The increased analgesic efficacy of cold therapy after an unsuccessful analgesic experience is associated with inferior parietal lobule activation.

Prior experiences of successful and failed treatments are known to influence the efficacy of a newly applied treatment. However, whether that carry-over effect applies to non-pharmacological treatments is unknown. This study investigated how a failed treatment history with placebo analgesic cream affected the therapeutic outcomes of cold-pack treatment. The neural correlates underlying those effects were also explored using functional magnetic resonance imaging. The effect of the placebo analgesic cream was induced using placebo conditioning with small (44.5 °C to 43.7 °C, negative experience) and large (44.5 °C to 40.0 °C, positive experience) thermal stimuli changes. After the placebo conditioning, brain responses and self-reported evaluations of the effect of subsequent treatment with a cold-pack were contrasted between the two groups. The negative experience group reported less pain and lower anxiety scores in the cold-pack condition than the positive experience group and exhibited significantly greater activation in the right inferior parietal lobule (IPL), which is known to be involved in pain relief. These findings suggest that an unsatisfying experience with an initial pain-relief treatment could increase the expectations for the complementary treatment outcome and improve the analgesic effect of the subsequent treatment. The IPL could be associated with this expectation-induced pain relief process.

Development of a high-dose vaccine formulation for prevention of megalocytivirus infection in rock bream (Oplegnathus fasciatus).

A formalin-inactivated red sea bream iridovirus (RSIV) vaccine was prepared using the culture supernatant of a persistently infected Pagrus major fin cell line (PI-PMF) with IVS-1 strain (RSIV subtype II Meglaocytivirus). Rock bream (Oplegnathus fasciatus) were injected with a high-dose, ultracentrifuged megalocytivirus vaccine (Ultra HSCMV, 7.0 × 1010 copies/mL), a high-dose supernatant of cultured megalocytivirus vaccine (HSCMV, 1.0 × 1010 copies/mL), a supernatant of cultured megalocytivirus vaccine (SCMV, 1.0 × 109 copies/mL), and a low-dose of cultured megalocytivirus vaccine (LSCMV, 1.0 × 108 copies/mL). The vaccine efficacies for the various vaccine formulations were determined done following injection challenge with IVS-1 (1.0 × 104 copies/0.1 mL/fish), and the four different vaccines exhibited cumulative mortalities of 10.0 ± 0.0%, 48.3 ± 7.6%, 75.0 ± 5.0%, and 100.0 ± 0.0%, respectively. Additionally, the dose-dependent vaccine efficacy was also confirmed using two different cohabitation methods that included challenges G (general) and I (individual). When squalene + aluminum hydroxide (SqAl) was used as an adjuvant for the HSCMV or SCMV vaccine, cumulative mortalities of 30.0 ± 5.0% and 48.3 ± 7.6%, respectively, were obtained; moreover, these two adjuvants exhibited the highest efficacy in this study. The observed difference in survival post-challenge for the different vaccine concentrations was not reflected in the differences in neutralizing antibody titers. It was found that the water temperature during immune induction plays a less important a role than the water temperature during the challenge test, in which lowering the water temperature from 25 °C to 21 °C during a challenge improved the level of protection from cumulative mortalities from 35% to 10%. This study demonstrated that protection against mortality using inactivated vaccines against RSIVD in rock bream, which are known to be the most susceptible species to RSIV infection, is dependent upon antigen dose and temperature during the challenge.

Optimal dose of combined rocuronium and cisatracurium during minor surgery: A randomized trial.

