail pressure, hot plate, tail flick, and acetic acid writhing tests. Without pretreatment with an opioid receptor antagonist, the antinociceptive effects of pentazocine exhibited biphasic bell-shaped dose-response curves peaking at 30 mg · kg(-1). C-CAM completely and partly antagonized the antinociception induced by pentazocine at low (3-30 mg · kg(-1)) and high (56-100 mg · kg(-1)) doses, respectively. nor-BNI enhanced the antinociception by pentazocine at high doses and turned the later descending portion of the biphasic dose-response curves into a sigmoid curve. The combination of C-CAM and nor-BNI completely abolished the antinociception by pentazocine at all doses. Our results suggest pentazocine produces antinociception primarily via activation of μ-opioid receptors, but at high doses, this μ-opioid receptor-mediated antinociception is antagonized by concomitant activation of κ-opioid receptors. This provides the first reasonable hypothesis to explain the ceiling effects of pentazocine analgesia characterized by a biphasic dose response.

Intravenous patient-controlled analgesia (IV-PCA) using opioids such as morphine and fentanyl can be an effective analgesic method for post-operative pain that is resistant to conventional administration of narcotic analgesics and nonsteroidal anti-inflammatory drugs, and where epidural block and peripheral nerve block are not feasible. In addition to post-operative pain relief, IV-PCA can facilitate early ambulation, reduce respiratory complications, and increase patient satis-faction. However, respiratory and circulatory depression, and post-operative nausea and vomiting (PONV) often occur as side effects of IV-PCA with opioids. Administration of droperidol can be an effective treatment for PON.

Agitation during the emergence from general anesthesia is a great post-operative problem that often injures the patients themselves and requires the medical staff to restrain and calm the patients. The predisposing factors for emergence agitation include anesthesia, operation, and patient. Sevoflurane anesthesia results in higher incidence of emergence agitation than halothane, because of the rapid emergence, and its effects on central nervous system inducing convulsion and post-operative behavioral changes. The otorhinolaryngologic and ophthalmologic surgeries, post-operative pain, young age, pre-operative anxiety, no past surgical history, and adjustment disorder of patients are risk factors for emergence agitation. The change from sevoflurane to propofol during anesthesia maintenance is a contributing factor to reduce incidence of emergence agitation. The medications including opioids, midazolam, alpha-2 agonists, ketamine, non-steroidal anti-inflammatory drugs, nitrous oxide, and propofol, and aggressive nerve block such as caudal epidural block for post-operative sedation and analgesia are effective to avoid incidence of emergence agitation. The calm emergence following general anesthesia would decrease the self-injuring behavior, and enhance the parent and caregiver satisfaction in general anesthesia and surgery.

For religious reasons, Jehovah's Witnesses do not accept homologous blood transfusions. Instead, they request alternative medical care that does not involve such transfusions. A 58-year-old woman, a Jehovah's Witness, was scheduled for pancreaticoduodenectomy for pancreatic carcinoma under general and epidural anesthesia. She presented with hemoglobin (Hb) concentration of 10.3 g x dl(-1) and hematocrit (Ht) of 31.5% preoperatively. She was fully informed about the risk of cardiac arrest and postoperative complications without blood transfusion, and consented to the bloodless surgery with infusion of colloid solutions; albumin and hydroxyethylated starch, and intraoperative, salvaged, autologous blood transfusion. She submitted a signed letter, absolutely refusing homologous blood transfusion and releasing the hospital from any liability. The general anesthesia was induced using fentanyl, propofol, and vecuronium, and maintained with sevoflurane and vecuronium in combination with epidural anesthesia using lidocaine and fentanyl. An autologous blood transfusion device was prepared for use in the event of massive intraoperative hemorrhage. The pancreaticoduodenectomy and cholecystectomy were performed without the necessity of starting the intraoperative, salvaged, autotransfusion. The volume of intraoperative hemorrhage was 1,108 ml. Lactated Ringer's solution 3,300 ml, physiological saline 200 ml, and hydroxyethylated starch 500 ml were infused during the operation. Although her postoperative Hb and Ht dropped to 8.7 g x dl(-1) and 26.8%, respectively, no transfusion was performed. Anesthesiologists should respect the demands of Jehovah's Witnesses, and should attempt to manage surgery without transfusion.

