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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.

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.

Supplemental material, sj-pdf-1-mpx-10.1177_1744806921999924 for Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia by Daisuke Nishizawa, Masako Iseki, Hideko Arita, Kazuo Hanaoka, Choku Yajima, Jitsu Kato, Setsuro Ogawa, Ayako Hiranuma, Shinya Kasai, Junko Hasegawa, Masakazu Hayashida and Kazutaka Ikeda in Molecular Pain

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion., Video abstract

Except for neurotrophin, no drug had an indication for postherpetic neuralgia (PHN) in Japan prior to pregabalin approval. This approval might have changed PHN treatment patterns. This study aimed to compare PHN treatment patterns and medical costs between patients who started treatment before and after pregabalin approval. Japanese claims data were used to identify patients aged 18 years or more with PHN, postherpetic trigeminal neuralgia or postherpetic polyneuropathy who were initiated on their first PHN-associated prescription through May 2010 (before approval) or from June 2010 (after approval). From these claims, 6-month treatment patterns from first prescription were compared for the periods before and after approval. These patterns included pain-related medications and the frequency of pain-relief procedures. All-cause and pain-related medical costs were also compared for these periods. The number of PHN patients who were initiated on treatment before and after approval were 107 (mean age, 47.4 ± 13.0 years) and 505 (45.9 ± 13.0), respectively. Post-approval, significant reductions were observed for prescription of non-steroidal anti-inflammatory drugs, tricyclic antidepressants and neurotrophin relative to before approval. Excluding pregabalin acquisition costs, mean costs per patient for medications associated with PHN for 6 months from the first prescription were significantly lower after approval, ¥2882 vs ¥4185. Total medical costs were similar in both periods. Approval of pregabalin appeared to result in a treatment paradigm toward use of an approved therapy with demonstrated efficacy.

Limited research exists to support the extrapolation of the analgesic efficacy of pregabalin from one neuropathic pain condition to another. This retrospective analysis evaluated similarities in the efficacy of pregabalin for treating neuropathic pain associated with post-herpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI) in a Japanese population, as a basis for considering the extrapolation of these data to other neuropathic pain conditions.Data were analysed across pregabalin doses within each pain condition, from three comparable 13- to 16-week, randomized, double-blind, placebo-controlled trials (RCTs) and the corresponding 52-week, open-label extension trials of pregabalin in Japanese patients with PHN, DPN or SCI. Efficacy outcomes in the RCTs included endpoint and weekly mean pain and sleep interference scores; endpoint proportions of responders in pain; Patient Global Impression of Change scores; and 36-Item Short Form Health Survey (SF-36) scores or Hospital Anxiety and Depression Scale (HADS) assessments. Study discontinuation rates were compared between treatment groups. The extension trials assessed pain intensity, using the Short-Form McGill Pain Questionnaire.In the RCTs for all pain conditions, significant improvements in comparison with placebo in mean pain and sleep interference scores were evident after 1 week with pregabalin and were sustained throughout the treatment periods (p0.05). At the study endpoint, in comparison with placebo, a significantly greater percentage of pregabalin-treated patients experienced a ≥30 % reduction in pain across the RCTs (p0.05), and pregabalin significantly improved six of 16 SF-36 subscale scores in the PHN and DPN trials (p0.05). In the SCI trial, pregabalin-treated patients had numerically better outcomes of HADS scores. In the extension trials, improvements in pain intensity were maintained over a 52-week period.Similarities in the pregabalin efficacy profiles, including time to onset and magnitude of response, were confirmed regardless of the neuropathic pain condition. These data support the potential for extrapolating analgesic efficacy to other neuropathic pain conditions. CLINICALTRIALS.NCT00394901, NCT00553475, NCT00407745, NCT00424372, NCT00553280, NCT01202227.

BackgroundHuman 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.ResultsAlthough 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.ConclusionsThese 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.

