Brief Pain Inventory (BPI) Pain Survey Versus Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

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-1ß) 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.

Correlation Between Blood Levels of Cysteine Protease Caspase-1 (Casp1) and Pain Scores (NRS) Post-surgery: A Prospective Randomized Study of Patients With Cholelithiasis.

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-1ß, 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.

Plasma proteins and persistent postsurgical pelvic pain among adolescents and young adults with endometriosis.

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.

Metabolomic profiling of pediatric post-tonsillectomy pain: A proof-of-concept study.

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.

Preoperative angiotensin II type 2 receptor is a predictor for developing chronic post-surgical pain after total knee arthroplasty surgery.

OBJECTIVE: This study aimed to explore whether preoperative angiotensin II type 2 receptor (AT2R) 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 AT2R 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 AT2R 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 AT2R 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 AT2R level are at increased risk of developing CPSP following TKA. AT2R may serve as a candidate predictor for phenotyping CPSP in OA patients.

Effects of intravenous lidocaine, dexmedetomidine, and their combination on IL-1, IL-6 and TNF-α in patients undergoing laparoscopic hysterectomy: a prospective, randomized controlled trial.

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.

Observation of Complement Protein Gene Expression Before and After Surgery in Opioid-Consuming and Opioid-Naive Patients.

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.

Mechanism of Toll-like Receptor 4 on Chronic Post-thoracotomy Pain Via Caspase-1 Activation.

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-1ß 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-1ß 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-1ß 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.

Postoperative clinical outcomes and inflammatory markers after inguinal hernia repair using local, spinal, or general anesthesia: A randomized controlled trial.

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-1ß, 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.

IFN-γ Correlations with Pain Assessment, Radiological Findings, and Clinical Intercourse in Patient after Lumbar Microdiscectomy: Preliminary Study.

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.

Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

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).

The relationship between the level of µ-opioid receptor (µORs) and postoperative analgesic use in patients undergoing septoplasty: a prospective randomized controlled trial.

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).

An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia.

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.

Effect of the Combination of Ketorolac and Bupivacaine on Transversus Abdominis Plane Block for Postoperative Analgesia After Gynecological Laparoscopic Surgery.

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.

Correlation between CGRP Levels and the Neuropathic and Inflammatory Component of Postoperative Pain.

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.

An up-to-date overview of sublingual sufentanil for the treatment of moderate to severe pain.

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.

Effect of hyperuricemia on functional outcomes and complications in patients with elbow stiffness after open arthrolysis combined with hinged external fixation: a retrospective study.

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.

Chronic Postoperative Pain After Hysterectomy for Endometrial Cancer: A Metabolic Profiling Study.

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.

Combination of post-fascia iliaca compartment block and dexmedetomidine in pain and inflammation control after total hip arthroplasty for elder patients: a randomized control study.

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)-1ß, 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.

The Brief Measure of Emotional Preoperative Stress (B-MEPS) as a new predictive tool for postoperative pain: A prospective observational cohort study.

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.