BACKGROUND: Combined rocuronium and cisatracurium have synergistic effects. We investigated whether reduced doses are effective during coadministration, by monitoring neuromuscular relaxation during surgery. METHODS: This randomized, controlled clinical trial was registered at http://clinicaltrials.gov (registration number NCT02495038). The participants were 81 patients scheduled for elective mastoidectomy and tympanoplasty. Participants were assigned to groups, including the intubating dose group (Group I, n = 27; combined ED95 rocuronium and ED95 cisatracurium), the small reduction group (Group S, n = 27; dose reduced by 10% of each ED95), or the large reduction group (Group L, n = 27; dose reduced by 20% of each ED95). Drugs were administered to patients and a timer was started using TOF-Watch monitoring. TOF (train-of-four) was monitored at the ulnar nerve, at a setting of 2 Hz/12 s. We recorded the time to TOF ratio = 0 (onset), time to first TOF ratio > 25% (duration 25%), and TOF 25-75% (recovery index) under total intravenous anesthesia. One-way analysis of variance was used for statistical analyses (α = 0.05, ß = 0.2). RESULTS: There were no significant demographic differences between groups. Group L had a longer duration to onset (mean ±â€Šstandard deviation, 399.3 ±â€Š147.8 seconds) and shorter duration 25% (39.4 ±â€Š6.8 minutes) compared to Group I (212.8 ±â€Š56.0 s and 51.3 ±â€Š8.47 minutes, respectively) and Group S (230.7 ±â€Š60.6 s and 47.9 ±â€Š10.7 minutes, respectively). There were no other significant differences between groups. CONCLUSION: Our findings contribute to determining clinically effective combinations of rocuronium and cisatracurium, as well as to predicting the pharmacokinetic characteristics of the synergistic effects. We suggest that reducing doses of both drugs by approximately 10% of their respective ED95 values is sufficient to maintain neuromuscular relaxation during minor surgery.

Effects of seasonal differences in testosterone and cortisol levels on pain responses under resting and anxiety conditions.

PURPOSE: This study investigated whether hormones and pain perception are associated with exam anxiety, and also whether exam anxiety is affected by seasonal differences in testosterone and cortisol levels. MATERIALS AND METHODS: Forty-six healthy males were recruited from a medical college. Anxiety was induced by having participants perform the Objective Structured Clinical Examination. Pressure was applied to the participants to induce pain. Pain thresholds, pain ratings, anxiety ratings, blood pressure, heart rate, salivary testosterone and cortisol levels were measured under resting and anxiety conditions in the spring and summer. Data were collected from 46 participants during the spring (n=25) and summer (n=21). RESULTS: Pain thresholds and testosterone levels were significantly lower under anxiety than at rest for all participants (n=46), while cortisol levels, pain ratings, and anxiety ratings were significantly higher under anxiety than at rest. In the spring (n=25), testosterone levels were significantly higher at rest than under anxiety, while there was no difference in cortisol levels between resting and anxiety conditions. In the summer (n=21), cortisol levels were significantly higher under anxiety than at rest, while there was no difference in testosterone levels between resting and anxiety conditions. There were no significant seasonal differences in pain and anxiety ratings and pain threshold. CONCLUSION: These results indicate that seasonal differences in testosterone and cortisol levels under anxiety and at rest may affect pain responses. These results also suggest that acute clinical pain may be relieved by managing anxiety that is related to a decrease of testosterone in spring and a large increase of cortisol in summer.

Changes in pain perception and hormones pre- and post-kumdo competition.

The psychological stress of competition is a powerful stimulus affecting numerous hormones, which in turn change how pain is perceived. This study investigated whether a kumdo (kendo) team competition may be related to changes in hormones and pain. Seventeen healthy male kumdo practitioners participated in this experiment. Pain experiments were conducted by applying noxious stimuli with a thermal stimulator 10 min before a kumdo competition and 30 min post-competition. Serum testosterone, cortisol, beta-endorphin levels, pain thresholds, pain ratings at 48 °C and during blood sampling (sampling pain), anxiety, blood pressure, and heart rate were measured pre- and post-competition. Anxiety, pain threshold, testosterone/cortisol ratio, and blood pressure were significantly higher pre-competition compared to post-competition, while cortisol and pain ratings were significantly lower pre-competition than post-competition. There were significant correlations between the number of previous competitions and testosterone levels both pre-competition and post-competition. In pre-competition measurements, sampling pain increased with an increase in systolic blood pressure, heart rate, and beta-endorphins, and a decrease in age. In post-competition measurements, sampling pain increased with an increase in diastolic blood pressure and a decrease in testosterone levels. These results indicate that severe psychological pre-competition stress was associated with reduced pain ratings, perhaps in order to improve athletic performance. This also suggests that competitors may be at risk of potential injury due to changes in pain perception, and careful consideration should be taken to avoid potential injury before and during competition.

