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A significant number of patients develop chronic pain after surgery, but prediction of those who are at risk is currently not possible. Thus, prognostic prediction models that include bio-psycho-social and physiological factors in line with the complex nature of chronic pain would be urgently required. Here, we performed a translational study in male volunteers before and after an experimental incision injury. We determined multi-modal features ranging from pain characteristics and psychological questionnaires to blood plasma proteomics. Outcome measures included pain intensity ratings and the extent of the area of hyperalgesia to mechanical stimuli surrounding the incision, as a proxy of central sensitization. A multi-step logistic regression analysis was performed to predict outcome measures based on feature combinations using data-driven cross-validation and prognostic model development. Phenotype-based stratification resulted in the identification of low and high responders for both outcome measures. Regression analysis revealed prognostic proteomic, specific psychophysical, and psychological features. A combinatorial set of distinct features enabled us to predict outcome measures with increased accuracy compared to using single features. Remarkably, in high responders, protein network analysis suggested a protein signature characteristic of low-grade inflammation. Alongside, in silico drug repurposing highlighted potential treatment options employing antidiabetic and anti-inflammatory drugs. Taken together, we present here an integrated pipeline that harnesses bio-psycho-physiological data for prognostic prediction in a translational approach. This pipeline opens new avenues for clinical application with the goal of stratifying patients and identifying potential new targets, as well as mechanistic correlates, for postsurgical pain., Competing Interests: Declaration of Competing Interest MS received research awards and travel support by the German Pain Society (DGSS) both of which were sponsored by Astellas Pharma GmbH (Germany). MS received one-time consulting honoraria by Grunenthal GmbH (Germany). None of these funding sources influenced the content of this study, and MS declares no conflict of interest. During the past 3 yr, EPZ received financial support from Grunenthal for research activities and from Grunenthal (Germany), Medtronic and Merck/MSD for advisory board activities, lecture fees, or both. All money went to the institution EPZ is working for. None of this research support/funds was used for or influenced this manuscript, and EPZ declares no conflict of interest. The remaining authors declare that they have no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Tumor progression and chronic postsurgical pain (CPSP) in patients with breast cancer are both significantly influenced by inflammation. The associations between immunoinflammatory biomarkers and long-term survival, as well as CPSP, remain ambiguous. This study examined the predictive value of immunoinflammatory biomarkers for both long-term survival and CPSP., Methods: Data on the clinicopathological characteristics and perioperative peripheral blood immunoinflammatory biomarkers of 80 patients who underwent breast cancer surgery were retrospectively collected. Optimal cut-off values for preoperative immunoinflammatory biomarkers, including the preoperative systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and pan-immune-inflammation value (PIV), were established via receiver operating characteristic (ROC) curves. Kaplan-Meier curves and Cox regression analysis were used to evaluate the relationships between preoperative immunoinflammatory biomarkers and long-term survival. The relationships among the perioperative neutrophil count (NEU), monocyte count (MONO), lymphocyte count (LYM), platelet count (PLT), SII, SIRI, NLR, PIV, dynamic changes in peripheral blood cell counts, and CPSP were further assessed using logistic regression analysis., Results: Kaplan-Meier curves revealed a considerable prolongation of disease-free survival (DFS) and overall survival (OS) in the low preoperative SII, SIRI, NLR, and PIV groups. Multivariate Cox regression analysis revealed that only an elevated preoperative SIRI was an independent risk factor for postoperative DFS (HR=8.890, P=0.038). The incidence of CPSP was 28.75%. Univariate logistic regression analysis revealed that body mass index (BMI), postoperative NEU, MONO, SIRI, and PIV were negatively correlated with the occurrence of CPSP, whereas subsequent multivariate logistic regression analysis revealed that only BMI was independently associated with CPSP (OR=0.262, P=0.023)., Conclusion: Elevated preoperative SIRI was an independent risk factor for poor DFS in breast cancer patients after surgery. In contrast, perioperative immunoinflammatory biomarkers had limited potential for predicting CPSP in patients who underwent breast cancer surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Li, Che, Li, Min, Ai, Wu, Wang, Tan, Fu, Yang, Fang, Zheng and Yan.)

Background: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the µ-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery., Methods: This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6 weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6 weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored., Discussion: The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients., Trial Registration: Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024., Competing Interests: Declarations. Ethics approval and consent to participate: The local ethics committees (Ethikkommission Nordwest- und Zentralschweiz, Basel, Switzerland, and Kantonale Ethikkommission Zürich, Zürich, Switzerland) approved the described study protocol version 2, dated on July 24, 2024, as of October 01, 2024 (reference number 2024–01080). We will obtain consent from all trial participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate systemic levels of bupivacaine after bilateral ultrasound-guided deep parasternal intercostal plan (PIP) block in cardiac surgical patients undergoing median sternotomy., Design: Prospective, observational study SETTING: Single institution; academic university hospital PARTICIPANTS: Twenty-eight adult patients undergoing cardiac surgery with median sternotomy received a PIP block with 2.5 mg/kg bupivacaine with or without dexamethasone and dexmedetomidine., Measurements: Arterial blood samples were analyzed for total serum bupivacaine concentration at 5, 15, 30, 45, 60, 90, 120, and 150 minutes after placement of PIP. Local anesthetic volume, local anesthetic adjuncts, time to extubation, postoperative pain scores, and opioid consumption were recorded., Main Results: The mean peak bupivacaine concentration was 0.60 ± 0.62 µg/mL, and the mean time to maximum concentration (Tmax) was 16.92 ± 12.97 minutes. Two patients (7.1%) had a concentration >2.0 µg/mL within 15 minutes of block placement. The mean Tmax of bupivacaine was significantly greater in patients who did not receive additives compared to those patients who did (22.86 ± 14.77 minutes v 10.0 ± 5.22 minutes; p = .004). The times to extubation and postoperative pain were not improved with additives., Conclusions: Bilateral PIP placed at the end of cardiac surgery resulted in low systemic bupivacaine levels. The inclusion of additives shortened Tmax without improving outcome., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This study evaluated the interactive effects of preoperative beta-endorphin (BE) concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol and plasma anandamide) on postoperative opioid use and pain intensity in a prospective cohort of n = 112 pregnant patients undergoing scheduled cesarean delivery. Maternal blood and CSF samples were collected preoperatively for BE and EC assays. Patients completed measures of outpatient opioid use (number of tablets used and days of use) and average pain intensity at 2 weeks postoperatively. Results of general linear model analyses controlling for maternal age, body mass index at time of delivery, and race revealed significant multiplicative interactions between EC and BE concentrations on number of opioid tablets used (based on pill count), days of opioid use, and total milligram morphine equivalents used in the 2-week follow-up period. Elevated preoperative plasma and CSF 2-arachidonoylglycerol predicted reduced outpatient opioid analgesic use, particularly for patients low in CSF BE. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (P < .02) characterized by higher preoperative BE concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma anandamide concentrations. Further exploration of interactions between EC and endogenous opioid inhibitory systems as they influence responses to opioid analgesics in other clinical pain populations may help guide the development of precision pain management approaches. PERSPECTIVE: In the postoperative setting of patients undergoing cesarean delivery, elevated ECs were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in CSF. Further exploration of interactions between these 2 inhibitory systems as they impact responses to pain management interventions appears warranted., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background/aim: There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs)., Patients and Methods: Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1β) were measured before operation and following surgery in patients with MLa. Pain levels were assessed using the Numerical Rating Scale (NRS) and Brief Pain Inventory (BPI) scale, both preoperatively and postoperatively., Results: Casp1 blood levels showed an increasing trend at postoperative day 1 (POP1) and this increase was almost significant in a linear mixed effect model (LME) analysis (p=0.06). Additionally, Casp1 blood levels were higher in patients with cancer than those with benign disease and correlated with IL-18 blood levels (r=0.24, p=0.007). Furthermore, Casp1 blood levels correlated with BPIsev (severity) score values in MLa patients (r=-0.49, p=0.048). A significant correlation was also observed between Casp1 blood levels and NRS scores in patients with MLa., Conclusion: This is the first report to evaluate two pain surveys (NRS and BPI) in MLa patients in relation to blood levels of Casp1 and eight CYTs. This analysis is important in confirming the significant correlation between NRS and BPI pain scales and Casp1 blood levels. Our study is also the first to demonstrate that adequate postoperative analgesia in patients with MLa provides better functional ability and improved patient satisfaction., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression., Objective: To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform., Study Design: We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions., Results: The median age at blood draw was 17 years (interquartile range, 15-19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal P<.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44-6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28-5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36-0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04-14.33])., Conclusion: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate-to-severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post-tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post-tonsillectomy pain., Methods: Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain., Results: Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post-tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post-tonsillectomy pain, with AUC values ranging from 0.85 to 0.95., Conclusion: This study identified novel candidate biomarker panels that effectively differentiated varying severity of post-tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries., (© 2024 John Wiley & Sons Ltd.)