It is unknown whether flumazenil antagonizes the decrease in cerebral blood flow or the alteration in dynamic cerebral autoregulation induced by midazolam. We, therefore, investigated the effects on cerebral circulation of flumazenil administered after midazolam, to test our hypothesis that, along with complete reversal of sedation, flumazenil antagonizes the alterations in cerebral circulation induced by midazolam.Sixteen healthy young male subjects received midazolam followed by flumazenil. The modified Observer's Assessment of Alertness/Sedation (OAA/S) scale and bispectral index (BIS) were used to assess levels of sedation/awareness. For evaluation of cerebral circulation, steady-state mean cerebral blood flow velocity (MCBFV) was measured by transcranial Doppler ultrasonography. In addition, dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between mean arterial pressure (MAP) variability and MCBFV variability.During midazolam sedation, defined by an OAA/S score of 3 (responds only after name is called loudly and/or repeatedly), BIS, steady-state MAP, steady-state CBFV, and transfer function gain decreased significantly compared with baseline. After flumazenil administration, an OAA/S score of 5 (responds readily to name spoken in a normal tone) was confirmed. Then, BIS and MAP returned to the same level as baseline. However, steady-state MCBFV showed a further significant decrease compared with that under midazolam sedation, and the decreased transfer function gain persisted.Contrary to our hypothesis, the present results suggest that despite complete antagonism of the sedative effects of midazolam, flumazenil would not reverse the alterations in cerebral circulation induced by midazolam.

BACKGROUND:In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-i

Introduction The mechanism of complex regional pain syndrome (CRPS) was reported as being related to both the central and peripheral nervous systems. Recurrence of CRPS was, reportedly, induced by hand surgery in a patient with upper limb CRPS. However, there is no documentation of mechanical allodynia and burning abdominal pain induced by Cesarean section under spinal anesthesia in patients with upper limb CRPS. Case We report the case of a patient who suffered from burning abdominal pain during Cesarean section under spinal anesthesia 13 years after the occurrence of venipuncture-induced CRPS of the upper arm. The patient's pain characteristics were similar to the pain characteristics of her right arm during her previous CRPS episode 13 years earlier. In addition, mechanical allodynia around the incision area was confirmed after surgery. We provided ultrasound-guided rectus sheath block using 20 mL of 0.4% ropivacaine under ultrasound guidance twice, which resulted in the disappearance of the spontaneous pain and allodynia. Discussion The pain relief was probably related to blockade of the peripheral input by this block, which in turn would have improved her central sensitization. Conclusion Our report shows that attention should be paid to the appearance of neuropathic pain of the abdomen during Cesarean section under spinal anesthesia in patients with a history of CRPS.

