Perioperative Nerve Blockade Reduces Acute Postoperative Pain after Orthognathic Surgery.

Background: The role of perioperative pain management is not only to reduce acute postoperative pain (POP) but also to prevent chronic POP. It would be important to know the usefulness of nerve blockade for perioperative management. However, it has not been extensively studied in orofacial surgery. The objective of the study was to investigate whether perioperative nerve blockade reduces acute POP after orthognathic surgery. Methods: Patients scheduled for orthognathic surgery were retrospectively reviewed ("preblock group": the nerve blockade was performed before emergence from general anesthesia, and "no preblock group": the nerve blockade was not performed before emergence from general anesthesia). The visual analog scale (VAS; 0-100 mm)-POP intensity, the VAS-POP areas under the curves (VASAUCs (mm × day)) in addition to VASAUCs for postoperative hours 6 (VASAUC_6), 12 (VASAUC_12), 18 (VASAUC_18), and 24 (VASAUC_24), the analgesic requirement period (day), and the number of days with pain (day) were analyzed. Data are presented as median (interquartile range) values. Results: Fifty-six patients (preblock group, 22; no preblock group, 34) were included (21 males, 35 females; age: 22.0 [21.0-28.0] years). VASAUC_6, VASAUC_12, VASAUC_18, and VASAUC_24 in the preblock group were significantly smaller than those in the no preblock group (3.5 [2.0-7.2] vs. 7.4 [5.1-10.0], p = 0.0007; 9.5 [6.4-13.7] vs. 15.0 [7.2-22.9], p = 0.042; 15.7 [10.3-23.1] vs. 29.3 [18.9-37.2], p = 0.0002; and 17.6 [12.7-27.2] vs. 39.5 [22.9-46.9], p = 0.001, respectively). There were no significant differences between the 2 groups in VASAUC, the analgesic requirement period, and the number of days with pain (p > 0.05). Conclusions: Perioperative nerve blockade reduces POP after orthognathic surgery, especially for the acute postoperative period.

Leuconostoc mesenteroides subsp. strain NTM048 ameliorated nasal symptoms in patients with Japan cedar pollinosis: Randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Lactobacillales including L mesenteroides have beneficial effects on human health, including improvement of psychological status and alleviation of allergic rhinitis. In mice, L mesenteroides subsp. strain NTM048 (NTM048) increased intestinal s-IgA. In humans, however, the effects of NTM048 on s-IgA secretion have been unclear. STUDY: This 16-week trial was performed using a double-blind, placebo-controlled, parallel group design. We aimed to establish whether Leuconostoc mesenteroides subsp. strain NTM048 increases the secretion of s-IgA in saliva. Forty healthy adults and forty patients with Japanese cedar pollinosis were recruited. Participants took either 2 test capsules including NTM048 (1010 CFU/day), or 2 placebo capsules per day, for 16 weeks. They were asked to collect their saliva and answered POMS2, a questionnaire about psychological status. The patients also answered questions about nasal symptoms. Blood samples were collected from the patients with Japanese Cedar pollinosis. Stool samples were collected at the start and on the last day of the trial. RESULTS: All subjects completed the trial. It was conducted during the season when Japanese cedar pollen is most scattered. Serum concentration of Japanese cedar pollen-specific IgE was > 2.0 UA/mL in patients with Japanese cedar pollinosis. The amount of s-IgA in saliva was not increased by NTM048 in overall subjects, and Japanese cedar pollen-specific IgE was not changed by NTM048 in patients with Japanese cedar pollinosis. The symptom of nasal blockage was improved by NTM048 12 weeks after the start of trial. post hoc analysis indicated a positive correlation between improving psychological status and the increase in occupation ratio of lactobacillus including NTM048. CONCLUSION: The amount of s-IgA in saliva was not increased by NTM048, but nasal blockage was improved by it. Psychological status might be improved if dosage of NTM048 is raised to the degree that NTM048 might be increased in the intestinal tract.

Preoperatively assessed offset analgesia predicts acute postoperative pain following orthognathic surgery.

OBJECTIVES: High intensity and longer duration of acute postoperative pain are generally associated with a higher risk of developing chronic postoperative pain. Therefore, it is important to identify the preoperative predictors for acute postoperative pain. Preoperative evaluation of offset analgesia (OA) and the Pain Catastrophising Scale (PCS) may be potential predictors for acute postoperative pain. This study aimed to investigate the relationship between preoperative OA, PCS, and acute postoperative pain following orthognathic surgery. METHODS: Thirty patients (19 females) scheduled to undergo orthognathic surgery were included in this study. OA and PCS were evaluated preoperatively, and the patients reported their postoperative pain intensity using the visual analogue scale [0-100 mm] until it reached zero (number of days with pain). OA was induced on the dominant forearm via three consecutive painful heat pulses delivered for 5 s (T1=46 °C), 5 s (T2=47 °C), and 20 s (T3=46 °C). Subsequently, the associations between OA, PCS, and the number of days with pain were analysed. RESULTS: The median duration of postoperative pain was 10.3 days. Multiple linear regression analysis showed a significant (p=0.0019) predictive value of OA (p=0.008) for the number of days with pain. The PCS-magnification component was positively correlated with the number of days with pain (R=0.369, p=0.045), with no predictive values of PCS-total and PCS-subscale scores observed. CONCLUSIONS: Preoperative evaluation of OA may be a new individualised, predictive tool for the number of days with acute postoperative pain following orthognathic surgery; hence, a possible biomarker for the patient's vulnerability to developing chronic postoperative pain. ETHICAL COMMITTEE NUMBER: The study was approved by the Ethics Committee of Meikai University (A1624, A2113). TRIAL REGISTRY NUMBER: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) Clinical Trial (Unique ID: UMIN000026719, UMIN000046957).