Background: The efficacy and safety of a fentanyl-containing patch formulated for 1-day application at the initiation and during continuous treatment of cancer pain were evaluated in patients previously untreated with opioid analgesics., Methods: In the dose-titration period (Period I), the 1-day formulation (0.84 mg x day(-1)) was applied for 2 days. If pain relief was insufficient, the dose was titrated, and the success rate was evaluated. In the double-blind period (Period II), the efficacies of the 1-day and the 3-day formulations for pain control were compared., Results: The dose-titration success rate of the 1-day formulation was 80.6%, and its analgesic effect was comparable to that of the 3-day formulation. Moreover, tolerability of the 1-day formulation was good. Adverse events occurring in the patients were those generally seen after treatments with opioid analgesics, and severe symptoms were also reported., Conclusions: Dose titration of the 1-day formulation was accomplished in a short period in patients with cancer pain who had been previously untreated with opioid analgesics; the efficacy of the formulation for pain control after repeated dosing was comparable to that of the 3-day formulation, and its tolerability was good. However, it was considered that the 1-day formulation should be used in patients with good tolerability to opioid analgesics. Further, for safety reasons, the dose should not be increased for at least 2 days after the initial application and the last dose increase.

Background: In patients with moderate to severe cancer pain receiving treatment with opioid analgesics, the treatment was switched from the existing opioid analgesic to the 1-day fentanyl patch (the "1-day formulation"), and the efficacy and safety of the 1-day formulation were evaluated., Methods: The preceding opioid analgesic therapy was switched to therapy with the 1-day formulation, at a dose level corresponding to the daily dose level of the preceding opioid analgesic. The pain control rate was evaluated 10 days after the treatment switch. The dose level of the 1-day formulation was kept unchanged for the first 2 days after the treatment switch., Results: The pain control rate with the 1-day formulation was 81.8% (54/66 patients). In 57.6% (38/66) of patients, the treatment switch to a low-dose 1-day formulation (0.3 or 0.6 mg x day(-1)) yielded sustained pain control. The adverse reactions to the 1-day formulation observed in this study were similar to those previously reported for the Durotep MT Patch (the "3-day formulation"). No severe adverse reactions, such as respiratory depression, were noted in the present study. Thus, the 1-day formulation was well-tolerated., Conclusions: In patients with moderate to severe cancer pain, switching of opioid analgesic therapy to 1-day formulation therapy has been shown to be safe and useful, following rotation from other opioids, for controlling cancer pain. The demonstrated utility was similar to that associated with the 3-day formulation.

Neuropathic pain, as a chronic intractable pain, is well known to be difficult in prevention, diagnosis and treatment. Especially, neuropathic pain from different causes has each characteristics for prevention, diagnosis and treatment. These include post-herpetic pain, persistent chronic pain following traffic accident, pain after peripheral nerve injury in venipuncture, phantom limb pain originating from dysfunction of the primary motor cortex, pain from failed back surgery syndrome, and diabetic neuropathy, and are helpful for understanding prevention, diagnosis and treatment of neuropathic pain.

Aim of the Study: Shu-jing-huo-xue-tang (SJHXT) (Japanese name: Sokei-kakketu-to), a traditional Chinese herbal medicine composed of 17 crude drugs, has been prescribed over hundreds of years for treatment of chronic pain syndromes. We evaluated if oral SJHXT could suppress neuropathic pain behaviors in rats with chronic constriction injury (CCI) of the sciatic nerve., Materials and Methods: (1) Rats received repeated oral SJHXT 0.5 or 1.0 g/kg once daily for 14 days starting 24 h after CCI surgery, while neuropathic manifestations were evaluated until day 20 post-CCI. (2) Other groups of rats received single oral SJHXT 1.0 g/kg on day 14 post-CCI. (3) Additional groups of rats received oral SJHXT 1.0 g/kg on day 14 post-CCI, concomitantly with intraperitoneal yohimbine 1 mg/kg or methysergide 5 mg/kg. Neuropathic manifestations, including mechanical allodynia and thermal hyperalgesia, were evaluated with paw withdrawal responses to increasing mechanical pressure and radiant heat, respectively., Results: Mechanical allodynia and thermal hyperalgesia developed by day 14 post-CCI. Repeated oral SJHXT for 14 days produced anti-allodynic and anti-hyperalgesic effects that outlasted the period of drug administration. Single oral SJHXT on day 14 also produced significant anti-allodynic and anti-hyperalgesic effects, which were inhibited by yohimbine, an alpha-2 adrenoceptor antagonist, but not by methysergide, a serotonin receptor antagonist., Conclusions: Oral SJHXT produced anti-hypersensitivity effects by actions on alpha-2 adrenoreceptors in CCI-neuropathic rats, and chronic oral administration of SJHXT could produce the long-lasting anti-hypersensitivity effects., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