Two well-studied conditions of peripheral neuropathic pain are postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Several pregabalin trials for peripheral neuropathic pain have been conducted in the West, but limited data are available for Japan. As ethnicity may influence health risks, differences may be evident in safety data from pregabalin trials in Japan and in the West. The objectives of this review were to compare large pooled safety data from randomized controlled trials evaluating pregabalin for the treatment of PHN or DPN in the West with data from two (one PHN, N = 371; one DPN, N = 314) similar trials in Japan. Longer-term safety data from Japanese open-label extension studies were also reviewed in these neuropathic pain populations. Published and unpublished Pfizer-supported pregabalin trials were identified and sourced from internal Pfizer records. A PubMed search to check for inclusiveness was conducted on 2 November 2011 using the following criteria: 'diabetic peripheral neuropathy' OR 'postherpetic neuralgia' OR 'neuropathic pain' AND 'pregabalin', with limits set for clinical and randomized controlled trials published in English. Five PHN trials (N = 1250) and nine DPN trials (N = 2554) were identified as suitable for inclusion based on methodological comparability. Descriptive safety data from the original trials were reviewed and the most commonly reported adverse events (AEs; dizziness, somnolence, peripheral oedema and weight gain) were identified to be of primary interest. The majority of AEs were of mild to moderate severity in Japanese and Western populations. The most commonly reported AE data (all-causality) with pregabalin (regardless of dose) in Japan (dizziness: PHN = 31.1%; DPN = 24.6%, and somnolence: PHN = 28.6%; DPN = 25.7%) were compared with pooled data from the Western trials (dizziness: PHN = 24.9%; DPN = 23.0%, and somnolence: PHN = 15.1%; DPN = 13.4%). Further assessment of these pooled AE (all-causality) data showed that dizziness and somnolence appeared early in the course of pregabalin treatment, but resolved before the end of the treatment in the majority of PHN and DPN patients (maximum duration of trials was 13 weeks). The slightly higher incidence of dizziness and somnolence in the two Japanese trials than that seen in the Western trials may reflect an increased exposure to pregabalin per fixed dose due to the lower mean bodyweight of the Japanese versus Western populations (on a mg/kg basis). However, of the participants who experienced these AEs (all-causality), the proportion who withdrew from the trials in Japan (dizziness: PHN = 23.5%; DPN = 18.2%, and somnolence: PHN = 10.3%; DPN = 10.9%) were comparable with the proportion who withdrew from trials in the West (dizziness: PHN = 16.0%; DPN = 29.3%, and somnolence: PHN = 19.4%; DPN = 34.2%). In Japan, 12.5% (PHN) and 15.1% (DPN) of patients experienced peripheral oedema as an AE (all-causality) compared with 8.8% (PHN) and 10.3% (DPN) in the West. Weight gain as an AE (all-causality) was experienced in 11.7% (PHN) and 13.4% (DPN) of patients in Japan compared with 3.8% (PHN) and 7.0% (DPN) in the West, but stabilized with continued treatment. Despite the lower mean bodyweight in Japanese versus Western patients, the PHN and DPN patients in Japan had stable blood glucose and HbA(1c) levels throughout the trials. The results of this review indicate safety outcomes in pregabalin trials are comparable between patients in Japan and those in the West. While managing peripheral neuropathic pain with pregabalin treatment, all patients should be observed closely for the incidence of dizziness and somnolence, especially at the beginning of treatment. These patients should also be monitored for evidence of peripheral oedema and weight gain during stable treatment, regardless of the source of neuropathic pain.

Background Increasing age is associated with a longer duration of action of neuromuscular block. The aim of this study was to determine the influence of ageing on the recovery of the post-tetanic count (PTC) from rocuronium-induced neuromuscular block. Methods Twenty-two younger (20–60 years) and 22 older (> 70 years) patients were enrolled in this study. After induction of anaesthesia with fentanyl and propofol, all patients initially received 1 mg/kg rocuronium and neuromuscular block were evaluated by contractions of the adductor pollicis muscle to ulnar nerve train-of-four stimulation using an acceleromyograph. Subsequently, intense rocuronium-induced block was determined every 6 min using the PTC during 1.0–1.5% sevoflurane and remifentanil anaesthesia. When the first response to the PTC stimulus was detected, 0.2 mg/kg rocuronium was additionally administered, and again, spontaneous recovery of neuromuscular function was monitored until the first response to the PTC reappeared. Results Median values (range) of the times from the administration of 1 mg/kg and 0.2 mg/kg rocuronium until recovery of the first detectable PTC were significantly longer in the older [51.0 (27–100) min, P

腰下肢痛を訴えてペインクリニックを訪れる患者は増加しており，報道から情報を得て，エピドラスコピ－を希望する高齢者も多い．今回，85歳以上の2症例に本手術を施行した．いずれも，主訴は両側腰痛，両足のしびれが主であり，腰椎MRIで腰部脊柱管狭窄症が認められた．手術所見では，両者とも癒着が強く，強力な癒着剥離が必要であった．術後，1症例は痛みとしびれのため，他の1症例は下肢脱力のため，回復に時間を要したが，腰痛は改善し，両者とも満足度は高かった．85歳以上の高齢者にエピドラスコピーを施行する際には，十分な説明のもと，病態，患者の置かれた環境などを鑑みて適応を決めること，また手術を丁寧に施行することが重要である．