Background/aim: Cysteine protease caspase-1 (Casp1) plays a crucial role in the conversion of pro-cytokines to active cytokines (CYTs). The purpose of this work was to determine Casp1 blood levels in a cohort of 114 cholecystectomy patients and assess their association with other CYTs and numeric rating scale (NRS) pain scores, postoperatively., Patients and Methods: Blood levels of Casp1 and seven CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-10, IL-1β, and IL-8) were measured at three time points; before operation, immediately after operation, and six hours after operation in 114 patients with cholelithiasis (Chole)., Results: Casp1 blood levels correlated with NRS pain scores at 24 h following surgery (p=0.016). In addition, Casp1 blood levels correlated significantly to IL-18 blood levels (p<0.001)., Conclusion: This is the first report to evaluate Casp1 blood levels in Chole patients in correlation with other CYTs. The findings confirm a significant correlation between Casp1 blood levels and NRS pain scores. Moreover, this study provides initial evidence suggesting that inhibition of the activity of Casp1 may reduce postsurgical acute phase immune response possibly through the Casp1/pro-Il-18 pathway., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: This study aimed to explore whether preoperative angiotensin II type 2 receptor (AT 2 R) level in knee osteoarthritis (OA) patients was an independent risk factor for chronic post-surgical pain (CPSP) after total knee arthroplasty (TKA)., Methods: A total of 220 patients who had undergone unilateral TKA were enrolled from October 2019 to January 2020. Quantitative sensory testing (QST), PainDETECT questionnaires (PD-Q), the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), the hospital anxiety and depression (HAD) and serum AT 2 R were collected preoperatively. The primary outcome was the incidence of CPSP, which was defined as the visual analogue scale (VAS) score ≥ 4 in the ipsilateral knee joint six months after operation., Results: The prevalence of CPSP was 13.6% (n = 30). Multiple logistic regression analysis showed that patients with higher AT 2 R level (OR: 1.007, 95% CI: 1.003-1.011) and PD-Q score (OR: 1.146, 95% CI: 1.008-1.298) before surgery had an increased risk of CPSP after surgery, and a combination of preoperative AT 2 R and PD-Q (Akaike information criterion: 147.2; area under receiver operating characteristic (ROC) curve: 0.890) was able to correctly classify 90.16% of patients into CPSP positive or negative groups., Conclusion: Our findings suggest that patients with higher preoperative AT 2 R level are at increased risk of developing CPSP following TKA. AT 2 R may serve as a candidate predictor for phenotyping CPSP in OA patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: Surgical-related inflammatory responses have negative effects on postoperative recovery. Intravenous (IV) lidocaine and dexmedetomidine inhibits the inflammatory response. We investigated whether the co-administration of lidocaine and dexmedetomidine could further alleviate inflammatory responses compared with lidocaine or dexmedetomidine alone during laparoscopic hysterectomy., Methods: A total of 160 patients were randomly allocated into four groups following laparoscopic hysterectomy: the control group (group C) received normal saline, the lidocaine group (group L) received lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion), the dexmedetomidine group (group D) received dexmedetomidine (bolus infusion of 0.5 μg/kg over 10 min, 0.4 μg/kg/h continuous infusion), and the lidocaine plus dexmedetomidine group (group LD) received a combination of lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion) and dexmedetomidine (bolus infusion of 0.5 μg/kg over 10 min, 0.4 μg/kg/h continuous infusion). The levels of plasma interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at different time points were the primary outcomes. Secondary outcomes included hemodynamic variables, postoperative visual analogue scale (VAS) scores, time to first flatus, and incidence of nausea and vomiting after surgery., Results: The levels of plasma IL-1, IL-6, and TNF-α were lower in groups D and LD than in group C and were lowest in group LD at the end of the procedure and 2 h after the operation (P < 0.05). The VAS scores were decreased in groups D and LD compared with group C (P < 0.05). The heart rate (HR) was decreased at the end of the procedure and 2 h after the operation in groups D and LD compared to groups C and L (P < 0.001). The mean blood pressure (MBP) was lower at 2 h after the operation in groups L, D, and LD than in group C (P < 0.001). There was a lower incidence of postoperative nausea and vomiting (PONV) in group LD than in group C (P < 0.05)., Conclusions: The combination of lidocaine and dexmedetomidine significantly alleviated the inflammatory responses, decreased postoperative pain, and led to fewer PONV in patients undergoing laparoscopic hysterectomy., Trial Registration: ClinicalTrials.gov ( NCT03276533 ), registered on August 23, 2017.

Opioids may influence inflammation. We compared genes associated with pain and inflammation in patients who consumed opioids (3-120 mg of oral morphine equivalents per day) with those who did not for differential expression. White blood cells were assayed in 20 patients presenting for total lower extremity joint replacement. We focused on messenger ribonucleic acid expression of complement proteins. We report that the expression of a complement inhibitor, complement 4 binding protein A, was reduced, and the expression of a complement activator, complement factor D, was increased in opioid-consuming patients. We conclude that opioid consumption may influence expression of complement activators and inhibitors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Background: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (Tmax) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy., Methods: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions., Results: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) Tmax was 24 (12) hours (confidence interval [CI], 19.5-28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (Cmax) was 0.6 (0.3) μg/mL (CI, 00.45-0.74 μg/mL) in a range of 0.3-1.2. The serum bupivacaine concentration was undetectable (<0.2 μg/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity., Conclusions: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 μg/mL) during the 96-hour study period.

Background: No consensus has yet been reached regarding the best anesthetic technique for inguinal hernia repair. This study aimed to compare postoperative clinical outcomes and inflammatory markers among patients who were anesthetized using local, spinal, or general anesthesia for inguinal hernia repair., Methods: This randomized controlled trial included patients scheduled to undergo elective unilateral inguinal hernioplasty at Siriraj Hospital during November 2014 to September 2015 study period. Patients were randomly assigned to the local (LA), spinal (SA), or general (GA) anesthesia groups. Primary outcomes were postoperative pain at rest and on mobilization at 8 and 24 hours after surgery., Results: Fifty-four patients were included, with 18 patients randomly assigned to each group. Patient demographic and clinical characteristics were similar among groups. There were no significant differences among groups for postoperative pain at rest or on mobilization at 8 and 24 hours after surgery. No significant differences were observed for interleukin-1β, interleukin-6, and interleukin-10 at any time points in any groups. Patients with local anesthesia was associated with less time spent in anesthesia (p = 0.010) and surgery (p = 0.009), lower intraoperative cost (p = 0.003) and total cost in hospital (p = 0.036); however, patient satisfaction in the local anesthesia group (94/100) was statistically significantly lower than the spinal and general anesthesia groups (100/100) (p = 0.010)., Conclusions: No statistically significant difference was observed among groups for postoperative pain scores, duration of hospital stays, complications, or change in inflammatory markers. However, time spent in anesthesia and surgery, the intraoperative cost and total cost for hernia repair, and patient satisfaction were significantly lower in the local anesthesia group than in the other two groups., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We investigated the influence of pain decrease after lumbar microdiscectomy on the interferon gamma (IFN- γ ) serum level in patients with lumbar disc herniations. The study challenges the mechanism of sciatica pain and the role of IFN- γ in radicular pain development. Material and Methods . We performed clinical and immunoenzymatic assessment in a group of 27 patients with lumbar radicular pain due to disc herniations before and 3 months after surgery. Clinical status was assessed with the use of the Numeric Rating Scale (NRS), the Pain Rating Index and Pain Intensity Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN- γ were ascertained by an immunoenzymatic method., Results: We observe significant correlations between the results of the pain in the back region assessment NRS back scale after the surgery with the level of IFN- γ before the procedure ( r s = 0.528; p = 0.008) and after the procedure ( r s = 0.455; p = 0.025). These are moderate and positive correlations-the decrease in pain is correlated with the lower IFN- γ level. Additionally, there are significant correlations between the results of the PRI scale and the IFN- γ level. The PRI score before surgery correlates positively with IFN- γ after surgery ( r s = 0.462; p = 0.023), and the PRI score after surgery correlates positively with IFN before surgery ( r s = 0.529; p = 0.005) and after surgery ( r s = 0.549; p = 0.003). All correlations are moderate in severity-severe pain before surgery correlates with a higher level of IFN- γ after surgery and also higher IFN- γ before surgery. There were significant differences in the IFN- γ level before ( Z = -2.733; p = 0.006) and after ( Z = -2.391; p = 0.017) surgery in the groups of patients with and without nerve compression. In the group of patients with nerve compression, the level of IFN- γ before and after surgery was lower., Conclusions: Less pain ratio after operation correlates with the level of IFN- γ . In the group of patients without significant nerve compression confirmed by MRI scans, the level of IFN- γ before and after surgery was higher than that in the group with nerve root compression., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 Piotr Kamieniak et al.)