In tracheal intubation assisted by tube-guiding devices passing through the tube, such as fiberoptic scopes, bougies, tracheal tube exchange catheters, and light wands, passage of the tube-guiding device, by itself, is often easy. But advancing a tracheal tube with a conventional distal tip over these tube-guiding devices is frequently difficult or impossible, because its rigid, side-beveled tip frequently catches on anatomical features of the airway. A novel tracheal tube, the Parker Flex-Tip tube (Parker Medical, Colorado, USA) has a centered, curved, tapered and flexible distal tip that passes through the airway faster and easier than conventional tracheal tubes. As it is advanced along a tube-guiding device, the tip of the Parker tube travels along the midline of the airway, without the gap that usually exists between the distal edge of a conventional tracheal tube and the tube-guiding device. The gapless, midline travel of the Parker tube leads to a greater incidence of first-attempt intubation success with tube-guiding devices, because there is less risk of tube tip hang-ups on the arytenoids and the vocal cords. Clinically, use of the Parker tube is helpful for oral and nasal intubations, especially in patients with difficult airways.

Half-logistic (h-L) function, which is half of the sigmoidal, logistic function with a boundary at the inflection point, curve-fits the isovolumic relaxation left ventricular (LV) pressure curve from the minimum of the first order time derivative of pressure (dP/dt(min)), and the myocardial isometric relaxation tension curve from the minimum of the first order time derivative of tension (dF/dt(min)) superior to the conventional mono-exponential function. Recently, we found that h-L function could curve-fit the other partial curves. The isovolumic LV pressure curve in the excised, cross-circulated canine heart, was divided into four distinct phases with boundaries set at the maximum of dP/dt (dP/dt(max)), peak LV pressure, dP/dt(min), and LV end-diastolic pressure (LVEDP) resulting in the first phase from the point corresponding to QR on the electrocardiogram to dP/dt(max); the second phase from dP/dt(max) to the peak LV pressure; the third phase from the peak LV pressure to dP/dt(min); and the fourth phase from dP/dt(min) to LVEDP. Similarly, the isometric twitch tension curves in the mouse LV and rabbit right ventricular (RV) papillary muscles were divided into four distinct phases with boundaries set at the maximum of dF/dt (dF/dt(max)), peak tension, dF/dt(min), and resting tension resulting in the first phase from the point corresponding to twitch stimulation to dF/dt(max); the second phase from dF/dt(max) to the peak tension; the third phase from the peak tension to dF/dt(min); and the fourth phase from dF/dt(min) to resting tension. The h-L correlation coefficient (r) values for the sequential curves were larger than the m-E r values, respectively, and the h-L residual mean squares (RMS) were smaller than the m-E RMS values, respectively. The h-L time constants are indices which quantify cardiac and myocardial inotropism and lusitropism more accurately. We consider that the h-L approach also applies for evaluation of the isovolumic contraction phase and the isovolumic relaxation phase in the beating hearts.

Pain, a very unpleasant feeling often difficult to treat, is the most common complaint of patients visiting hospital. When a patient with pain visits our institution, first of all, we have to diagnose the pain including the grade of pain and stress associated with sympathetic-adrenal-medullary system. We then treat the pain of the patient using available devices. In the following special articles, functional magnetic imaging, device for measurement of salivary alpha-amylase and PainVisionTM for pain measurement are described as devices for diagnosis of pain. As devices for treatment of pain, epidural infuser pump, intrathecal infusion pump, spinal cord stimulation device and phototherapy device are also described. The mechanism and grade of intractable pain often confuse us to recognize pain. The devices, described in this special issue, are very useful for the evaluation and treatment of intractable pain. I feel happy if these articles greatly contribute to the treatment of patients with pain by pain clinicians.