Background The aim of this study was to evaluate the correlation between cardiac output (CO) and reversibility of rocuronium-induced moderate neuromuscular block with sugammadex in elderly patients. Methods Fifty elderly (≥ 65 years) patients were enrolled in this study. During 1.0–1.5% end-tidal sevoflurane and remifentanil anaesthesia, contraction of the adductor pollicis muscle in response to ulnar nerve stimulation was acceleromyographically quantified. All patients initially received 1 mg/kg rocuronium followed by 0.2 mg/kg whenever the second twitch T2 of the train-of-four (TOF) response reappeared. CO was measured throughout the study using a FloTrac™/Vigileo™ monitor. After completion of surgery and at the reappearance of T2, the time required for a bolus dose of 2 mg/kg sugammadex to facilitate recovery to a TOF ratio of 0.9 was recorded, and its correlation with CO was analysed. Results Adequate recovery of neuromuscular block was achieved after sugammadex in all patients. Mean CO at the time of reversal with sugammadex was 5.3 l/min (1.3), and recovery time to a TOF ratio of 0.9 was 173.4 s (54.8). A statistically significant inverse correlation was seen between the time to recovery to a TOF ratio of 0.9 and CO [reversal time (s) = −27.7·CO + 298.7, R2 = 0.461, P

To describe a case of complete neurological recovery from cauda equina syndrome lasting ten months following spinal anesthesia with 0.5% hyperbaric bupivacaine and epidural anesthesia with ropivacaine, and to discuss the possible mechanisms involved.A 79-yr-old man with Paget's disease was scheduled for surgery to remove a skin tumour below his scrotum. He had no history of radicular pain or back pain and no pre-existing neurologic disorder. Surgery was performed with the patient in the supine position. He received 0.5% hyperbaric bupivacaine intrathecally for the procedure and ropivacaine through an epidural catheter for postoperative pain management. After catheter removal, the patient developed urinary retention, fecal incontinence, and perianal hypoesthesia. A lumbosacral magnetic resonance imaging (MRI) revealed no tumour, infarction, degeneration, spinal stenosis, or compression on the cauda equina nerve roots. A diagnosis of cauda equina syndrome was made, and the etiology was thought to be toxicity of bupivacaine either alone or in combination with ropivacaine. After three months, the patient reported some return of sensation at the perianal area, with complete resolution at four months. At the ten-month follow-up visit, the patient had recovered from his urinary retention and fecal incontinence.This case suggests that spinal anesthesia, even with an ordinary dose of hyperbaric 0.5% bupivacaine, might induce cauda equina syndrome in older patients.

国際疼痛学会が痛みを，「実際に組織損傷が起こったか，あるいは組織損傷の可能性のあるとき，またはそのような損傷を表す言葉によって述べられる不快な感覚と情動体験」と定義しているように，痛みという感覚はあくまで主観的なものであることから，これを客観的に評価，定量化することが困難である．しかし，臨床の場面では患者の訴える痛みにつき少しでも適切に評価する必要がある．そのために行う方法として，痛みを適正に評価するための条件，痛みのスケール，機器を用いる方法，脳画像診断，薬理学的疼痛機序判別試験について解説した．今後，より客観的な評価法の開発が求められる．

The aim of this study was to investigate whether monitoring neuromuscular block at the masseter muscle (MM) would allow faster tracheal intubation when compared with that at the adductor pollicis muscle (APM).Twenty female patients undergoing gynecological surgery were enrolled into this study. Immediately after inducing anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in a 2 Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with the anesthesiologist's left hand lifting the patient's jaw and holding an anesthesia facemask, while those of the APM were visually observed. Immediately after the contracting responses of the muscles were confirmed, all of the patients received an iv bolus of vecuronium 0.1 mg kg(-1). Onset times after vecuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. When the contraction of the MM could no longer be felt, the conditions for laryngoscopy and tracheal intubation were assessed.Onset time evaluated tactually at the MM (mean +/- SD, 108.4 +/- 27.7 s) was significantly shorter than that evaluated visually at the APM (181.2 +/- 32.1 s, P0.0001). The intubating conditions for all patients were graded as either excellent or good.Tactual evaluation of muscle paralysis of the MM during induction of anesthesia is clinically useful since it leads to faster tracheal intubation.