Background: In this study, the μ-Opioid receptor activity was assessed pre-operatively for its association with postoperative pain level and second analgesic requirement in patients undergoing septoplasty., Methods: In our prospective study, 120 adult patients underwent septoplasty from June 2015 to January 2019 were randomly divided into 2 pre-operative groups. The first group (n = 60) was patients given tramadol (1-2 mg/kg) for post-operative analgesia, and the second group (control group) (n = 60) was initially prescribed only fentanyl (1 μg/ kg-i.v.) in the induction. Acetaminophen with codeine analgesic 325/30 mg (p.o.) was used as an rescue painkiller in the post-operative period. The μ-Opioid receptor activity was investigated in pre-operative blood samples and compared to post-operative pain level and time required for second round of analgesic administration. The visual analogue score (VAS) was used to evaluate the post-operative pain degree (0 no pain; 10 worst pain). The patients' post-operative VAS scores were evaluated upon arrival to recovery room, and at the 1st, 3rd, 7th, 10th, and 24th hour post-operative period., Results: Demographic data and peri-operative variables were similar in both study group (p < 0.05).There was no significant difference between the receptor levels in both groups and the mean receptor level was 200.94 ± 15.34 pg/mL (max:489.92 ± 22.36 pg/mL, min: 94.56 ± 11.23 pg/mL).In patients who used tramadol as the levels of μ-Opioid receptors increased, VAS scores of patients and second analgesic use decreased in post-operative period.The VAS scores in patients with higher receptor levels were lower in the recovery room (p < 0.05), 1st (p < 0.05) and 3rd hours (p < 0.05).The VAS scores were lower in the tramadol group compared to the control group (p < 0.05).Number of secondary analgesic requirement was significantly lower in patients of the tramadol group with higher receptor levels compared to the ones with lower receptor (p < 0.05) for arrival at the recovery room and 1st hour. Patients in the tramadol group needed a second pain killer much later than patients in the control group., Conclusions: Our study demonstrates that patients with higher μOR levels have a higher efficacy of opioid analgesic agents and an lesser need for additional analgesic agents., Trial Registration: This trial was registered retrospectively (The ACTRN: ACTRN12619001652167 , registration date: 26/11/2019).

BACKGROUND This study assessed the additional benefits of bupivacaine when combined with ketorolac for transversus abdominis plane (TAP) block after gynecological laparoscopic surgery. MATERIAL AND METHODS This randomized, observer-blind trial recruited 153 patients who underwent gynecological laparoscopic surgery. Patients were randomly assigned to receive bupivacaine combined with ketorolac 15 mg/side for TAP block (TK group), bupivacaine for TAP block and 30 mg postoperative intravenous ketorolac (T group), or 30 mg postoperative intravenous ketorolac alone (C group). The primary endpoints included consumption of sufentanil for 24 h postoperatively, actual press times of the patient-controlled analgesia (PCA) pump, and effective press times of the PCA pump, whereas the secondary endpoints included numerical rating scale (NRS) pain scores at rest and during activity, satisfaction with analgesia, episodes of nausea and vomiting and length of hospital stay. RESULTS Sufentanil consumption, actual press times of the PCA pump, and effective press times of the PCA pump were lower in the TK and T groups than in the C group. NRS scores at rest and during activity at 1, 2, 4, 6, and 24 hours were significantly lower in the TK and T groups than in the C group. The TK and T groups showed greater satisfaction with analgesia than the C group, while the TK group showed greater overall satisfaction than the C group. Lengths of stay, rates of nausea and vomiting, and venting times did not differ significantly among the three groups. CONCLUSIONS Combined ketorolac and bupivacaine as TAP block improved the effectiveness of analgesia without increasing adverse events. Trial registration number: ChiCTR1900022577.

Introduction: Sufentanil is a selective µ-opioid agonist, used intravenously and intrathecally for moderate to severe acute pain. Sublingual sufentanil nanotablets have been developed; 15 mcg tablet for a patient-controlled analgesia device and 30-mcg tablet for a single-dose device administered by a healthcare professional. Dosing interval is a minimum of 20 min for a 15 mcg tablet and a treatment duration of up to 72 hours. The single 30-mcg nanotablet dosing interval is 1 hour. Mean plasma elimination half-life is 13 hours and bioavailability 47-57% after the first sublingual sufentanil tablet., Areas Covered: This review focuses on the effectiveness, safety, and feasibility of sublingual sufentanil 30-mcg single dose suspended by a healthcare professional for the management of moderate to severe acute pain. A few Phase 4 studies concerning the sublingual sufentanil tablet system containing 15-mcg nanotablets are also reviewed., Expert Opinion: Sufentanil sublingual 30-mcg nanotablets provide effective pain relief in various acute moderate to severe pain states. The safety profile of sublingual sufentanil 30 mcg is typical to opioids nausea, vomiting, and sedation being the most common ones. Sublingual sufentanil 30-mcg nanotablet has the potential for efficient moderate to severe pain management in supervised healthcare facilities.