Ankle-brachial blood pressure differences in the beach-chair position of the shoulder surgery.

BACKGROUND: During shoulder surgery, blood pressure is frequently measured at the ankle. Anesthetic complications may result when ankle blood pressure is higher than brachial blood pressure and anesthesiologists misinterpret ankle blood pressure as brachial blood pressure. Therefore, we investigated whether ankle blood pressure is significantly higher than brachial blood pressure before anesthesia induction, during induction, after tracheal intubation, before beach chair position, and in the beach chair position. METHODS: Thirty patients requiring general anesthesia for shoulder surgery were included in this study. Ankle and brachial blood pressure were simultaneously measured before induction, during induction, after intubation, before beach chair position, and in the beach chair position. RESULTS: Ankle blood pressure was higher than brachial blood pressure before induction, during induction, after intubation, before beach chair position, and in the beach chair position. Ankle-brachial blood pressure differences in the beach chair condition were much higher than in four other conditions. The correlation coefficient between mean ankle-brachial blood pressure differences before the beach chair position and mean ankle-brachial blood pressure differences in the beach chair position was 0.616. Brachial systolic blood pressure could be predicted by regression equations (R(2) = 0.306-0.771). CONCLUSIONS: These results suggest that anesthesiologists should consider these ankle-brachial blood pressure differences when monitoring anesthesia in the beach chair position.

Placebo effects on analgesia related to testosterone and premotor activation.

Using functional magnetic resonance imaging, we tested whether graded placebo conditions could modulate the degree of placebo effect and brain activation patterns in study participants and whether the placebo effect could be influenced by hormones. Each participant was investigated under three conditions: the control (no placebo) condition, the low-placebo condition, and the high-placebo condition (HPC). Activations of the premotor areas, anterior cingulate cortex, and prefrontal cortex were stronger in the HPC compared with those in the control and low placebo conditions. The premotor areas were activated by increased testosterone levels under the HPC. These results suggest that testosterone may affect the brain activation and response to pain during a high-placebo response, with the data supported by brain imaging.

Aging impairs vasodilatory responses in rats.

BACKGROUND: Aging causes profound changes of stiffness and compliance in the cardiovascular system, which contributes to decreased cardiovascular reserve. Mechanisms of the underlying endothelial vasodilator dysfunction in vasodilator signaling pathways may occur at multiple sites within any of these pathways. METHODS: Age-related changes in the vasculature were investigated in adult young (3-6 months, Y) and old (26-29 month, O) Wistar rats (n = 6). The aortas were carefully dissected from the rat and cut into rings 1.5-2.0 mm in length to measure in vitro isometric tension. Vasorelaxant responses of aortic rings to acetylcholine (ACh), sodium nitroprusside (SNP) and P1075 were examined using Dose Response software (AD Instruments, Mountain View, CA). RESULTS: Endothelium-dependent vasodilator function was impaired. The endothelium of aging rats impaired endothelial NO dependent vasodilation, but the machinery for vasodilation was not impaired. CONCLUSIONS: Age-related NO-mediated vasorelaxation in the aging endothelium was inhibited and appears to be major mechanism of vascular change and impaired vascular regulation.

Dilutional hyponatremia developed during hysteroscopic myomectomy: A case report.

Hysteroscopy is a procedure that may appear minimally invasive, but may result in potentially disastrous complications. A hysteroscopy requires the insertion of a hysteroscope into the uterine cavity and the installation of a suitable distention medium for the visualization of the endometrium. Fluid overload due to the absorption of distention media during hysteroscopy can cause mild to severe complications, including hyponatremia, hypoosmolarity, nausea, vomiting, headache, arrhythmia, blindness, confusion, seizure, cerebral edema, brain herniation, and death. We report a case of a 41 year-old female patient who underwent elective hysteroscopic myomectomy under general anesthesia. Approximately 4 hours after the beginning of the surgery, the patient's serum sodium concentration dropped to 109 mM. She was treated with furosemide and recovered without sequelae.

Different brain activation patterns to pain and pain-related unpleasantness during the menstrual cycle.