Classification of pain and their mechanisms are described in this chapter. Pain is classified into three categories according to the mechanisms; these are nociceptive pain, neuropathic pain and psychological pain. Nociceptive pain is caused by tissue damage and accompanies inflammation. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. Psychological pain is pain that is particularly attributable to the thought process, emotional state, or personality of the patient in the absence of an organic or delusional cause or tension. The characteristics of these different types of pain and methods of pain assessment are also described.

痛みは主観的な感覚であり, その測定・評価は難しい. 痛みの強さの測定についても, visual analogue scale (VAS) など, これまでにいくつかの評価法が提示されているが, いずれも主観的な測定法であった. この度, 患者がもつ痛みを, 痛みを伴わない異種感覚に置き換えて定量評価する知覚・痛覚定量分析装置が考案された. これにより, より客観的に痛みの強さを測定することができ, 患者間の痛みの強さや, ある患者の長期にわたる痛みの強さの比較・検討が可能になると考える. VASと比較した臨床データの一部を提示する.

Background Dexmedetomidine, which is often used in intensive care units in patients with compromised circulation, might induce further severe decreases in cerebral blood flow (CBF) with temporal decreases in arterial pressure induced by various stimuli if dynamic cerebral autoregulation is not improved. Therefore, the authors hypothesized that dexmedetomidine strengthens dynamic cerebral autoregulation. Methods Fourteen healthy male subjects received placebo, low-dose dexmedetomidine (loading, 3 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.2 microg x kg(-1) x h(-1) for 60 min), and high-dose dexmedetomidine (loading, 6 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.4 microg x kg(-1) x h(-1) for 60 min) infusions in a randomized, double-blind, crossover study. After 70 min of drug administration, dynamic cerebral autoregulation was estimated by transfer function analysis between arterial pressure variability and CBF velocity variability, and the thigh cuff method. Results Compared with placebo, steady state CBF velocity and mean blood pressure significantly decreased during administration of dexmedetomidine. Transfer function gain in the very-low-frequency range increased and phase in the low-frequency range decreased significantly, suggesting alterations in dynamic cerebral autoregulation in lower frequency ranges. Moreover, the dynamic rate of regulation and percentage restoration in CBF velocity significantly decreased when a temporal decrease in arterial pressure was induced by thigh cuff release. Conclusion Contrary to the authors' hypothesis, the current results of two experimental analyses suggest together that dexmedetomidine weakens dynamic cerebral autoregulation and delays restoration in CBF velocity during conditions of decreased steady state CBF velocity. Therefore, dexmedetomidine may lead to further sustained reductions in CBF during temporal decreases in arterial pressure.

In Japan, the attitudes of the public and the medical profession have created problems with regard to the management of pain, especially the use of opioid analgesics. Japan Partners Against Pain (JPAP(R)) was formed in 2003 by a small group of concerned physicians who wanted to change the attitudes of the medical profession and the general public by providing education and information. JPAP has grown rapidly from its initial 11 members to over 1,700 members in 2007, almost half of whom are doctors, while most of the remainder are nurses or pharmacists. Under the title of 'Pain Academy', JPAP provides lectures and seminars for the health care professions based on a special slide kit that was developed for education about pain management. JPAP also provides information and seminars for patients, their families, and the general public, as well as media briefings. It publishes booklets for patients and a quarterly newsletter for members, and runs two popular websites (one for members only and one for the public). Furthermore, JPAP sets up information booths at conferences on pain management, and has established a special support network for palliative care teams. Over the next 5 years, JPAP hopes to continue and expand such activities, so that eventually all Japanese realize that pain can, and should, be treated effectively.