Conditioned pain modulation is not associated with thermal pain illusion.

OBJECTIVES: Paradoxical sensations, known as thermal pain illusions, can be evoked by painful cold-heat pulse stimulation. They may provide diagnostic value; however, the possible interaction between conditioned pain modulation and thermal pain illusions has not been explored. The present study examined: (1) whether conditioned pain modulation could be induced by alternating tonic painful cold-heat pulse stimulation; and (2) whether the presence of thermal pain illusions during the conditioning stimulus influences the degree of conditioned pain modulation. METHODS: This study was approved by the Ethics Committee of Meikai University (A1507). Conditioned pain modulation was provoked using alternating painful cold-heat pulses delivered at 20-s intervals applied to the forearm. Thermal pain illusions were qualitatively evaluated, and conditioned pain modulation was assessed quantitatively using the pressure pain threshold as a test stimulus. Differences in the conditioned pain modulation effect between the participants who experienced thermal pain illusions and those who did not were analysed using Student's t-test. RESULTS: A significant positive conditioned pain modulation effect (51.0 ± 4.7%, overall effect) was detected. There was no significant difference in conditioned pain modulation between the participants who experienced thermal pain illusions and those who did not (44.3 ± 6.0% and 55.5 ± 6.8%, respectively; p = 0.255). CONCLUSIONS: Conditioned pain modulation induced by alternating painful conditioning cold-heat pulse stimulation was identical during the conditioning stimulation in volunteers with and without thermal pain illusions. Conditioning cold-heat pulse stimulation is useful to evaluate conditioned pain modulation. Moreover, conditioned pain modulation is not influenced by the presence of thermal pain illusions, indicating partially different underlying supraspinal, neuronal networks.

Photobiomodulation enhanced endogenous pain modulation in healthy volunteers.

To examine the effects of photobiomodulation (PBM) in healthy volunteers using photonic stimulation of acupuncture points on conditioned pain modulation (CPM), temporal summation of pain (TSP), and offset analgesia (OA), which reflect some aspects of endogenous pain modulation. We included 15 men and 15 women (age, 31.5 [27.3-37.0], body mass index, 25.7 [24.4-27.1], Fitzpatrick skin typing, II: 20, III: 8, IV: 2). CPM, TSP, and OA were evaluated after a sham procedure (control session) and after acupuncture point stimulation (LI4 and LI10 on the non-dominant forearm) using linear polarized near-infrared light irradiation (LPNILI; wavelengths peaked at approximately 1000 nm, output: 1.4 W/cm2, spot diameter: 10 mm, spot size: 1.02 cm2, maximum temperature: 40.5 °C, pulse width: 1 s, frequency: 0.2 Hz) (PBM session). Differences in CPM, TSP, and OA between the two sessions were evaluated by the paired t-test and Fisher's exact test (statistical significance: p < 0.05). Values indicate median [interquartile range]. LPNILI significantly increased CPM in all participants (control session: 12.1 [-4.5-37.4], PBM session: 23.9 [8.3-44.8], p < 0.05) and women (control session: 16.7 [-3.4-36.6], PBM session: 38.7 [24.6-52.1], p < 0.05). The CPM effect increment was significantly higher in women than in men (p = 0.0253). LPNILI decreased TSP in participants with higher TSP ratios (p = 0.0219) and increased OA in participants with lower OA scores (p = 0.0021). LPNILI enhanced endogenous pain modulation in healthy volunteers, particularly in women, as evaluated using CPM. CPM, TSP, and OA evaluations are potentially useful for discriminating PBM responders from non-responders.

Methemoglobinemia Induced by Prilocaine in a Child With Noonan Syndrome.

Limited information is currently available on methemoglobinemia caused by the administration of prilocaine in children undergoing dental procedures in Japan. This case report presents the development of methemoglobinemia due to prilocaine overdose. The patient was a female aged 5 years 8 months with Noonan syndrome who also had pulmonary valve stenosis and hypertrophic cardiomyopathy. She presented with severe dental caries affecting 12 total teeth and required general anesthesia due to a lack of cooperation during dental treatment. General anesthesia was performed, during which 3% prilocaine with 0.03 IU/mL felypressin was administered intraoperatively via infiltration. Her SpO2 gradually decreased after 30 minutes, and cyanosis was observed postoperatively. Several assessments including a 12-lead electrocardiogram, an anteroposterior chest radiograph, and venous blood gas analysis were performed to identify potential causes. However, there were no indications of acute respiratory or cardiovascular abnormalities. It was noted that a total of 192 mg prilocaine was administered during the procedure, and methemoglobinemia was suspected to have developed because of overdose. Further testing revealed an elevated serum methemoglobin of 6.9%, supporting methemoglobinemia as the cause of her decreased SpO2. In dental procedures that require the use of prilocaine to treat multiple teeth, particularly for pediatric patients, it is important to carefully manage prilocaine dosing, as an overdose may lead to methemoglobinemia.

