Outcomes of Pain Management Training for the Fourth- and Fifth-Year Medical Students.

Pain management is a major medical issue. However, current medical education in Japan is inadequate with regard to training students to properly assess patients with acute and chronic pain and plan their treatment. Therefore, starting in 2019, Hyogo Medical University established a multidisciplinary educational system to better train medical students to provide pain care. The course, called clinical pain study, is offered to fourth- and fifth-year medical students. Fourth-year students learn the scientific aspects of pain through clinical practice. In this study, we assessed students' understanding of pain management based on the results of pretests and posttests performed before and after their practicum. These tests were administered from November 2019 to April 2022 to 263 fourth- and fifth-year medical students who took the clinical pain study class. The test results were compared in terms of the percentage of correct answers and the total score for each question using McNemar's chi-square test and paired t-tests, respectively. The results showed a significant improvement in the mean of the total score, confirming the improvement in medical students' knowledge (6.43 vs. 7.35 points; p < 0.001). Based on the results, overall, pain education at the university has had positive outcomes and will therefore be continued in the future.

Validation of the Japanese version of the 8-item Chronic Pain Acceptance Questionnaire (CPAQ-8).

This study aimed to examine the reliability and validity of the Japanese version of the Chronic Pain Acceptance Questionnaire (CPAQ-8J). A total of 108 outpatients with chronic pain completed the CPAQ-8 questionnaire, along with the Acceptance and Action Questionnaire-II, Hospital Anxiety and Depression Scale, Pain Disability Assessment Scale, Numerical Rating Scale, and EuroQol 5 dimensions 5-level. Confirmatory factor analyses examined the factor structure. Results indicated that the CPAQ-8J comprised a two-component factor structure. Correlations between the CPAQ-8J and each variable were as expected, except between the "pain willingness" subscale and other scales ; thus, the CPAQ-8J had a certain degree of convergent validity. Internal consistency and test-retest reliability suggest that the CPAQ-8J is reliable. The psychometric properties of the CPAQ-8J meet a certain standard ; meanwhile, some issues must be addressed for its practical application. Further research should consider the influence of cultural characteristics in practical application. J. Med. Invest. 70 : 88-93, February, 2023.

Intraoperative Assessment of Surgical Stress Response Using Nociception Monitor under General Anesthesia and Postoperative Complications: A Narrative Review.

We present a narrative review focusing on the new role of nociception monitor in intraoperative anesthetic management. Higher invasiveness of surgery elicits a higher degree of surgical stress responses including neuroendocrine-metabolic and inflammatory-immune responses, which are associated with the occurrence of major postoperative complications. Conversely, anesthetic management mitigates these responses. Furthermore, improper attenuation of nociceptive input and related autonomic effects may induce increased stress response that may adversely influence outcome even in minimally invasive surgeries. The original role of nociception monitor, which is to assess a balance between nociception caused by surgical trauma and anti-nociception due to anesthesia, may allow an assessment of surgical stress response. The goal of this review is to inform healthcare professionals providing anesthetic management that nociception monitors may provide intraoperative data associated with surgical stress responses, and to inspire new research into the effects of nociception monitor-guided anesthesia on postoperative complications.

Imaging evaluation of continuous extrapleural intercostal nerve block for minimally invasive cardiac surgery: a case report.

BACKGROUND: Spinal nerve block is difficult with minimally invasive cardiac surgery (MICS), because of the risk of serious bleeding complications due to full heparinization. Continuous extrapleural intercostal nerve block (CEINB) is a postoperative pain treatment for intercostal thoracotomy, with fewer complications. Here, we report a case in which imaging evaluation of CEINB with contrast medium was conducted to anatomically confirm the spread of local anesthetics after MICS. CASE PRESENTATION: A 65-year-old woman with severe mitral regurgitation underwent mitral valve plasty under general anesthesia via right-sided mini-thoracotomy. A CEINB catheter was placed before the incision was closed, without creating a conventional extrapleural pocket. We conducted an imaging evaluation with a contrast medium via the inserted catheter and confirmed sufficient spread around the intercostal nerve area. In addition, postoperative pain was well controlled by the nerve block. CONCLUSIONS: Imaging evaluation of CEINB with contrast medium could increase analgesic quality and decrease complications post-MICS.

Pilot study of a basic individualized cognitive behavioral therapy program for chronic pain in Japan.