A novel transdermal matrix patch delivery system for fentanyl has been developed to deliver improved management of cancer pain compared with that obtained using current fentanyl reservoir patches. This study was carried out to assess the efficacy, safety and pharmacokinetic profiles of a 12.5 microg/h transdermal matrix fentanyl patch administered with the objective of replacing morphine, oral oxycodone or fentanyl injection formulations. The study also evaluated how the pharmacokinetic profiles of higher dose fentanyl patches (25, 37.5 and 50 microg/h) changed following dose adjustments to optimize management of cancer pain.This open-label, multicentre study involved 87 patients of both sexes (or =20 years) with a confirmed diagnosis of cancer. Patients were receiving any one of the following at the time of enrollment for the management of their cancer pain: (a) morphine45 mg/day orally,30 mg/day as suppositories, or15 mg/day by injection; (b) oral oxycodone30 mg/day; or (c) fentanyl injectable preparations0.3 mg/day. The patients were administered a 3-day course of fentanyl transdermal matrix patch application three times. The initial dose was 12.5 microg/h, which could be increased when a new patch was applied if the physician deemed this to be appropriate based on pain intensity ratings and use of rescue medications. Efficacy outcomes included patients' global assessment scores (primary efficacy endpoint) measured on a five-step scale and dichotomous scores for physicians' global assessment. The occurrence of adverse events and changes in laboratory tests were evaluated as safety variables. Serum fentanyl levels were measured immediately after removal of the old patch on days 4, 7 and 10 to obtain data on trough serum concentrations.The percentage of patients in category 3 or higher (very satisfied, satisfied, or neither satisfied nor dissatisfied) for the patient's global assessment score was 89.4% (76/85), indicating high patient satisfaction and attainment of sufficient pain control after patients switched from their previously used opioid analgesics. Similar findings were obtained on physicians' global assessment scores. A total of 316 adverse events occurred in 78 (90.7%) of 86 patients who were administered at least one patch. These included nausea (31 [36.0%]), somnolence (26 [30.2%]), vomiting (22 [25.6%]), diarrhoea (17 [19.8%]), constipation (14 [16.3%]), pyrexia (11 [12.8%]) and insomnia (9 [10.5%]). The mean (+/- SD) serum fentanyl concentration determined on day 4 was 169.9 +/- 103.4 pg/mL (n = 83). Serum fentanyl measurement results indicated that the same fentanyl patch dose resulted in similar serum fentanyl levels, while increased doses produced higher serum fentanyl concentrations.The fentanyl matrix transdermal patch formulation employed in this study demonstrated sufficient cancer pain control for patients switching from morphine or oral oxycodone preparations. The patch tested was well tolerated and its use did not result in any increased incidence of adverse drug reactions over those commonly found with opioid analgesics.

Objectives: Several studies have demonstrated the advantages of epiduroscopy versus conservative therapies for low back pain with few studies evaluating the results in operated and non-operated back patients. We compared the effects and complications of epiduroscopy between these patients. Patients and methods: A multi-institutional, prospective, clinical study was performed in 183 patients whose low back and leg pain had failed to respond to conservative therapies. Patients were divided into an operated back (Op) group and a non-operated (Non-op) group. Japanese Orthopedic Association (JOA) score, the Japanese version of the Roland-Morris Disability Questionnaire (JRMDQ) scores, and 100-mm visual analogue scales (VAS) for leg pain, leg numbness, low back pain and dissatisfaction with ADL were recorded before and at 1 month and 3 months after epiduroscopy. Results: All scores significantly improved at 1 month and 3 months after epiduroscopy in both groups. JOA scores in the Non-op group were sign...