Background: Hyperuricemia is considered a risk factor for increased postoperative complications and adverse functional outcomes in a variety of orthopedic surgeries. The purpose of this retrospective study was to investigate the clinical efficacy of patients with different uric acid levels after elbow arthrolysis., Methods: The study included 131 patients with post-traumatic elbow stiffness who underwent arthrolysis between March 2014 and March 2016. All patients were divided into 4 groups based on the preoperative serum level of uric acid (UA). The quartile method was used for grouping patients, including 33 in Q1 (UA <293 μmol/L), 34 in Q2 (293-348 μmol/L), 32 in Q3 (348-441 μmol/L), and 32 in Q4 (441-710 μmol/L). At baseline and each time point of follow-up, functional performance, Mayo Elbow Performance Score, visual analog scale for pain, and complications were evaluated., Results: Preoperative data were not significantly different among the 4 groups (Q1, Q2, Q3, and Q4). At the final follow-up, the following data showed significant differences among the 4 groups: extension (P = .031), flexion (P = .008), range of motion (P = .003), Mayo Elbow Performance Score (P = .011), and visual analog scale (P = .032). Interestingly, patients in the Q4 group had the poorest clinical outcomes. However, no significant differences were found among the 4 groups in new onset or exacerbation of nerve symptoms (P = .919), reduced muscle strength (P = .536), instability (P = .567), or infection (P = .374) at the last follow-up., Conclusion: This study confirms that in patients with post-traumatic elbow stiffness, abnormal serum uric acid metabolism was a risk factor for poor performance and postoperative pain after arthrolysis. Therefore, detecting the preoperative serum uric acid levels of the patients would be helpful for evaluating the postoperative outcomes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In surgical procedures, tissue damage results in the release of a number of bioactive substances. Calcitonin gene-related peptide (CGRP) is a peptide released from sensory nerves, which determines its role in pain sensation. Its distribution in tissues deter-mines its role as a primary afferent neurotransmitter., Aim: To determine the effect of CGRP on postoperative pain and reactive inflammatory process after surgical removal of impacted mandibular third molars, as well as the factors that have influence upon the perception of pain., Materials and Methods: Forty patients with bilaterally impacted mandibular third molars were included in the study. Venous blood samples were collected before and 24 hours after the surgical procedure in order to test their serum levels of CGRP and procalcitonin. Two weeks later the procedure was repeated. The difficulty of the surgical procedure, its duration and complications were assessed in all patients., Results: The influence of some of the studied factors upon postoperative pain was established. Differences in the sensation of pain between the two sexes were found when comparing pain intensity reported by the patients. Significant difference between pain inten-sity after the 1st and 2nd surgical procedures (6 hours) was found in females (Z=2.63, p=0.009;), whereas in males the difference was observed at 24 hours (Z=1.99; p=0.047). Regarding the existence of sex-related association, а significant, strong positive correlation between CGRP levels after the 1st and 2nd surgical procedures (24 hours) was found in males (rxy=0.78; p=0.004), whereas in females this correlation was also significant, although moderately significant (rxy=0.44; p=0.020). CGRP levels at the first and second extractions were generally similar in males, and not as much in females. We proved significantly moderate positive association between CGRP and pulse levels measured before the second surgery (rxy=0.37, p=0.021)., Conclusion: The results of our study suggest a significant role of CGRP in reactive (neurogenic) inflammation., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although total joint replacement (TJR) surgery is considered as the most effective treatment for advanced osteoarthritis (OA) patients, up to one-third of patients reported unfavorable long-term post-operative pain outcomes. We aimed to identify metabolic biomarkers to predict non-responders to TJR using a metabolomics approach. TJR patients were recruited and followed-up at least 1-year post-surgery; TJR outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales. Targeted metabolomic profiling was performed on plasma samples collected pre-surgery and pairwise metabolite ratios, as proxies for enzymatic reactions, were calculated. Association tests were performed between each metabolite ratio and non-responders. The metabolome-wide significance was defined as p < 2 × 10 -5 . A total of 461 TJR patients due to primary OA were included in the analysis. Fifteen percent of patients were classified as pain non-responders; 16% were classified as function non-responders. Lower baseline WOMAC pain and function scores were significantly associated with pain and function non-responders, respectively (both p < 0.03). Two metabolite ratios were significantly associated with pain non-responders; acetylcarnitine (C2) to phosphatidylcholine acyl-alkyl C40:1 (PC ae C40:1) was five times higher in pain non-responders whereas phosphatidylcholine diacyl C36:4 (PC aa C36:4) to isoleucine was twenty one times lower in pain non-responders than responders (all p ≤ 1.93 × 10 -5 ). One metabolite ratio, glutamine to isoleucine, was significantly lower in function non-responders than responders (eight times lower; p = 1.08 × 10 -5 ). Three metabolite ratios (C2 to PC ae C40:1, PC aa C36:4, and glutamine to isoleucine) related to inflammation and muscle breakdown could be considered as novel plasma markers for predicting non-responders to TJR and warrant further investigation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:793-802, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: This study aims to investigate the efficiency of fascia iliaca compartment block (FICB) combined with dexmedetomidine (DEX) in postoperative and inflammation management for elder patients after total hip arthroplasty., Methods: The present randomized controlled study included a total of 119 elder patients who received total hip arthroplasty in our hospital from March 2016 to December 2018. These patients were divided into three groups: control group, patients received routine general anesthesia; FICB group, patients received additional FICB after surgery; and combined group, patients received both pre-treatment of DEX and post-treatment of fascia iliaca compartment block. The serum levels of interleukin (IL)-1β, IL-6, and C-reactive protein (CRP) were measured by ELISA. The visual analog scale (VAS) score was measured at 12, 24, 48, and 72 h after surgery, and the patient-controlled intravenous analgesia (PCIA) pressing time within 48 h after surgery was also recorded. The Pittsburgh sleep quality index (PSQI) was used to measure the sleep quality before and at 1 month after surgery., Results: The VAS scores were significantly lower in patients in the combined group, when compared with the other two groups, at 12, 24, 48, and 72 h after surgery. In addition, the VAS scores at all time points were significantly lower in the FICB group than the control group. The PCIA pressing times were also remarkably lower in the combined group. At 4, 24, 48, and 72 h after surgery, the serum levels of these inflammatory factors were the lowest in the combined group, and the PSQI scores were significantly lower in the combined group, when compared with the other two groups, while the control group had the highest PSQI scores among the three groups. There was no severe side effects and significant difference observed., Conclusion: FICB combined with DEX reduced the postoperative pain, improved the sleep condition, and decreased the serum levels of inflammatory factors after total hip arthroplasty.

Background: Preoperative patients' vulnerabilities such as physical, social, and psychological are implicated in postoperative pain variability. Nevertheless, it is a challenge to analyze a patient's psychological profile in the preoperative period in a practical and consistent way. Thus, we sought to identify if high preoperative emotional stress, evaluated by the Brief Measure of Emotional Preoperative Stress (B-MEPS) scale is associated with higher postoperative pain levels and poor rehabilitation in patients submitted to intermediate or major surgery. Moreover, the possible neurobiological or neurophysiological mechanisms implicated in high preoperative emotional stress, evaluated through preoperative quantitative sensory pain tests and serum biomarkers BDNF and S100B were investigated., Methods: We conducted a prospective, observational, cohort study of ASA 2 and 3 adult patients undergoing major urologic, gynecologic, proctologic and orthopedic surgeries from March 2017 to March 2018. B-MEPS and Central Sensitivity Inventory were evaluated preoperatively, followed by a sequence of experimental pain tests and serum biomarkers collection. Postoperative evaluation carried out within the first 48 hours after surgery comprehended pain at rest and movement-evoked pain, and the consumption of morphine. Quality-of-Recovery was also evaluated in the 3rd postoperative day., Results: 23 (15%) out of 150 patients included in the study presented high emotional preoperative stress. Variables significantly related to preoperative stress were: previous psychiatric diagnosis and Central Sensitization Inventory result. Mean movement-evoked pain in the first 12 to 48 hours was 95-105% higher than pain at rest. A mixed model for repeated measures showed a sustainable effect of B-MEPS as a movement-evoked pain predictor. Previous pain, cancer surgery, and preoperative pressure pain tolerance were also independent predictors of postoperative pain. Moderate to severe postoperative movement-evoked pain was predictive of poor rehabilitation in 48 hours after surgery., Conclusion: We confirmed that a brief screening method of preoperative emotional states could detect individuals prone to experience severe postoperative pain. Specific interventions considering the stress level may be planned in the future to improve perioperative outcomes., Competing Interests: The authors have declared that no competing interests exist.

Introduction: One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low-molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain., Materials and Methods: The study was designed as a nested case-control study within a cohort of women treated for endometrial cancer with robot-assisted laparoscopic hysterectomy. Twenty-six women with chronic postoperative pain were matched on age and body mass index with fifty-two controls without chronic postoperative pain, and metabolic profiling of preoperatively drawn blood samples from a biobank was performed by means of nuclear magnetic resonance spectroscopy., Results: Nineteen metabolites, including cholesterol, cholesteryl ester, linoleic acid, phospholipids, lipids, and triglycerides had statistically significant higher concentrations in a subgroup of patients who would develop chronic postoperative pain on a later stage compared to the group of patients who would not develop chronic postoperative pain ( p  <   0.05). A sparse Partial Least Squares-Discriminant Analysis model explained 38.1% of the variance and had a predictive accuracy of 73.1%., Conclusions: This explorative study substantiates the hypothesis that certain lipids, lipoproteins, and fatty acids are associated with chronic postoperative pain.

Objective: Post-operative chronic post-thoracotomy pain (CPTP) has been linked to restrictions in mobility and daily activities. However, its potential causes and optimal therapy have not been well characterized. Here, the purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) in CPTP rats and its underlying mechanism., Methods: Initially, rat models of CPTP were established. Then, the mechanical withdrawal threshold (MWT) was measured after intrathecal injection of TLR4 antagonist (LPS-RS), TLR4 agonist (LPS-PG), or caspase-1 inhibitor (Ac-YVAD-CMK) in CPTP rats. Levels of TNF-α, IL-6 and IL-1β in the spinal dorsal horn (SDH) were measured by ELISA. TLR4 and caspase-1 were located by immunofluorescence double staining. TLR4 and caspase-1 levels were assessed by qRT-PCR and Western blot., Results: TLR4 and caspase-1 were up-regulated in SDH of CPTP rats. Compared with Sham and non-CPTP groups, MWT was effectively decreased while TNF-α, IL-6 and IL-1β in SDH were increased in CPTP group. Moreover, intrathecal injection of TLR4 antagonist or caspase-1 inhibitor significantly elevated MWT expression and reduced levels of TNF-α, IL-6 and IL-1β in SDH. Additionally, high expression of TLR4 promoted mechanical hyperalgesia and inflammatory response, while intrathecal injection of a mixture of caspase-1 inhibitor and TLR4 agonist reversed the alleviation of caspase-1 inhibitor on the mechanical hyperalgesia and inflammatory response. TLR4 and caspase-1 were co-located in neurons., Conclusion: TLR4 aggravated CPTP in rats by mediating activation of caspase-1 in SDH., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement., Methods: Serum samples, collected preoperatively from 136 knee osteoarthritis patients, were analyzed for 21 circulatory microRNAs. Pain intensity was assessed using a visual analog scale before and one year after total knee replacement. Patients were divided into a low-pain relief group (pain relief percentage <30%) and a high-pain relief group (pain relief percentage >30%) based on their pain relief one year after total knee replacement, and differences in microRNAs expression were analyzed between the two groups., Results: We found that three microRNAs were preoperatively dysregulated in serum in the low-pain relief group compared with the high-pain relief group. MicroRNAs hsa-miR-146a-5p, -145-5p, and -130 b-3p exhibited fold changes of 1.50, 1.55, and 1.61, respectively, between the groups (all P values < 0.05). Hsa-miR-146a-5p and preoperative pain intensity correlated positively with postoperative pain relief (respectively, R = 0.300, P = 0.006; R = 0.500, P < 0.001)., Discussion: This study showed that patients with a low postoperative pain relief present a dysregulation of circulating microRNAs. Altered circulatory microRNAs expression correlated with postoperative pain relief, indicating that microRNAs can serve as predictive biomarkers of pain outcome after surgery and hence may foster new strategies for preventing chronic postoperative pain after total knee replacement (TKR).