Hyperventilation syndrome has often occurred as a reaction to anxiety and stress. We experienced hyperventilation syndrome before induction of and after awakening from general anesthesia. A 53-year-old woman with no central nervous and psychiatric disease was scheduled for left total hip arthroplasty under general and epidural anesthesia. After entering the operating room, she was breathing faster and deeper than necessary. She complained of dyspnea, and the numbness and sweating of her lower extremities. We found that she had the same experience on her dental treatment. We diagnosed her as preoperative hyperventilation syndrome. Twenty minutes after she had become relaxed, we could insert the lumbar epidural catheter, and tracheally intubate following anesthesia induction with fentanyl, thiopental, and vecuronium. Anesthesia was maintained using inhalation of sevoflurane and epidural anesthesia with ropivacaine. As end-tidal carbon dioxide (EtCO2) value was 18 mmHg after anesthesia induction, we controlled the ventilator to regulate EtCO2. The operation was finished in 54 minutes successfully without a special event. She was extubated because there was no clinical problems. The total anesthesia time was 2 hours and 4 minutes. Postoperatively in the recovery room, she breathed fast and complained of dyspnea and the numbness of her extremities again. The arterial blood gas analysis showed reduced arterial partial pressure of carbon dioxide tension with resulting respiratory alkalosis. We diagnosed her as postoperative hyperventilation syndrome. We let her breathe in and out of a vinyl bag continuously and injected antipsychotic medication haloperidol intravenously. After injection of haloperidol 3 mg for 30 minutes, she recovered from hyperventilation. Hyperventilation syndrome before general anesthesia could occur postoperatively again. We supposed that her hyperventilation syndrome is induced by anxiety and stress of operation before induction and again after awakening from general anesthesia. Haloperidol could be effective for repeated hyperventilation syndrome induced by psychogenic factors during perioperative period.

The waveforms of myocardial tension and left ventricular (LV) pressure curves are useful for evaluating myocardial and LV performance, and especially for inotropism and lusitropism. Recently, we found that half-logistic (h-L) functions provide better fits for the two partial rising and two partial falling phases of the isovolumic LV pressure curve compared to mono-exponential (m-E) functions, and that the h-L time constants for the four sequential phases are superior inotropic and lusitropic indices compared to the m-E time constants. In the present study, we tested the hypothesis that the four sequential phases of the isometric tension curves in mammalian cardiac muscles could be curve-fitted accurately using h-L functions. The h-L and m-E curve-fits were compared for the four phases of the isometric twitch tension curves in 7 isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The isometric tension curves were evaluated in the four temporal phases: from the beginning of twitch stimulation to the maximum of the first order time derivative of tension (dF/dt(max)) (Phase I), from dF/dt(max) to the peak tension (Phase II), from the peak tension to the minimum of the first order time derivative of tension (dF/dt(min)) (Phase III), and from dF/dt(min) to the resting tension (Phase IV). The mean h-L correlation coefficients (r) of 0.9958, 0.9996, 0.9995, and 0.9999 in rabbit and 0.9950, 0.9996, 0.9994, and 0.9997 in mouse for Phases I, II, III, and IV, respectively, were higher than the respective m-E r-values (P < 0.001). The h-L function quantifies the amplitudes and time courses of the two partial rising and two partial falling phases of the isometric tension curve, and the h-L time constants for the four partial phases serve as accurate and useful indices for estimation of inotropic and lusitropic effects.

Arrhythmia during general anesthesia occurrs occasionally as a result of the effect of inhalation anesthetic agent on cardiac conduction. We experienced a case of atrioventricular junctional rhythm (AVJR) during maintenance of general anesthesia with sevoflurane. A 61-year-old woman with normal preoperative electrocardiogram was scheduled for right total knee arthroplasty and autologous iliac crest bone graft under general and epidural anesthesia. After inserting the lumbar epidural catheter, endotracheal intubation was performed following anesthesia induction with fentanyl, thiopental, and vecuronium, and anesthesia was maintained using inhalation of nitrous oxide and sevoflurane, and epidural anesthesia with ropivacaine. Forty minutes after starting operation, the dissociated and upright P-wave approached the QRS complex, remaining within QRS complex for several beats, and then reappeared from it electrocardiographically. ST segment was transiently depressed from baseline. The R-R interval and waveform of the QRS complex did not change. The sequence was repeated. The blood pressure had been held slightly depressed but waveform of pulse oxymetry (SpO2) did not change during this phenomenon. We diagnosed it as AVJR, which is classified into isorhythmic dissociation. After discontinuation of sevoflurane at the end of the operation, isorhythmic dissociation returned to sinus rhythm. Sevoflurane could induce atrioventricular conduction disturbance leading to isorhythmic dissociation of AVJR. We should be aware that hypotension can result from isorhythmic dissociation during sevoflurane anesthesia.