Study Objective To evaluate the different effects on autonomic circulatory control during volatile induction/maintenance of anesthesia (VIMA) vs total intravenous anesthesia (TIVA). Design Prospective study. Setting Operating theater of a university hospital. Patients Twenty patients, with American Society of Anesthesiologists physical status of I or II, were randomly allocated into the VIMA group (n = 10) or the TIVA group (n = 10). Interventions In the VIMA group, anesthesia was induced with 5% sevoflurane and 60% N 2 O in oxygen and maintained with 2% sevoflurane and 60% N 2 O in oxygen. In the TIVA group, anesthesia was induced with propofol 2.0 mg/kg intravenously by bolus injection and fentanyl 2 μg/kg, and maintained with an intravenous infusion of propofol 5 mg/kg·per hour and air-oxygen mixture. Measurements Monitoring included recordings of electrocardiographic and arterial blood pressure waveforms. Autonomic nervous activity and arterial cardiac baroreflex function were evaluated by analysis of blood pressure variability, heart rate variability, and transfer function analysis between these 2 variables. Main Results In the VIMA group, the low-frequency component of blood pressure variability (LF SBP ) and low- and high-frequency components of the R-R interval variability (LF RR and HF RR ) decreased significantly during anesthesia. In the TIVA group, LF SBP and LF RR decreased significantly. The degree of reduction in LF SBP was greater in the VIMA group than in the TIVA group. However, changes in R-R interval variability and cardiac baroreflex indices were not significantly different between the 2 groups. Conclusions Our results demonstrated that although reductions in autonomic nervous modulation to the heart might not be so different between the 2 groups, reduction in sympathetic nervous modulation to peripheral vasculature is greater in the VIMA group than in the TIVA group.

A S b ORONARY ARTERY FISTULA (CAF) is an infrequent vascular anomaly that establishes a direct link between a arge subepicardial coronary artery and a cardiac chamber, ajor vessels, or other vascular structures. Although coronary rteriography remains the gold standard for the diagnosis of AF, it is not always possible to reveal the complete delineaion of CAF including its origin, course, and drainage. A case f left main CAF originating directly from the aorta is reported n which preoperative coronary arteriography failed to identify he site of drainage and intraoperative transesophageal echoardiography (TEE) was used to identify the precise location of rainage. Scheduled surgical repairs included closure of the rigin of the CAF (the left main coronary orifice from the aorta) nd closure of the drainage of the CAF combined with coronary rtery bypass graft (CABG) surgery to the left anterior decending artery and the circumflex artery. In this particular ase, the left anterior descending artery and the circumflex rtery were not scheduled for closure at their origins from the eft main CAF to keep the circulation available for the other eeding arteries to the left ventricle (LV) that might originate rom the CAF. Therefore, intraoperative TEE was also essential or confirmation of absence of fistulous flow and regional wall otion abnormalities of the LV.

The aim of the present study was to clarify the neurophysiological changes associated with analgesic and behavioral effects of low-dose ketamine HCl in patients suffering from chronic neuropathic pain. Ten in-patients with neuropathic pain participated in this single-blind, placebo-controlled study after giving written informed consent. Following intravenous injections of a saline solution (placebo), three bolus injections of 5 mg ketamine HCl were administered at 5 min intervals. Changes in pain perception were assessed using a numerical rating scale for pain. Behavioral changes, including psychotomimetic effects, were assessed using the Brief Psychiatric Rating Scale (BPRS). Electroencephalograms (EEG) and electrooculograms (EOG) were recorded continuously throughout the testing period. One minute EEG and closed-eye eye movements were quantified. The effects of ketamine were evaluated by comparing the neurophysiological and behavioral parameters obtained from the placebo and ketamine trials. Pain reduction was significantly correlated with ketamine-induced changes in hallucinatory behavior and excitement as measured by the BPRS. Ketamine injections caused a significant decrease in the EEGα amplitude without an accompanying reduction in EEG frequency. The EEGα amplitude reduction at the right central electrode was significantly related to subjective pain relief. Subanesthetic doses of ketamine significantly decreased rapid eye movements, but did not initiate slow eye movements. In conclusion, the present EEG-EOG/behavioral results indicate that ketamine-induced failure of neural integration between cortical–subcortical regions induces psychotic symptoms and alters pain perception on neuropathic pain.

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.