Regional anesthetic techniques are important components of successful multimodal analgesic strategies. When used successfully, truncal nerve blocks of the chest wall, abdomen, and, paraneuraxial nerves, in combination with other analgesic modalities, may offer similar analgesic efficacy as neuraxial techniques, which are associated with a greater risk profile. Moreover, in comparison to neuraxial techniques, truncal nerve blocks are relatively simple to perform and technically straightforward to learn. The transversus abdominus plane (TAP) block is often incorporated into the multimodal analgesia regimen for surgical patients undergoing various abdominal and gynecological procedures. Rectus sheath blocks (RSB) were originally introduced to help relax the anterior abdominal wall during surgery and as an adjunct pain therapy. With the advancement of technology and the development of ultrasound guided techniques, RSB now have a more ubiquitous role and have been shown to decrease postoperative pain and opioid consumption. Different variations of the quadratus lumborum block may provide visceral and sensory analgesic coverage. Moreover, truncal blocks, including ilioinguinal, iliohypogastric, pectoralis nerve (PECS) blocks, serratus anterior, intercostal, and erector spinae plane blocks, have gained routine clinical use for various surgeries. In this review, we discuss the techniques, anatomy, indications, complications, and benefits of truncal nerve blocks commonly used in clinical practice., (Published by Elsevier Ltd.)

Introduction: Cesarean delivery is the most common surgery in obstetrics, and pain relief after cesarean section is an important concern for obstetricians and their patients. Objective: The aim of this study was to evaluate the relationship between serum progesterone level and pain perception after cesarean delivery. Method: The study was performed as a prospective cohort study on 166 pregnant women who were candidates for elective cesarean delivery due to previous cesarean section. Before surgery, serum progesterone level was measured. Pain score of women was evaluated 4, 8, 12, and 24 h after surgery using visual analog scale (VAS) score, and correlation between progesterone level and pain was evaluated. Results: The median value of serum progesterone was 119.45 ng/ml. Mean pain score in hours 4, 8, 12, and 24 were 6.80 ± 2.11, 5.31 ± 1.48, 3.89 ± 1.68, and 2.30 ± 1.26, respectively. The women were divided according to mean progesterone level of 119.45 ng/ml into two groups of high progesterone level (≥119.45) and low progesterone level (<119.45), and the pain score was evaluated in different times (hour 4, 8, 12, and 24) for both levels of progesterone. The mean pain score in the 4, 8, 12, and 24 h were significantly lower in high progesterone group (progesterone level ≥119.45). The number of women with low pain score (less than five) in hours 12 and 24 was significantly higher in high progesterone level group. With increasing BMI, progesterone level was lower and women with higher BMI, had a higher pain score in hours 4, 8, 12, and 24, while women with lower BMI had a lower pain score during the same hours. ( p  = .004, r  = 0.223; p  = .004, r  = 0.223; p  = .039, r  = 0.160; and p  = .007, r  = 0.207). Progesterone level and BMI ( p  = .025, r  = - 0.174), and progesterone level and pain score in hours 4, 8, 12, and 24 ( p  = .000, r  = - 0.324; p  = .000, r  = - 0.474; p  = .000, r  = - 0.329; and p  = .000, r  = - 0.417, respectively) showed a negative significant correlation. Putting three variables of age, gestational age, and BMI in a multiple regression model, progesterone level showed significant negative correlation with the pain score in hour 4 ( p  = .000, r  = - 0.305), hour 8 ( p  = .000, r  = - 0.461), hour 12 ( p  = .000, r  = - 0.328), and hour 24 ( p  = .000, r  = - 0.409). Conclusions: Serum progesterone level showed a negative correlation with the pain score after cesarean section.

Purpose: The prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3-72 months., Methods: A single dose of 10 mg/kg metamizole was administered intravenously for postoperative analgesia. Pharmacokinetic samples were drawn at predefined time points. Pharmacokinetics of the main active metabolite 4-methylaminoantipyrine and three other metabolites was characterized by both non-compartmental and population pharmacokinetic analysis. AUC 0-inf of 4-methylaminoantipyrine was calculated by non-compartmental analysis for two age cohorts (3-23 months, 2-6 years) and compared with the 80-125% range of adult dose-adjusted reference exposure (AUC ref ). Population pharmacokinetic analysis investigated age and weight dependency of the pharmacokinetics and optimal dosing strategies to achieve equivalent adult exposure., Results: A total of 25 children aged 5 months-5.8 years (7.8-24.8 kg) with at least one concentration sample were included; 19 children had ≥ 5 predefined samples up to 10 h after metamizole dose administration. AUC 0-inf of 4-methylaminoantipyrine in children 2-6 years was 29.9 mg/L/h (95% CI 23.4-38.2), significantly lower than AUC ref (80-125% range 39.2-61.2 mg/L/h). AUC 0-inf of 4-methylaminoantipyrine in infants < 2 years was 43.6 mg/L/h (95% CI 15.8-119.0), comparable with AUC ref , while infants < 12 months showed increased exposure. Observed variability could be partially explained by covariates weight and age., Conclusions: Age-related changes in pharmacokinetics of 4-methylaminoantipyrine requires reduced weight-based IV dosing in infants < 1 year compared with infants and children up to 6 years (5 versus 10-20 mg/kg) to achieve equivalent adult exposure., Trial Registration: ClinicalTrials.gov identifier: NCT02660177 .

Oxytocin has known antinociceptive effects and is upregulated perinatally. This pilot study investigated the association of plasma oxytocin and postcesarean incisional pain. Plasma samples from 18 patients undergoing elective cesarean delivery were drawn at 1 hour preoperatively and 1 and 24 hours postoperatively and analyzed by using enzyme-linked immunosorbent assay. Pain was assessed at 1 day, 8 weeks, 3 months, and 6 months postoperatively. Incisional pain at 24 hours was inversely correlated with 1- and 24-hour oxytocin levels, with higher plasma oxytocin associated with lower pain (ρ, -0.52 and -0.66; P < .05).

Objective: To compare the effects of two different intraoperative CO 2 pressures (8 and 15 mmHg) during laparoscopic hysterectomy for benign uterine pathologies in terms of postoperative abdominal and shoulder pain, laparoscopy-mediated vegetative alterations, pain medication requirement, arterial CO 2 pressure (pCO 2 ), surgical parameters, and safety., Design: Prospective randomised controlled study., Setting: German university hospital., Population: Female patients undergoing laparoscopic hysterectomy for benign uterine pathologies., Methods: Patients were randomised to a standard pressure (SP; 15 mmHg, control) or low-pressure (LP; 8 mmHg, experimental) group., Main Outcome Measures: Primary outcomes were postoperative abdominal and shoulder pain intensities, measured via numeric rating scale (NRS) and vegetative parameters (fatigue, nausea, vomiting, bloating) at 3, 24, and 48 hours postoperatively. Secondary outcomes were pain medication requirement (mg) and arterial pCO 2 (mmHg). Surgical parameters and intra- and postoperative complications were also recorded., Results: In total, 178 patients were included. Patients in the LP group (n = 91) showed significantly lower postoperative abdominal and shoulder pain scores, fewer vegetative alterations, lower pain medication requirements, a shorter postoperative hospitalization, and lower intra- and postoperative arterial pCO 2 values compared with the SP group (n = 87; P ≤ 0.01). No differences in intra- and postoperative complications were observed between groups., Conclusions: Low-pressure laparoscopy seems to be an effective and safe technique for the reduction of postoperative pain and laparoscopy-induced metabolic and vegetative alterations following laparoscopic hysterectomy for benign indications., Tweetable Abstract: Low-pressure laparoscopy seems to be an effective and safe technique for reduction of pain following laparoscopic hysterectomy., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Background: Ketorolac tromethamine has been used for joint infiltration by the orthopedic surgeons as a part of postoperative multimodal analgesia. The objective of this study is to investigate the pharmacokinetic properties of S (-) and R (+) enantiomers of ketorolac in adult patients undergoing total hip (THA) and knee arthroplasty (TKA)., Methods: Adult patients with normal preoperative renal function received a periarticular infiltration of 30 mg of ketorolac tromethamine along with 100 mL of 0.2% ropivacaine and 1 mg of epinephrine at the end of their THA or TKA surgery. Blood samples were taken from a venous cannula at various time points after infiltration. Pharmacokinetic modeling was performed using PMetrics 1.5.0., Results: From 18 participants, 104 samples were analyzed. The peak plasma concentration for S (-) ketorolac was found to be lower than that of R (+) ketorolac, for both THA (0.19-1.22 mg/L vs 0.39-1.63 mg/L, respectively) and TKA (0.28-0.60 mg/L vs 0.48-0.88 mg/L, respectively). The clearance of the S (-) ketorolac enantiomer was higher than R (+) ketorolac (4.50 ± 2.27 vs 1.40 ± 0.694 L/h, respectively)., Conclusions: Our study demonstrates that with periarticular infiltration, S (-) ketorolac was observed to have increased clearance rate and highly variable volume of distribution and lower peak plasma concentration compared to R (+) ketorolac.