BACKGROUND: Chronic pain is a major health problem, and cognitive behavioral therapy (CBT) is its recommended treatment; however, efforts to develop CBT programs for chronic pain and assess their feasibility are remarkably delayed in Asia. Therefore, we conducted this pilot study to develop a basic individualized CBT for chronic pain (CBT-CP) and assessed its feasibility for use in Japan. METHODS: Our study was an open-labeled before-after trial without a control group conducted cooperatively in five Japanese tertiary care hospitals. Of 24 outpatients, 15, age 20-80, who experienced chronic pain for at least three months were eligible. They underwent an eight-session CBT-CP consisting of relaxation via a breathing method and progressive muscle relaxation, behavioral modification via activity pacing, and cognitive modification via cognitive reconstruction. The EuroQol five-dimensional questionnaire five level (EQ5D-5 L) assessment as the primary outcome and quality of life (QOL), pain severity, disability, catastrophizing, self-efficacy, and depressive symptoms as secondary outcomes were measured using self-administered questionnaires at baseline, post-treatment, and 3-month follow-up. Intention-to-treat analyses were conducted. RESULTS: Effect size for EQ5D-5 L score was medium from baseline to post-treatment (Hedge's g = - 0.72, 90% confidence interval = - 1.38 to - 0.05) and up to the 3-month follow-up (g = - 0.60, CI = - 1.22 to 0.02). Effect sizes for mental and role/social QOL, disability, catastrophizing, self-efficacy, and depressive symptoms were medium to large, although those for pain severity and physical QOL were small. The dropout rate was acceptably low at 14%. No severe adverse events occurred. CONCLUSION: The findings suggest that CBT-CP warrants a randomized controlled trial in Japan. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000020880. Registered on 04 February 2016.

Association between neuropathic pain characteristics and DNA methylation of transient receptor potential ankyrin 1 in human peripheral blood.

Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1 (TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG islands in the TRPA1 gene were examined using whole blood. Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 in these patients also significantly increased together with increase in DN4 scores. Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.

Continuous Mandibular Nerve Block for Intractable Mandibular Pain Due to Antiresorptive Agent-Related Osteonecrosis of the Jaw: A Case Report.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) causes severe pain that cannot be controlled well by common analgesic drugs. This is a first case report of intractable mandibular pain due to ARONJ that was eliminated by a continuous mandibular nerve block. A 72-year-old woman with osteoporosis had been administered bisphosphonate. One year after extraction of her tooth, she was diagnosed as having ARONJ. Jaw pain was so severe that she was unable to open her mouth and eat. We performed a continuous mandibular nerve block through an indwelling catheter with levobupivacaine for pain management. After the procedure, her rest pain was markedly improved, and the pain induced by opening her mouth disappeared. We conclude that a continuous mandibular nerve block may be helpful in the management of ARONJ.

Neuropathic Characteristics In Patients With Persistent Idiopathic Facial Pain.

BACKGROUND: Persistent idiopathic facial pain (PIFP) is a subtype of painful cranial neuropathies and other facial pains. The involvement of neuropathic mechanisms in PIFP, however, remains controversial. Using the Douleur Neuropathique 4 (DN4) questionnaire, the present study examined neuropathic characteristics in patients with PIFP. METHODS: The multi-institutional retrospective study collected the following clinical data from 205 consecutive patients with adult chronic pain: gender, age, BMI, diseases causing chronic pain, disease duration, visual analogue scale score of pain strength, and DN4 score. To compare neuropathic characteristics between PIFP and postherpetic neuralgia (PHN), we selected patients with PIFP (n=19) and patients with PHN (n=33), and performing a case-control study in which each patient with PHN or PIFP was matched by age and gender (n=16 in each group). RESULTS: DN4 score was significantly lower in the PIFP group than in the PHN group before and after matching. The incidence when DN4 was ≥4 was 10.5% before matching and 12.5% after matching in the PIFP group, both of which were significantly lower than those in the PHN group before and after matching (66.7% and 75.0%). CONCLUSION: Ten percent of the PIFP patients likely show neuropathic pain characteristics.

Resting-state brain functional connectivity in patients with chronic pain who responded to subanesthetic-dose ketamine.