Background: During partial neuromuscular blockade indirect repetitive nerve stimulation causes fade in the response of the muscle. We studied the intensity of the fade induced by intravenous administration of three steroidal muscle relaxants, and investigated the mechanism of fade by comparing with results obtained during partial blockade with animal toxins and vesamicol. Methods: In 60 cats, we measured the fade in the compound action potentials of the gastrocnemius muscle evoked by repetitive sciatic nerve stimulation at 100 Hz during partial neuromuscular blockade with rocuronium, vecuronium, pancuronium, α-bungarotoxin, μ-conotoxin and vesamicol, respectively. Results: Profound fade was induced by all three non-depolarising muscle relaxants (rocuronium=vecuronium

平成元年1月から平成6年5月までに,静脈注射や採血時などに注射針による神経損傷が原因で発生したと考えられる疼痛および知覚障害を主訴として当院ペインクリニック科を受診した患者6例について調査,検討した.穿刺部位では手関節橈側,肘関節屈側,示指部であった.症状としては火傷様疼痛,しびれ,冷感などを訴えhypesthesia, allodyniaなどの知覚障害が認められた.神経損傷によるinjury dischargeや炎症による侵害刺激伝播を抑制するため,損傷部への局所麻酔薬浸潤や抗炎症薬が有用であった.医療従事者へ対する患者の不満も痛みを長引かせる重要な因子であり,発生直後からの適切な対処が必要であると思われた.

Objective. The purpose of this study was to determine the incidence and prognosis of persistent and neuropathic pain induced by venipuncture for blood sampling in clinical practice. Design & Setting. We investigated the incidence of persistent and neuropathic pain after venipuncture for blood sampling and evaluated the prognosis of patients with neuropathic pain at Nihon University Itabashi Hospital, Japan, based on an observational study. Subjects. Outpatients who required venipuncture for blood sampling at the laboratory room of Nihon University Itabashi Hospital between 2004 and 2008 were included as study subjects. Results. In the present study, of the 587,551 venipunctures performed at our hospital between 2004 and 2008, the incidences of persistent and neuropathic pain after venipuncture were 1 in every 4,418 venipunctures (133/587,551) and 1 in every 30,923 venipunctures (19/587,551), respectively. All the 19 patients who were identified as having neuropathic pain recovered completely. Conclusions. We demonstrated that the incidence of persistent pain after venipuncture for blood sampling is low and that its prognosis is good.

We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation changes in subjects undergoing cesarean section under spinal anesthesia (SP) with hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I, 15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within 20 min after SP were significantly lower than the baseline values. In contrast, there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in group I after SP. Total-Hb and MBP in group H were significantly lower than those in group I within 10 min after SP. There was no significant change of deoxy-Hb, tissue oxygen index, or heart rate from baseline in either of the groups. These results suggest that isobaric bupivacaine may be superior to hyperbaric bupivacaine for preventing a decrease of maternal cerebral blood flow after SP for cesarean section.

We used near-infrared spectroscopy (NIRS) to evaluate cerebral blood oxygenation changes in subjects undergoing cesarean section under spinal anesthesia (SP) with hyperbaric bupivacaine (group H, 27 subjects) or isobaric bupivacaine (group I, 15 subjects). In group H, total-Hb, oxy-Hb, and mean blood pressure (MBP) within 20 min after SP were significantly lower than the baseline values. In contrast, there was no significant change from baseline in total-Hb, oxy-Hb, or MBP in group I after SP. Total-Hb and MBP in group H were significantly lower than those in group I within 10 min after SP. There was no significant change of deoxy-Hb, tissue oxygen index, or heart rate from baseline in either of the groups. These results suggest that isobaric bupivacaine may be superior to hyperbaric bupivacaine for preventing a decrease of maternal cerebral blood flow after SP for cesarean section.

The twitch responses evoked from the abductor hallucis muscle (AHM) and the adductor pollicis muscle (APM) were examined simultaneously in 20 anesthetized patients following a single bolus intravenous administration of 0.04 mg·kg−1 of vecuronium bromide. The mean onset time of vecuronium-induced depression of AHM twitch responses was significantly slower than that of APM twitch responses (4.9±1.5 minvs 3.7±1.2 min, mean±SD,P