Background: The term "Immunonutrition" (IMN) describes the enteral administration of certain substrates with a theoretical immunomodulating function. From all the elements conforming these IMN formulas, Omega-3 fatty acids (O3FA) are hypothesized to be the most important component for immunomodulation, with increased anti-inflammatory and antioxidant effect., Patients and Methods: A prospective randomized clinical trial of all the patients undergoing laparoscopic Roux-en-Y gastric bypass was performed. Patients were randomly assigned into 2 groups: those patients receiving a preoperative balanced energy high-protein formula (Control Group) and those ones who received the same preoperative nutritional formula enriched with O3FA (Experimental Group). In both groups, there was a restriction to 900 Kcal/day. Nutritional intervention started 10 days before surgery and was maintained up to 8 h before the surgical act. Preoperative weight loss, postoperative pain, complications and acute phase reactants were investigated., Results: 40 patients were included in the study, 20 in each group. Preoperative excess weight loss (EWL) with the prescribed treatment was 10.6 ± 7.7% in Control Group and 14.1 ± 5.8% in the Experimental Group (p = 0.024). Mean postoperative pain was 25 ± 9.2 mm in Control group and 10,9 ± 4,4 mm in Experimental Group (p = 0.015). CRP determined 24 h after surgery was significantly lower in the Experimental Group than in the Control Group. There were not significant differences in complications, mortality or readmission rates between groups., Conclusions: The use of a nutritional supplement enriched with O3FA is associated with a greater preoperative weight loss, reduced postoperative pain and decreased postoperative levels of C reactive protein., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: In our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3 months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRG STIM ), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways., Methods: Blood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3 months L4-DRG STIM using PANTHER™ pathway enrichment analysis tool., Results: Pathway enrichment analyses tools (GOrilla™ and PANTHER™) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRG STIM . Seven genes including TLR1, FFAR2, IL1RAP, ILRN, C5, PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL-17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated., Conclusions: In our sub-group analysis of L4-DRG STIM treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients. Trial registration The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00011267.

Background: Postoperative visceral pain is common after surgery and previous studies have demonstrated that oxycodone is an effective treatment. In this study, we compared the effects of preemptive oxycodone to equal dose of sufentanil on postoperative pain and serum level of inflammatory factors (TNF-α, IL-6, IL-10) after laparoscopic cholecystectomy., Methods: Forty patients undergoing laparoscopic cholecystectomy were randomized into preemptive oxycodone group or preemptive sufentanil group. Patients were given either oxycodone 0.1 mg/kg (oxycodone group, n = 20) or sufentanil 0.1 μg/kg (sufentanil group, n = 20) for preemptive analgesia. We evaluated pain/sedation scores at 0 h, 0.5 h, 2 h, 4 h, 6 h, 8 h and 24 h after surgery and measured serum concentrations of TNF-α, IL-6 and IL-10 before surgery and at 0 h, 6 h and 24 h after surgery., Results: Twenty patients were recruited in each group. Numerical rating scale (NRS) of visceral pain in the oxycodone group at 2 h when resting (0.5(0,2.75) vs 3(2,4), P = 0.008) and moving (0.5(0,3) vs 3(2.25,4), P = 0.015) and 4 h when moving (2(0,3) vs 3(0,4.75), P = 0.043) after surgery were significantly lower than the sufentanil group. Serum concentrations of TNF-α at 6 h (38.68 ± 10.49 vs 73.02 ± 16.27, P<0.001) and 24 h (43.12 ± 8.40 vs 74.00 ± 21.30, P<0.001) in the oxycodone group were lower than the sufentanil group., Conclusions: Preemptive oxycodone 0.1 mg/kg administration could effectively suppress visceral pain at 2 h and 4 h after surgery and had lower inflammatory marker, serum TNF-α, level when compared to equal dose of sufentanil., Trial Registration: Clinical trials registration number: ChiCTR-IOR-17013738 http://www.chictr.org.cn/showproj.aspx?proj=17346 . Date of registration: 6th December 2017.

Background: The purpose of this study was to compare the effects of scalp nerve block (SNB) and local anesthetic infiltration (LA) with 0.75% ropivacaine on postoperative inflammatory response, intraoperative hemodynamic response, and postoperative pain control in patients undergoing craniotomy., Methods: Fifty-seven patients were admitted for elective craniotomy for surgical clipping of a cerebral aneurysm. They were randomly divided into three groups: Group S (SNB with 15 mL of 0.75% ropivacaine), group I (LA with 15 mL of 0.75% ropivacaine) and group C (that only received routine intravenous analgesia). Pro-inflammatory cytokine levels in plasma for 72 h postoperatively, hemodynamic response to skin incision, and postoperative pain intensity were measured., Results: The SNB with 0.75% ropivacaine not only decreased IL-6 levels in plasma 6 h after craniotomy but also decreased plasma CRP levels and increased plasma IL-10 levels 12 and 24 h after surgery compared to LA and routine analgesia. There were significant increases in mean arterial pressure 2 and 5 mins after the incision and during dura opening in Groups I and C compared with Group S. Group S had lower postoperative pain intensity, longer duration before the first dose of oxycodone, less consumption of oxycodone and lower incidence of PONV through 48 h postoperatively than Groups I and C., Conclusion: Preoperative SNB attenuated inflammatory response to craniotomy for cerebral aneurysms, blunted the hemodynamic response to scalp incision, and controlled postoperative pain better than LA or routine analgesia., Trial Registration: Clinicaltrials.gov NCT03073889 (PI:Xi Yang; date of registration:08/03/2017).

Background: Preoperative oral carbohydrates has been suggested to attenuate insulin resistance and decrease postoperative complications. In this study, a vitamin-rich carbohydrate beverage was administered before surgery in an animal model to investigate its effects on the surgical stress response and S-100β levels., Methods: Thirty aged male Sprague-Dawley rats were randomly assigned to three groups: control group (n = 6), fasting group (n = 12), and carbohydrate-treated group (CHO group, n = 12). Rats in the control group were not given any treatment. Rats in the fasting group received splenectomy after 12 h of fasting. In the CHO group, rats were given 5 ml of vitamin-rich carbohydrate by gavage 2 h before surgery. Fasting plasma glucose, insulin, insulin resistance (HOMA-IR index, IRI), the S-100β protein level, and the inflammatory mediators IL-1β, IL-6 and TNF-α were assessed after surgery (postoperative day (POD) 1 and 3)., Results: Postoperative insulin resistance was significantly greater in the fasting group than in the control and CHO group. The median plasma S-100β level was significantly higher in the fasting group than in the control and CHO groups on POD 1. The median plasma IL-1β level was significantly lower in the CHO group than in the fasting group on POD 1; however, no other differences in the concentrations of immunological biomarkers of stress were found between the fasting group and the CHO group., Conclusions: Vitamin-rich carbohydrate pretreatment attenuated the metabolic aspect of the surgical stress response and decreased the level of plasma S-100β, which may decrease the risk of postoperative complications in elderly rats.