Ketamine has been used to treat chronic pain; however, it is still unknown as to what types of chronic pain is ketamine effective against. To identify the effect of administration of subanesthetic-dose ketamine in patients with chronic pain and to clarify the mechanism of the effect, we retrospectively investigated brain functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). Patients were divided into responders (Group R: ≥50% improvement on Numerical Rating Scale) and non-responders (Group NR). We compared the differences in terms of brain functional connectivity by seed-to-voxel correlation analysis. Two-sample t-test revealed significant lower connectivity between the medial prefrontal cortex (mPFC) and precuneus in Group R. We also found a significant negative correlation between the improvement rate and functional connectivity strength between the mPFC and precuneus. These findings suggest that subanesthetic-dose ketamine is effective in patients with chronic pain whose brain functional connectivity between the mPFC and precuneus is low. We believe that the current study explored for the first time the correlation between brain functional connectivity and the effect of subanesthetic-dose ketamine for chronic pain and indicated the possibility of use of the predictive marker in pharmacological treatment of chronic pain.

Constant Current vs. Constant Voltage Systems for Temporal Spinal Cord Stimulation for Intractable Pain.

Although spinal cord stimulation (SCS) is a useful treatment for chronic intractable pain, the optimal method of stimulation has not yet been established. In this prospective, crossover study, we compared the efficacy of using a constant current (CC) system with that of a constant voltage (CV) system for temporal SCS. Twenty patients were enrolled and divided into two groups. For 10 patients, a CV system was applied on Days 1-5, followed by the use of a CC system on Days 6-10. For the other 10 patients, a CC system was applied for the first five days, followed by a CV system for the subsequent five days. We evaluated the alteration of pain intensity using a visual analogue scale (VAS), the area of stimulation, the stability of effect, and patient satisfaction regarding treatment. The pain scores decreased significantly after the start of the SCS. There was no significant difference in the change in VAS between the two systems. The stimulation method used for temporal SCS did not affect the reduction of pain intensity. Patients felt a wider stimulation area by the CC system compared to the CV system.

Injustice Experience Questionnaire, Japanese Version: Cross-Cultural Factor-Structure Comparison and Demographics Associated with Perceived Injustice.

OBJECTIVE: The Injustice Experience Questionnaire (IEQ) assesses injury-related perceived injustice. This study aimed to (1) develop a Japanese version (IEQ-J), (2) examine its factor structure, validity, and reliability, and (3) discover which demographic variable(s) positively contributed to prediction of IEQ-J scores. METHODS: Data from 71 patients (33 male, 38 female; age = 20+) with injury pain were employed to investigate factor structure by exploratory and confirmatory factor analyses. Concurrent validity was examined by Pearson correlation coefficients among the IEQ-J, Brief Pain Inventory (BPI), and Pain Catastrophizing Scale (PCS). Internal consistency was investigated by Cronbach's alpha, and test-retest reliability was indicated with intra-class correlations (ICCs) in 42 of 71 patients within four weeks. Relations between demographic variables and IEQ-J scores were examined by covariance analysis and linear regression models. RESULTS: IEQ-J factor structure differed from the original two-factor model. A three-factor model with Severity/irreparability, Blame/unfairness, and Perceived lack of empathy was extracted. The three-factor model showed goodness-of-fit with the data and sufficient reliability (Cronbach's alpha of 0.90 for total IEQ-J; ICCs = 0.96). Pearson correlation coefficients among IEQ-J, BPI, and PCS ranged from 0.38 to 0.73. Pain duration over a year (regression coefficient, 11.92, 95%CI; 5.95-17.89) and liability for injury on another (regression coefficient, 12.17, 95%CI; 6.38-17.96) predicted IEQ-J total scores. CONCLUSIONS: This study evidenced the IEQ-J's sound psychometric properties. The three-factor model was the latter distinctive in the Japanese version. Pain duration over a year and injury liability by another statistically significantly increased IEQ-J scores.

Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as Treatment of Painful Muscle Cramps in Patients with Lumbar Spinal Stenosis and Its Minimum Effective Dose.

Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) is a Kampo medicine, which is known to be effective against muscle cramps as well as crampy pain in the gastrointestinal smooth muscle and skeletal muscle. However, glycyrrhizin in this medicine also causes adverse drug reactions such as hypokalemia, hypertension, and edema. We analyzed the therapeutic efficacy of Shakuyaku-kanzo-to for painful muscle cramps associated with lumbar spinal stenosis and clarified its minimum effective dose. 58 patients with lumbar spinal stenosis and painful muscle cramps were included. We evaluated the therapeutic efficacy of Shakuyaku-kanzo-to (n=16) comparing with eperisone hydrochloride (n=14). We then examined the minimum effective dose of Shakuyaku-kanzo-to in the remaining 28 patients. Shakuyaku-kanzo-to reduced the frequency of painful muscle cramps to less than 50% in 13 of 16 patients. However, eperisone hydrochloride reduced it to the same level in 4 of 14 patients. The onset of the maximum therapeutic effect of Shakuyaku-kanzo-to was less than 3 days from the start of treatment in 11 of 15 patients. Regarding the minimum effective dose for painful muscle cramps, 2.5 g of Shakuyaku-kanzo-to used as needed had a therapeutic effect that was equivalent to the regular use of 7.5 g/day (given in divided doses three times daily). Our data show that Shakuyaku-kanzo-to is effective for painful muscle cramps associated with lumbar spinal stenosis. The dosage of 2.5 g of Shakuyaku-kanzo-to as needed had a therapeutic effect that was equal to the regular use of 7.5 g/day.

The efficacy of fluorocarbon, surfactant, and their combination for improving acute lung injury induced by intratracheal acidified infant formula.

We conducted the current study to compare the efficacy of partial liquid ventilation (PLV), pulmonary surfactant (PSF), and their combination in ameliorating the acidified infant-formula-induced acute lung injury (ALI). In the Part I study, 42 rabbits receiving volume-controlled ventilation with positive end-expiratory pressure 10 cm H(2)O were randomly divided into 6 groups (groups noninjuryI, gas ventilation [GVi], PLVi, PSFi, PLVi-->PSFi, and PSFi-->PLVi). ALI was induced by intratracheal acidified infant formula (2 mL/kg, pH 1.8). Group GVi received neither PLV nor PSF therapy. Groups PLV and PSF received intratracheal fluorocarbon 15 mL/kg or surfactant 100 mg/kg, respectively, 30 min after acidified infant formula. Groups PLVi-->PSFi and PSFi-->PLVi received both treatments at 30-min intervals. In Part II, 42 rabbits (in 6 groups) undergoing pressure-controlled ventilation received the same drug therapies as in Part I. The lungs were excised to assess biochemical and histological damage 150 min after induction of ALI. In Parts I and II, PSF, fluorocarbon, and their combination attenuated lung leukosequestration and edema and superoxide production of neutrophils, consequently improving oxygenation, lung mechanics, and pathological changes. Independent of ventilation mode, PSF followed by fluorocarbon provided the most beneficial effects and fluorocarbon followed by PSF produced the least efficacy.

Attenuation of acute lung injury with propofol in endotoxemia.

Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory and immune responses. Propofol is an antiinflammatory and immunosuppressive drug. We conducted this study to evaluate whether propofol attenuates ALI associated with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3 groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a bolus followed by continuous infusion at 4 or 15 mg x kg(-1) x h(-1)) was started 15 min before endotoxin. The other ALI group received soybean-oil emulsion. The nonlung injury control group received infusion of both vehicles. The lungs were mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did not differ among groups. The large dose of propofol attenuated lung leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio), and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar lavage fluid) and resulted in better oxygenation, lung mechanics, and histological change. The small dose of propofol failed to do so. Our findings suggest that a large dose of propofol successfully mitigates physiological, biochemical, and histological deterioration in ALI in endotoxemia.

Intratracheal application of recombinant surfactant protein-C surfactant to rabbits attenuates acute lung injury induced by intratracheal acidified infant formula.