Acute postoperative pain after orthognathic surgery can be predicted by the preoperative evaluation of conditioned pain modulation and pain catastrophizing.

INTRODUCTION: The incidence and severity of chronic postoperative pain (POP) are major clinical challenges, and presurgical conditioned pain modulation (CPM) and pain catastrophizing scale (PCS) assessments have exhibited predictive values for POP. However, whether CPM and PCS assessments are also predictive of acute POP is unknown. OBJECTIVES: We aimed to investigate the relationship between preoperative CPM and PCS and acute POP severity after orthognathic surgery by assessing preoperative CPM and PCS in 43 patients. METHODS: The pressure pain threshold and tonic painful cold-heat pulse stimulation (applied with a pain intensity score of 70 on a visual analogue scale [VAS 0-100]) were used as the test and conditioning stimuli, respectively. The pain area under the postoperative VAS area under the curve (VASAUC) was estimated. The associations between CPM, PCS, and VASAUC were also analyzed. RESULTS: No patient experienced chronic POP after 1 month. Negative and positive CPM effects (test stimulus threshold was 0% > and 0% ≤ during conditioning stimulation, respectively) were detected in 36 and 7 patients, respectively. For patients with negative CPM effects (CPM responders), multiple regression analysis revealed a prediction formula of log (VASAUC) = (-0.02 × CPM effect) + (0.13 × PCS-magnification) + 5.10 (adjusted R 2 = 0.4578, P = 0.00002, CPM effect; P = 0.002, PCS-magnification; P = 0.0004), indicating that a weaker CPM and higher PCS scores were associated with more acute POP after surgery. CONCLUSION: CPM and PCS can predict acute POP after orthognathic surgery.

Painful cold-heat segmental pulse stimulation provokes the thermal pain illusion.

PURPOSE/AIM: The thermal grill illusion is a paradoxical pain sensation induced by simultaneous exposure to spatially separated, non-painful, cold, and warm stimuli. This study aimed to determine whether paradoxical sensations are also evoked by simultaneous exposure to painful cold-heat stimuli and whether the mechanism involves modulation by segmental and extra-segmental spatial integration. MATERIALS AND METHODS: Sensory perceptions were triggered by simultaneous application of painful cold-heat pulse stimuli using a developed bedside tool equipped with quantitative thermal stimulator devices. Four conditions were investigated: (1) one device placed on the forearm (condition 1, control); (2) two devices placed on the forearm (condition 2, ipsilateral segmental integration); (3) two devices placed on the forearm and ipsilateral thigh (condition 3, extra-segmental integration); and (4) two devices placed bilaterally on the forearms (condition 4, contralateral segmental integration). The evoked perceptions of paradoxical heat sensation and the loss of cold or heat sensation were evaluated. RESULTS: The aforementioned phenomena were experienced by 11(35.4%), 3(9.7%), 3(9.7%), and 0(0.0%) subjects for conditions 1-4, respectively. Fisher's exact test revealed significant differences (p=.001) among the four conditions. However, Bonferroni post hoc analysis revealed significant differences only between conditions 1 and 4 (p=.005). CONCLUSIONS: Simultaneous painful cold-heat pulse stimulation can induce paradoxical sensations similar to those shown for non-painful thermal (cold and heat) stimuli. They were predominantly evoked by ipsilateral integration. Paradoxical sensations have diagnostic value, and quantifying them using a simple bedside tool may be useful in the clinical setting.

Expression of ABC transporters in human hepatocyte carcinoma cells with cross-resistance to epirubicin and mitoxantrone.

BACKGROUND: In order to understand the cross-resistance between epirubicin (EPI) and mitoxantrone (MIT), EPI- and MIT-resistant cells were established and their cross-resistance was evaluated. MATERIALS AND METHODS: The degrees of growth inhibition of EPI-resistant HLE-EPI cells and MIT-resistant HLE-MIT cells by anticancer drugs were measured. The mRNA expressions of multidrug resistance protein 1 (MDR1)/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2 were also measured by quantitative real-time RT-PCR. Moreover, intracellular accumulation of EPI was investigated. RESULTS: HLE-EPI cells were resistant to EPI, MIT and docetaxel. HLE-MIT cells were resistant to EPI, MIT and SN-38. HLE-EPI cells overexpressed MDR1 and HLE-MIT cells overexpressed BCRP. The intracellular accumulation of EPI was decreased in HLE-EPI and HLE-MIT cells. CONCLUSION: The results suggest that both MDR1 and BCRP can up-regulate the efflux of EPI causing resistance to EPI in HLE-EPI and HLE-MIT cells.