Background: Pro- and anti-inflammatory cytokines (adipokines) associated with adipose tissue can modulate inflammatory processes and lead to systemic inflammatory conditions such as metabolic syndrome. In the present pilot study, we investigated 3 major adipokines (leptin, adiponectin, and resistin) and 2 nonspecific proinflammatory cytokines (tumor necrosis factor α and interleukin-6) with regard to their association with postoperative pain intensity., Methods: We analyzed a total of 45 single-nucleotide polymorphisms of the adipokines in 57 patients with postlaparotomy pain. We adjusted for multiple testing to reduce the chance of false-positive results by controlling the false discovery rate. Serum levels of the adipokines and proinflammatory cytokines were measured in another 36 patients undergoing laparotomy. A stepwise multiple linear regression analysis using these measurements and opioid dosages as independent variables was performed to explore the factors associated with postoperative pain., Results: Only 1 variant of the resistin gene (rs3745367) demonstrated a significant association with postoperative pain (P < .002). Patients exhibiting homozygosity for the minor alleles (n = 7; numerical rating scale [NRS], 2.3 ± 1.3) demonstrated lower pain intensity compared with those exhibiting homozygosity for the major alleles (n = 29; NRS, 3.8 ± 1.0; P = .004) and heterozygosity for the minor alleles (n = 21; NRS, 4.2 ± 0.8; P < .001). Only serum resistin levels showed a positive association with postoperative pain., Conclusions: A genetic variant of resistin and serum resistin levels were associated with postoperative pain intensity, while other adipokines and cytokines exhibit no such association. Resistin can alter the inflammatory responses in postoperative wounds, although it could be a determinant factor that is independent of inflammatory processes. Resistin may be a novel marker for postoperative pain intensity.

This study aimed to evaluate pain scores, analgesic requirements, food intake and serum inflammatory cytokines in cats before and after clinically recommended dental treatment. Twenty-four cats were included in a prospective, blinded clinical trial. Cats were equally divided into minimal (minimal dental treatment) or severe (multiple dental extractions) oral disease groups. They were admitted (day 0) and underwent oral examination/radiographs/treatment under general anesthesia (day 1; acepromazine-hydromorphone-propofol-isoflurane-meloxicam-local anesthetic blocks). Serum inflammatory cytokines were measured on days 0 and 6. Pain was scored using the Glasgow composite measure pain scale-feline (CMPS-F). Rescue analgesia was administered with hydromorphone if CMPS-F ≥ 5/20. Dry and soft food intake (%) during 3 minutes and 2 hours, and daily soft food were calculated. The Cochran-Mantel-Haenszel and Chi-square tests, Spearman's rank correlation and linear mixed models were used for statistical analysis (alpha = 0.05). Pain scores were significantly increased in cats with severe disease when compared with baseline (up to day 4) and minimal disease (all postoperative time points). Prevalence of rescue analgesia was significantly higher in severe (91.7%) than minimal disease (0%); analgesics were required up to day 3. Pain scores and frequency of rescue analgesia were significantly correlated with the number of tooth extractions, gingival and calculus index. Prevalence of rescue analgesia was significantly correlated with the number of missing teeth, teeth extractions and gingival index. Dry and soft food intake during 3 minutes, and dry food intake during 2 hours were significantly lower in the severe than minimal disease group throughout the study. Some cytokines differed between groups between day 0 and day 6 and were associated with the presence of tooth resorption and number of missing tooth and tooth fractures. Long-term analgesia is required after dental extractions in cats with severe oral disease. This condition reduces food intake and influences serum inflammatory cytokines., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To compare open Lichtenstein repair and laparoscopic transabdominal preperitoneal (TAPP) repair to treat primary unilateral hernia, regarding systemic inflammatory response, postoperative pain, and complications., Methods: A non-randomized prospective cohort study, with the preoperative and postoperative (24 hours) collection of blood samples for C reactive protein (CRP), interleukin 6 (IL-6), leukocyte and neutrophil analysis. Visual Analog Scale (VAS) was used to quantify the level of pain, and the operative time was correlated with the inflammatory response. VAS and CRP were also obtained on the 8th postoperative day., Results: Groups were homogeneous regarding preoperative characteristics. There were no differences between groups in 24h values of CRP, IL-6, leukocytes, neutrophils or VAS. Similarly, CRP and VAS did not differ between groups on the 8th postoperative day. However, the operative time for laparoscopic hernia repair was longer than the time for the open procedure. There was a weak correlation (r coefficient 0.31) between the duration of the surgical procedure and the VAS score at the eighth day., Conclusions: There were no statistically significant differences in the inflammatory response, pain scores, or complications between groups. We conclude that there is no advantage performing a primary unilateral hernia repair by laparoscopy.

Background: In recent decades, obesity has become a public health problem in many countries. The objective of this study was to evaluate the main joint and extra-articular manifestations related to spondyloarthritis (SpA) after bariatric surgery (BS) in a retrospective cohort., Methods: Demographic, clinical, laboratory and imaging data from nine patients whose SpA symptoms started after a BS have been described. Modified New York (mNY) criteria for ankylosing spondylitis (AS) and the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial (ax-SpA) and peripheral (p-SpA) spondyloarthritis were applied., Results: The mean weight reduction after BS was 49.3 ± 21.9 kg. The BS techniques were Roux-en-Y gastric bypass (n = 8; 88.9%) and biliopancreatic diversion with duodenal switch (n = 1; 11.1%). Four (44.4%) patients had no axial or peripheral pain complaints before BS, while the other four (44.4%) had sporadic non-inflammatory back pain that had been attributed to obesity. One patient (11.1%) had persistent chronic back pain. In all nine cases, patients reported back pain onset or pattern (intensity or night pain) change after BS (mean time 14.7 ± 18 months). In addition, 8 of them (88.9%) were human leukocyte antigen (HLA)-B27 positive. All nine patients could be classified according to ASAS criteria as ax-SpA and five (55.6%) patients were classified as AS, according to the mNY criteria., Conclusion: Our data highlight a temporal link between SpA onset symptoms and the BS, suggesting a possible causal plausibility between the two events.

Objective: This study aimed to investigate the preoperative level of serum leptin in cesarean section (C-section) patients with and without acute labor pain and its association with postoperative analgesic consumption and preoperative pain threshold., Materials and Methods: Preoperative leptin levels, preoperative pain threshold, postoperative analgesic consumption in the first 24 h, and postoperative pain severity (visual analog scale (VAS) scores at 1, 2, 4, 6, 12, and 24 h postoperatively) in C-section patients with labor pain (emergency C-section; n = 21) and without labor pain (elective C-section; n = 25) were compared., Results: There were no significant differences between the groups regarding the demographic characteristics. Leptin levels, postoperative VAS scores, and analgesic consumption were significantly higher in the group with labor pain, while the preoperative pain threshold was lower. Serum leptin levels correlated negatively with pain threshold and positively with postoperative analgesic consumption. Multiple linear regression analyses in our study revealed that the preoperative leptin levels and having an emergency C-section independently affected the postoperative analgesic consumption and preoperative pain threshold, whereas their combined effects on these parameters were statistically not significant., Conclusion: Preoperative levels of serum leptin were higher in C-section patients with labor pain than in those without labor pain, and increased serum leptin levels were associated with decreased preoperative pain threshold and increased postoperative analgesic consumption in our study population. Postoperative analgesic requirements may vary among patients, and their requirements might be predicted using preoperative indicators. Serum levels of leptin might be one such indicator and this warrants further studies with larger sample sizes., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background and Objectives: Neutrophil to lymphocyte ratio is a simple, cost-effective and easily applicable inflammation indicator that is being used frequently in mortality, morbidity and prognosis studies in the recent years. We evaluated the relationship between neutrophil to lymphocyte ratio and postoperative pain in patients undergoing total hip arthroplasty and total knee arthroplasty., Material and Methods: We included 101 patients who preferred spinal anesthesia and intravenous patient-controlled analgesia in accordance and divided them into two groups, total hip arthroplasty and total knee arthroplasty. We recorded demographic information, duration of operation, length of hospital stay, analgesics consumption, neutrophil to lymphocyte ratio results and postoperative pain using Visual Analog Scale., Results: The morphine consumption of the patients was as follows in group total hip arthroplasty and total knee arthroplasty: at the 4th hour: 7.38mg, 7.80mg; 8th hour: 12.19mg, 13.29mg; 12th hour: 16.94mg, 19.18mg; 24th hour: 25.97mg, 27.98mg; 48th hour: 36.38mg, 39.59mg. The Visual Analog Scale scores of the patients was as follows in group total hip arthroplasty and total knee arthroplasty: at the 4th hour: 4.10, 4.51; 8th hour: 3.02, 3.43; 12th hour: 2.29, 2.55; 24th hour: 1.90, 1.87; 48th hour: 1.08, 1.13. In group total hip arthroplasty, we found a statistically significant association between postoperative neutrophil to lymphocyte ratio and the Visual Analog Scale values on the 48th hour in a positive direction (r=0.311; P=0.031; P<0.05)., Conclusion: Neutrophil to lymphocyte ratio can be accepted as a relatively objective method for the diagnosis of postoperative pain., (Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Aim: To determine the relationship between the serum urate (SU) level, neutrophil / lymphocyte ratio (NLR), and pain severity using preoperative and postoperative visual analogue scale (VAS) scores in patients with lumbar disc herniation (LDH)., Material and Methods: This single-center, cross-sectional study included 20 consecutive patients who were operated for LDH by the same surgeon. The patients'pre- and postoperative UA levels, NLRs, and intensity severity VAS scores were investigated. Preoperative magnetic resonance imaging (MRI) findings, serum UA levels, and neutrophil and lymphocyte counts were recorded. Pain severity was recorded preoperatively and at 6 months postoperatively. Effects of the preoperative SU levels and NLRs on the pre- and postoperative VAS scores were statistically assessed., Results: Statistically significant positive correlation coefficients were determined between NLR and the preoperative and postoperative VAS scores. Negative correlation coefficients were found between the SU levels and preoperative VAS scores; in contrast, positive correlation coefficients were found between the SU levels and the postoperative VAS scores., Conclusion: Our results demonstrate the importance of not ignoring the serum UA level and NLR in pre- and postoperative pain in patients with LDH. Nevertheless, further extensive studies are warranted.