A 39-year-old woman was diagnosed in infancy as suffering from Klippel-Trenaunay-Weber syndrome, affecting both her lower limbs. She had undergone, for several times, gastroepiploic transplantation at 18 years of age. She was scheduled for lymphaticovenular anastomosis of the right limb. Preoperatively, computed tomography showed no thrombosis in her lower limbs. We gave only general anesthesia, because of her strong anxiety, and concern of hemangioma and blood vessel malformation in epidural space. General anesthesia was induced with thiopental, fentanyl, and vecuronium, and maintained with nitrous oxide, oxygen and sevoflurane. Tourniquet had been used for only 30 minutes considering the risk of occurring deep vein thrombosis. Surgery was successfully finished in eight hours and thirty minutes. Using tourniquet increases the risk of deep vein thrombosis and pulmonary embolism. We should use tourniquet as briefly as possible to avoid the occurrence of pulmonary embolism. We recommend avoidance of epidural analgesia, as the patient may have hemangioma and arteriovenous malformation in epidural space, and we should evaluate them by magnetic resonance imaging before anesthesia.

We report anesthetic management of a patient with severe ovarian hyperstimulation syndrome (OHSS). A 33-year-old woman presented with severe abdominal acites and effusion after ovarian stimulation with HMG followed by ovulation induction with HCG. She was suspected of having intraabdominal hemorrhage because of ectopic pregnancy. Emergency laparotomy was performed under general anesthesia. Massive ascites and intraabdominal hemorrhage were observed and patient was treated by adequate fluid infusion and blood transfusion. Patient was treated with non-invasive positive pressure ventilation (NPPV) after operation and recovered. It is essential to maintain a correct balance of fluids, through appropriate intravenous infusion of crystalloids, albumin, blood transfusion and an adequate urine output. Further it is important to prevent thromboembolic event. Knowledge of the clinical features, complications and acute management of OHSS will permit the anesthesiologist to treat these patients in an optimal fashion.

As the left ventricular (LV) pressure curve and myocardial tension curve in heart are composed of contraction and relaxation processes, we have found that hybrid logistic (HL) function calculated as the difference between two logistic functions curve-fits better the isovolumic LV pressure curve and the isometric twitch tension curve than the conventional polynomial exponential and sinusoidal functions. Increase and decrease in intracellular Ca2+ concentration regulate myocardial contraction and relaxation. Recently, we reported that intracellular Ca2+ transient (CaT) curves measured using the calcium-sensitive bioluminescent protein, aequorin, were better curve-fitted by HL function compared to the polynomial exponential function in the isolated rabbit RV and mouse LV papillary muscles. We speculate that the first logistic component curve of HL fit represents the concentration of the Ca2+ inflow into the cytoplasmic space, the concentration of Ca2+ released from sarcoplasmic reticulum (SR), the concentration of Ca2+ binding to troponin C (TnC), and the attached number of cross-bridge (CB) and their time courses, and that the second logistic component curve of HL fit represents the concentration of Ca2+ sequestered into SR, the concentration of Ca2+ removal from the cytoplasmic space, the concentration of Ca2+ released from TnC, and the detached number of CB and their time courses. This HL approach for CaT curve may provide a more useful model for investigating Ca2+ handling, Ca(2+) -TnC interaction, and CB cycling.