UNLABELLED: Our aim in the current study was to determine whether recombinant surfactant protein-C (rSP-C) surfactant improves acute lung injury (ALI) induced by intratracheal acidified milk products. Twenty-eight rabbits were randomly divided into four groups. ALI was induced with intratracheal acidified infant formula (0.8 mL/kg, pH 1.8) in 3 groups. The control group received intratracheal acidified saline. Therapy groups received 1 of 2 doses of intratracheal rSP-C surfactant (0.5 or 2 SP-C mg/kg) 30 min after the acidified infant formula. The lungs were ventilated with 100% oxygen for 4 h after induction of ALI. Acidified infant formula dramatically reduced oxygenation and lung compliance, and increased resistance. Both doses of rSP-C improved the variables [mean PaO(2) (mm Hg) and compliance (mL/cm H(2)O) at 4 h: 61 and 0.4 for infant formula, 162 and 1.0 for small-dose rSP-C, and 152 and 1.2 for large-dose rSP-C, respectively; P < 0.05]. Pulmonary leukosequestration and edema, and severe morphological changes were attenuated by rSP-C treatment (ALI score: 14, 7, 7 in infant formula, small-dose rSP-C, and large-dose rSP-C; P < 0.05). The efficacy was similar for the two doses of rSP-C. These findings suggest that intratracheal administration of rSP-C ameliorates ALI induced by aspiration of acidified milk products. IMPLICATIONS: Small or large doses of recombinant surfactant protein-C surfactant given 30 min after intratracheal acidified infant formula attenuated physiological, biochemical, and morphological lung damage.

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: determination of optimal dose and positive end-expiratory pressure level.

OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used for acute lung injury induced by oleic acid or lung lavage. Positive end-expiratory pressure (PEEP) during partial liquid ventilation enhances the efficacy of fluorocarbon. The aim of the current study was to assess whether partial liquid ventilation can repair lung damage induced by intratracheal acidified infant formula and to determine the optimal fluorocarbon dose and PEEP level. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits. INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal acidified infant formula in four groups. Next, three groups received 10, 15, or 20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated. For study 2, acute lung injury was induced in five groups. One group was gas ventilated at a PEEP of 5 cm H2O, whereas the other four groups received fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10, or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of 15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide production of neutrophils, resulting in similar improvements in oxygenation, lung mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality from pneumothorax. In study 2, the combination of PEEP with partial liquid ventilation improved gas exchange, lung compliance, pulmonary edema, and histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and PEEP improved the physiologic, biochemical, and histologic lung injury induced by acidified infant formula. The beneficial effects of partial liquid ventilation are due, in part, to inhibition of pulmonary neutrophil accumulation and activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our model were 15 mL/kg and 10 cm H2O, respectively.

ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits.

UNLABELLED: Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) expressed in the lung is thought to play a crucial role in the pathogenesis of endotoxin-induced acute lung injury (ALI). In this two-part study, we determined whether ONO-1714, a new selective iNOS inhibitor, attenuates endotoxin-induced ALI in rabbits. For Part I of the study, a control group received IV saline and ALI was induced by IV infusion of endotoxin 5 mg/kg over 30 min in 4 groups. Three groups received either 0.1, 0.03, or 0.01 mg/kg of ONO-1714 10 min before the start of endotoxin and the fourth group received saline. For Part II of the study, ALI was induced by endotoxin infusion in all 6 groups. One group was treated with saline. The other 5 groups received ONO-1714 0.1 mg/kg at various timings (10 min before or 1, 2, 3, or 4 h after ALI induction). The lungs were mechanically ventilated with 40% oxygen for 6 h after induction of ALI. In Part I, pretreatment with 0.1 mg/kg ONO-1714 mitigated endotoxin-induced ALI. In Part II, early posttreatment (within 2 h after the insult) with ONO-1714 was as effective as pretreatment in improving oxygenation, lung mechanics, lung leukosequestration, pulmonary edema, and histological change. However, lung damage was not improved in rabbits receiving the drug 3 or 4 h after endotoxin. These data suggest that the current study is a basis for future clinical trials to elucidate whether ONO-1714 can be a promising therapeutic approach in patients with acute respiratory distress syndrome induced by endotoxin/sepsis. IMPLICATIONS: An excess of nitric oxide is thought to play a crucial role in the pathogenesis of acute organ injury in endotoxemia. Early posttreatment with ONO-1714, a nitric oxide synthase inhibitor, attenuated physiological, biochemical, and pathological changes in endotoxin-induced acute lung injury in rabbits.

The efficacy of lafutidine in improving preoperative gastric fluid property: a comparison with ranitidine and rabeprazole.

IMPLICATIONS: Acid aspiration syndrome remains a potentially critical perioperative complication. We compared lafutidine, ranitidine, and rabeprazole for reduction of preoperative gastric fluid acidity and volume in elective surgery and found that these variables were minimized with a single morning dose of lafutidine 20 mg compared with ranitidine or rabeprazole. Preoperative oral lafutidine may be an alternative to ranitidine as a prophylaxis against aspiration pneumonia.