Pain increased the number of free radicals in the body. Previously, we studied changes mainly in oxygen and nitroxide free radicals and described these changes relative to the lipids and saccharides. In this article we focus on changes relative to proteins. Assessment of AGE products (advanced glycation end-products) was carried out by measuring fluorescence. Patients were divided into two groups: 15 patients with acute pain and 17 patients with chronic pain. Acute pain was associated with a variety of surgical procedures and patients were examined before and after surgical procedures. The group of patients with chronic pain suffered from various types of chronic pain, but mainly back pain. In patients with acute pain, total protein (TP) decreased after surgery, as did the level of AGE and the AGE/TP ratio. Nonetheless, post-operative pain increased. In patients with chronic pain, neither total protein, AGE, or AGE/TP changed, despite significant pain relief being reported after treatment. Changes in proteins, as biochemical markers, before and after pain treatment did not show any significant changes. In patients with acute pain, the recorded changes only lasted for 3-5 days after the operation. While in chronic pain, there were no significant changes at all. The assumption that changes in proteins, as biomarkers, would have the same importance as changes in lipids and saccharides was not proven.

Backgroupd: This study investigated the plasma fentanyl concentration and efficacy of transdermal fentanyl patch (TFP) (25 μg/h) in the management of acute postoperative pain., Methods: Patients undergoing laparoscopic cholecystectomy were randomly allocated to 2 groups. The TFP group (n = 30) received a single TFP 25 μg/ h to the anterior chest wall 14 h before operation. The IV group (n = 30) received a placebo patch. After the operation, intravenous fentanyl infusion (25 μg/h) was begun with loading dose 25 μg in the IV group and only normal saline in the TFP group. Plasma fentanyl levels were measured at admission, 1, 6, 12, 24, and 48 h postoperatively. Pain severity and adverse effects were evaluated too., Results: The fentanyl level peaked 1 h after operation in the TFP group (3.27 ± 0.34 ng/mL) and 24 h postoperatively in the IV group (2.9 ± 0.42 ng/mL). Pain scores and the use of rescue analgesics were not significantly different between 2 groups. Respiratory depression was not happened in both groups., Conclusions: The TFP (25 μg/h) affixed 14 h before surgery reached a higher constant concentration than the same dose setting of a constant IV infusion of fentanyl after surgery. Although the concentration of fentanyl was higher than those of previous researches, there was no respiratory depression. But, there was no advantage of reducing pain score and the use of rescue analgesics., Clinical Trial Registration: (available at: http://cris.nih.go.kr, KCT0002221).

Background and Objectives: Although intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine., Methods: Altogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group): pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non-protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined., Results: Results were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 μg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 μg/L, respectively; P < 0.01). Apparent volume of distribution and clearance were higher in the lipid group than in control subjects (211 ± 35 vs 170 ± 21 L and 35.1 ± 8.0 vs 25.8 ± 2.6 L/h, respectively; P < 0.05). Triglyceride level was significantly higher at the end of lipid infusion than baseline values (7.59 ± 1.32 vs 1.34 ± 0.39 mmol/L; P < 0.01)., Conclusions: Lipid pretreatment increased the apparent volume of distribution and clearance and decreased the maximum total and free levobupivacaine concentrations, thus offering a reasonable explanation for the effects of lipids on local anesthesia-related toxicity in humans. Rapid lipid infusion induced hypertriglyceridemia without other apparent risks in this study., Clinical Trial Registration: This study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-14005203.

Background: The impact of tramadol in children given acetaminophen-ibuprofen combination therapy is uncertain in acute pediatric pain management. A model describing the interaction between these three drugs would be useful to understand the role of supplemental analgesic therapy., Methods: Children undergoing tonsillectomy were given oral paracetamol and ibuprofen perioperatively. Blood was taken for paracetamol and ibuprofen drug assay on up to six occasions over 6 h after the initial dose. Tramadol was administered by caregivers for unacceptable postoperative pain. Pain was measured using the Parent's Postoperative Pain Measurement rating two hourly on the first postoperative day. A first-order absorption, one-compartment linear model with first-order elimination was used to describe acetaminophen and ibuprofen disposition. Analgesia was described using an E MAX model extended for three drugs, assuming additive effects. Curve fitting was performed using nonlinear mixed effects models., Results: Pharmacodynamic parameter estimates, expressed using fractional Hill equation, were maximum effect (E MAX ) 0.65 (95%CI 0.54, 0.74), the concentration of acetaminophen associated with 50% of the maximal drug effect (C 50, ACET ) 7.06 (95%CI 7.03, 7.72) mg/L, and the ibuprofen C 50 (C 50, IBU ) 3.95 (95%CI 2.57, 7.53) mg/L. The Hill coefficient was 1.48 (95%CI 0.92, 2.62) and an interaction term was fixed at zero (additivity). The half-time (t 1/2 keo) for equilibration between the plasma and effect site was 0.34 hour (95%CI 0.23, 1.98) for acetaminophen and 1.04 hour (95%CI 0.75, 1.77) for ibuprofen. Tramadol had a C 50, TRAM of 0.07 (95%CI 0.048, 1.07) mg/L with a t 1/2 keo, TRAM 1.78 hour (95%CI 1.06, 1.96)., Conclusion: Ibuprofen has an EC 50 for analgesia in children similar to that of adults (3.95 mg/L; 95%CI 2.57-7.53, vs 5-10 mg/L adults). The maximum effect from combination therapy (ie, 65% reduction in pain score) achieves satisfactory analgesia with commonly used doses but increased dose adds little additional benefit. The addition of tramadol to this analgesic mixture prolongs analgesia duration., (© 2018 John Wiley & Sons Ltd.)

Background: Opioid usage is reportedly increased in patients with advanced cancer and low total cholesterol (TC). The aim of this study was to determine the effects of preoperative serum TC levels on postoperative opioid usage in patients undergoing laparoscopic gastric cancer surgery., Methods: We retrospectively analyzed the medical records of patients with gastric cancer who underwent laparoscopic gastrectomy at our institution between January 1, 2011 and July 31, 2017. We investigated the correlation between TC levels in the month before surgery and numeric rating scale (NRS) scores and opioid consumption on postoperative days (PODs) 0 to 3. The patients were stratified according to preoperative TC level (< 160 mg/dL, low; 160 to 199 mg/dL, medium; ≥ 200 mg/dL, high)., Results: TC and NRS scores (PODs 0, 1) for 1,919 eligible patients showed weak but significant positive coefficients (0.074 and 0.098 on POD 0 and POD 1, respectively, P < 0.01). After adjusting for confounders, there were no significant differences in postoperative NRS scores on PODs 0, 1, 2, or 3 or in oral morphine equivalents on PODs 0 to 3 according to TC level., Conclusion: Preoperative serum TC levels have no effect on pain outcomes in the 3 days following laparoscopic gastric surgery., (© 2017 World Institute of Pain.)