Non-linear regression and curve-fitting may contribute to resolution of the mechanism, summarise information, remove noise, allow speculation regarding unmeasured data, and separate the effects of multiple factors. The isovolumic left ventricular (LV) pressure curve and isometric myocardial tension curve have been curve-fit with polynomial expotential and sinusoidal functions. The isovolumic LV pressure curve and myocardial isometric tension curve are composed of contraction and relaxation processes. We have proposed that hybrid logistic (HL) functions, calculated as the difference between two logistic functions, fit better the isovolumic LV pressure curves at any LV volume, heart rate, and infused calcium (Ca2+) concentration in coronary artery in the excised, cross-circulated canine heart, and the isometric twitch tension curves at any muscle length and extracellular Ca2+ concentration in the ferret right ventricular (RV) papillary muscle. We suggest that the six HL parameters are useful to evaluate the contraction and relaxation processes in the heart and myocardium. This HL approach for the isovolumic LV pressure curves and the isometric twitch tension curves may provide a more useful model for speculating Ca2+ handling, Ca(2+) -Troponin C interaction, and cross-bridge cycling.

Intractable chronic pain resists any therapy, and the mechanism of the pain varies from patient to patient even with the same disease. Therefore, patients with chronic pain tend to look for a doctor who would successfully attenuate their pain. Consequently, a patient may visit several doctors only to get similar treatments after wasting time and money. To avoid the situation, pharmacological classification (so called drug challenge test) to determine the mechanism of a patient's pain is conducted. Drugs tested are morphine, ketamine, lidocaine, thiopental, phentolamine, midazolam, ATP clomipramine, PGE1, and neurotropin. A test for each drug is conducted on a separate day. As each drug has a different pain-attenuating mechanism, mechanism of a patient's pain will be clarified when an effective drug is found. A drug is administered as a bolus several times or continuously intravenously. According to the results of our tests conducted in sixty-five patients with neuropathic pain due to peripheral nerve injuries, ketamine proves to be the most effective in alleviating pain followed by ATP, morphine and thiopental. Therapies based on the results were provided to the patients.

Chronic intractable pain is well known to be very difficult in management. The mechanisms of intractable chronic pain are complicated. Therefore, such a patient is often involved with multiple pain mechanisms and needs multiple drugs which have different types of analgesic actions. This new insight into pain mechanisms is important in the diagnosis and treatments of chronic intractable pain patients and the concept of balanced analgesia is widely accepted. Therefore, the evaluation of many factors which modulate the pain behavior is important. Opioids such as morphine and other analgesics are sometimes useful for the treatment of chronic intractable pain. Nerve blocks and interventional treatments are also helpful.

Aims: The association between SNPs of the human OPRM1 gene encoding the micro-opioid receptor and postoperative analgesic requirements in surgical patients remains controversial. Here, we evaluate whether any of the five tag SNPs (A118G, IVS2+G691C, IVS3+G5953A, IVS3+A8449G and TAA+A2109G) representing the four linkage disequilibrium blocks of the OPRM1 gene influences postoperative analgesic requirements., Materials & Methods: We studied 138 adult Japanese patients who underwent major open abdominal surgery under combined general and epidural anesthesia and received continuous postoperative epidural analgesia with opioids., Results: The 118G homozygous (GG) patients required 24-h postoperative analgesics more than 118A homozygous (AA) and heterozygous (AG) patients. Tag SNP haplotypes also were associated with 24-h postoperative analgesic requirements., Conclusions: These results suggest that OPRM1 gene tag SNP genotypes and haplotypes can primarily contribute to prediction of postoperative analgesic requirements in individual patients undergoing major open abdominal surgery.

Aim of the Study: In this study, we investigated the effects of processed Aconiti tuber (PAT), an oriental herbal medicine, at analgesic doses on acute morphine antinociception in morphine-naïve mice and morphine tolerance in morphine-tolerant mice., Materials and Methods: In acute experiments, mice received subcutaneous (s.c.) morphine (2, 5, or 10 mg/kg) and oral distilled water or PAT (0.3, 1.0, or 3.0 g/kg). The mechanical nociceptive threshold (MNT) and thermal nociceptive latency (TNL) were measured with the tail pressure test and tail flick test, respectively, before, and at 30, 60, 90, and 120 min after s.c. morphine injection. In chronic experiments, mice received s.c. morphine (10 mg/kg) and oral distilled water or PAT (0.3, 1.0, or 3.0 g/kg) once daily for 11 days. MNT was measured before, and at 60 min after, and TNL was measured before, and at 30 min after, daily morphine injections on days 1-11., Results: PAT at analgesic doses inhibited the acute antinociceptive effect of morphine dose-dependently in morphine-naïve mice. In contrast, PAT at analgesic doses potentiated the chronic antinociceptive effect of morphine dose-dependently by inhibiting the development of morphine tolerance dose-dependently. These effects of PAT on acute and chronic morphine antinociception were mediated through activation of kappa-opioid receptors., Conclusions: These results indicated that chronic co-administration of PAT at analgesic doses with morphine could provide better-maintained morphine analgesia in a long-term morphine treatment after initial inhibition of acute morphine antinociception for a brief period of time.