BACKGROUND: The changes in the functional magnetic resonance imaging signal during anticipation, pain stimulation, and the poststimulation periods were investigated to determine whether changes in sex hormones affect brain activity. METHODS: Eighteen participants were examined twice, once in the follicular phase and once in the luteal phase. Half the participants were tested first during the follicular phase, and the other half were tested first in the luteal phase. RESULTS: The pain and unpleasantness ratings were significantly higher in the luteal phase than in the follicular. During the anticipation of pain, the prefrontal cortices were activated during the follicular phase, whereas the parahippocampal gyrus and amygdala were activated during the luteal phase. During the pain stimulation, putamen and cerebellum and precentral gyrus involving motor preparation and defense mechanism related to antinociceptive behavior were activated during the follicular phase, whereas the thalamus was activated during the luteal phase. During the poststimulation periods, the prefrontal cortices were activated during the follicular phase, whereas parahippocampal gyrus was activated during the luteal phase. The temporal pole was activated during the anticipation, pain stimulation, and poststimulation periods of the luteal phase. CONCLUSIONS: During surgical and medical procedures, requirements of anesthetic and analgesic and anxiolytic drugs may be reduced during the follicular phase and increased during the luteal phase. These results highlight the need to consider the effects of the sex hormones in women when designing clinical or neuroimaging studies or when treating patients for pain and pain-related unpleasantness.

The effect of pretreatment with thiopental on reducing pain induced by rocuronium injection.

We examined whether pretreatment with a small dose of thiopental was effective in reducing pain induced by the intravenous injection of rocuronium. Withdrawal movement was used to assess pain reduction. Ninety patients were randomly assigned to one of two groups: patients in the control group were pretreated with 2 mL saline, and those in the thiopental group were pretreated with 2 mL (50 mg) thiopental. Thiopental 5 mg/kg was injected intravenously. After a loss of consciousness, the upper arm was compressed with a rubber tourniquet, and the pretreatment drugs were administered. Thirty seconds later the tourniquet was removed and 0.6 mg/kg rocuronium was administered. Withdrawal movement was assessed using a four-grade scale: no movement, movement limited to the wrist, to the elbow or to the shoulder. The frequency of withdrawal movement in the group pretreated with thiopental was lower than in the control group (34 vs. 13, p < 0.05). We concluded that pretreatment with 2 mL (50 mg) thiopental is effective in reducing pain caused by the intravenous injection of rocuronium.

Intravenous magnesium sulfate administration reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia: part I: comparing propofol requirements according to hemodynamic responses: part II: comparing bispectral index in control and magnesium groups.

BACKGROUND: The authors investigated whether an intravenous administration of magnesium sulfate reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia. METHODS: Part I study: 54 patients undergoing total abdominal hysterectomy were randomly divided into two groups (n = 27 per group). The patients in the control group received 0.9% sodium chloride solution, whereas the patients in the magnesium group received magnesium (50 mg/kg as a bolus, then 8 mg x kg(-1) x h(-1)). To maintain mean arterial blood pressure (MAP) and heart rate (HR) at baseline value, the propofol infusion rate was changed when the MAP or the HR changed. The amount of propofol infused excluding the bolus dosage was divided by patient's body weight and total infusion time. Part II study: Another 20 patients were randomly divided into two groups (n = 10 per group). When the MAP and HR had been maintained at baseline value and the propofol infusion rate had been maintained at 80 microg x kg(-1) x min(-1) (magnesium group) and 160 microg x kg(-1) x min(-1) (control group), bispectral index (BIS) values were measured. RESULTS: Part I: The mean propofol infusion rate in the magnesium group (81.81 +/- 13.09 microg x kg(-1) x min(-1)) was significantly less than in the control group (167.57 +/- 47.27). Part II: BIS values in the control group (40.70 +/- 3.89) were significantly less than those in the magnesium group (57.80 +/- 7.32). CONCLUSION: Intravenous administration of magnesium sulfate reduces propofol infusion requirements. These results suggest that magnesium administration may have an effect on anesthesia or analgesia and may be a useful adjunct to propofol anesthesia.