A 32-year-old man underwent subtotal thyroidectomy for Basedow's disease under general anesthesia. Preoperatively, the free thyroxine (fT4) and free triiodothyronine (fT3) levels were suppressed and thyroid stimulating hormone level was elevated with administration of iodine and propylthiouracil. Heart rate was 52 beats x min(-1) in sinus rhythm. General anesthesia was induced with fentanyl, propofol and vecuronium, and maintained with nitrous oxide, oxygen and sevoflurane. Systolic blood pressure was controlled within 100 and 130 mmHg. Rectal temperature was 36.5 degrees C after anesthesia induction, gradually rising at a range of 0.4 and 0.7 degrees C per hour, up to 38.6 degrees C four hours after the operation. Arterial blood gas showed bicarbonate 17.1 mEq x l(-1) and base excess -8.1 mmol x l(-1). The metabolic acidosis with normal anion gap lasted during and after the operation. We cooled his body with cold acetyl linger fluid and cooling mattress, and administered sodium bicarbonate. Heart rate increased to 96 beats x min(-1) before the end of operation. Subtotal thyroidectomy was finished in 5 hours 16 minutes. The amount of blood loss was 950 ml. Postoperatively, the serum fT4 and fT3 were suppressed. The serum creatine kinase and lactate dehydrogenase levels increased slightly. He did not show muscle rigidity and neurological disorders. We suspect that he has developed thyroid storm-like symptoms such as hyperthermia and tachycardia induced by subtotal thyroidectomy. Metabolic acidosis might be the result of distal tubular acidosis, which rarely accompanies Basedow's disease. Arterial blood gas analysis and urinalysis should be performed, preoperatively.

We experienced anesthesia care for two patients taking methylphenidate (Ritalin), which is a central nervous system stimulant of amphetamine analogues, usually administered for narcolepsy or refractory depression. The proper dose of methylphenidate is 20-60 mg per day. General anesthesia with epidural anesthesia was administered to both cases for total hip replacement. One patient could discontinue taking methylphenidate five days before the operation, but the other patient could not. Both cases needed more anesthetics than usual on induction, but very stable condition could be maintained during and after the operations. We consider that it is possible to perform general anesthesia safely for patients taking a usual dose of methylphenidate.

Brachial plexus injury has often occurred secondary to malposition of the patient during general anesthesia. We have experienced median nerve injury following laparoscopic sigmoidectomy. A 61-year-old man with diabetes and hypertension received laparoscopic sigmoidectomy under general and epidural anesthesia. Tracheal intubation was easy without excessive retroflextion of his neck after anesthesia induction with fentanyl, propofol, and vecuronium. Both his upper arms were abducted to 80 degrees and his elbows were extended on a padded arm board. The shoulder braces were placed over both his acromioclavicular joints. His head remained in neutral position. Anesthesia was maintained with air, oxygen, sevoflurane, fentanyl, and vecuronium using mepivacaine via epidural catheter. During surgical procedures, he was in a combined lithotomy and head down position at maximum of 20 degrees. The operative table was tilted to the right at maximum of 20 degrees. The operation was finished successfully in 2 hours and 40 minutes without a special event. Postoperatively, he complained of numbness of the first, second, and third digits, and the radial side of fourth digit in his right hand. The redness on both his shoulders was observed. Muscle weakness and motor disturbance were not observed. Orthopedic surgeon diagnosed him as right median nerve injury. His symptoms improved gradually by physical training and disappeared one week after the operation. We suspect that his right median nerve injury was caused by compression and stretching of the brachial plexus in head down position, right lateral tilt table, use of shoulder brace, laparoscopy, abduction of the upper arm, and extension of the elbow. In laparoscopic operation in head down position, we should avoid using the shoulder brace to minimize the risk of brachial plexus injury. The arms should be approximated to the sides as nearly as possible and the elbows should be gently flexed to unload the median nerve and relieve tension on the brachial plexus.

Intractable chronic pain is very difficult to treat. Nowadays, small amounts of drugs, that have different actions on the mechanism of pain relief are administered intravenously, and the effects of the test drugs on individual chronic pain patients are investigated by using the evaluation method of the visual analogue scale (VAS). This will enable elucidation of the mechanisms of pain in each chronic pain patient. Based on this information, drugs that are effective for the treatment of individual chronic pain patients can be prescribed. Drugs that are used for the drug challenge tests are phentolamine, barbiturate, morphine, lidocaine, ketamine, benzodiazepine, adenosine-3-phosphate (ATP), neurotropine, and prostaglandine E1. Phentolamine is effective for the management of sympathetically maintained pain. Barbiturate and morphine are effective for the treatment of deafferentation pain and nociceptive pain, respectively. Lidocaine is effective for the treatment of neuropathic pain; ketamine, for allodynia; and benzodiazepine, for anxiety-related pain. ATP exerts a positive effect in total pain management. Neurotropine and prostaglandine E1 are effective for the management of neuropathic pain and ischemic pain, respectively. These tests aid in the selection of drugs that maybe useful for the treatment of intractable chronic pain in patients.

In the previous studies, we demonstrated that an oriental herbal medicine, processed Aconiti tuber (PAT), at subanalgesic doses could inhibit or reverse the antinociceptive tolerance to morphine. In the present study, we compared the effect of PAT, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidin)cyclohexyl)-benzeneacetamide methane sulfonate hydrate (U50488H), a selective kappa opioid receptor (KOR) agonist, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine-maleate (MK-801), a N-methyl-D-aspartate (NMDA) receptor antagonist, on the antinociceptive tolerance to morphine in the same experimental condition. Mice received subcutaneous morphine (10 mg/kg), and oral PAT at a subanalgesic dose (0.3 g/kg for mechanical or 1.0 g/kg for thermal test), or intraperitoneal U50488H at a subanalgesic dose (3 mg/kg), or MK-801 at a subanalgesic dose (0.1 mg/kg) once daily for 14 days. The mechanical nociceptive threshold was measured before, and at 60 min by tail pressure testing, and thermal nociceptive latency was measured before, and at 30 min by hot plate testing, after daily morphine injections. PAT and U50488H could not only inhibit the development of morphine tolerance but also reverse the already-developed morphine tolerance, while MK-801 could only inhibit the development of morphine tolerance but not reverse the already-developed morphine tolerance, in both mechanical and thermal nociceptive tests. These data suggested that PAT, an indirect-acting KOR agonist, share the common pharmacological property of KOR agonists on morphine tolerance, and that PAT may be superior to some NMDA receptor antagonists which do not reverse already-developed morphine tolerance.

A decrease in intracellular calcium (Ca2+) concentration in the cardiac muscle is one of the important factors to induce myocardial relaxation. A mono-exponential (m-E) function has been used for assessing myocardial relaxation curve of isometric tension and intracellular calcium transient (CaT) decay, and the m-E time constants for the relaxation curve of isometric tension (F tau E) and CaT decay (Ca tau E) have been recognised as lusitropic indices. However, we found that a half-logistic (h-L) function fits the relaxation curve of isometric tension much more precisely than the conventional m-E function in the ferret right ventricular (RV) papillary muscle. Moreover, we demonstrated that the goodness of the h-L fits for CaT decays was superior to the goodness of the m-E fits in the rabbit RV and murine left ventricular papillary muscles. The changes in the h-L time constants for the relaxation curves of isometric tension (F tau L) and CaT decays (Ca tau L) with the different onsets were significantly smaller than the changes in F tau E and Ca tau E, respectively. The differences in the h-L non-zero asymptotes for the relaxation curves of isometric tension and CaT decays with the different onsets were smaller than the changes in the m-E non-zero asymptotes. The h-L function model characterises the amplitudes and time courses of the relaxation curve of isometric tension and CaT decay more precisely than the m-E function model, and thus F tau L and Ca tau L serve as more novel and reliable lusitropic indices. Simultaneous analysis of myocardial relaxation curve of isometric tension and CaT decay using h-L functions can become a useful method for assessment of myocardial calcium handling.