Pain after laparoscopic endometriosis-specific vs. hysterectomy surgeries: A retrospective cohort analysis.

OBJECTIVES: To evaluate pain perception and analgesic use between patients who underwent endometriosis-specific laparoscopic surgery compared to laparoscopic hysterectomy. MATERIAL AND METHODS: This retrospective cohort study included women diagnosed with endometriosis who underwent laparoscopic surgery from 1/2019 to 11/2022. The control group consisted of premenopausal women who underwent laparoscopic hysterectomy, which was considered a similarly extensive surgery. Demographics, preoperative and post-operative data were compared between groups. Post-operative pain scores on a visual analogue scale (VAS) between 0 (no pain) and 10 (worst pain) were compared between groups for each post-operative day (POD). Standard pain relief analgesia on POD 0-1 included fixed intravenous treatment with paracetamol and intramuscular diclofenac. The need for additional analgesics (morphine or dipyrone) beyond the standard pain relief protocol was compared between groups. RESULTS: Among 200 patients who underwent laparoscopic surgery, 100 (50%) were in the endometriosis group and 100 (50%) in the hysterectomy group. The endometriosis group was characterized by younger age and lower parity (both, p<0.001). There was no significant difference between the groups in mean VAS scores for each post-operative day. However, among patients who needed additional analgesics beyond the standard protocol on POD 1, a higher percentage of women in the endometriosis group used opioids rather than milder analgesics, as compared to controls (1% vs. 0.2%, respectively, p = 0.03). CONCLUSION: Increased post-operative morphine use was observed in patients with endometriosis following laparoscopic surgery, despite no significant difference in mean VAS scores during the post-operative days. These findings suggest that personalized pain relief protocols should be adjusted for women with endometriosis.

Clonidine as Monotherapy for Neonatal Opioid Withdrawal Syndrome: A Randomized Trial.

OBJECTIVE: We sought to determine whether clonidine, a non-opioid α-2-adrenergic agonist, would effectively treat neonatal opioid withdrawal syndrome (NOWS). METHODS: This was an intention-to-treat randomized clinical trial. Enrollment criteria included prenatal opioid exposure, age ≤7 days, gestational age ≥35 weeks, no other medical condition, and need for pharmacotherapy. Primary outcomes were length of treatment and neurobehavioral performance. RESULTS: A total of 1107 patients were screened for enrollment (645 ineligible, 91 parents or staff unavailable, 216 declined, 155 consented). Of 155 infants, 120 required treatment and were randomized to receive oral clonidine (n = 60) at 1 µg/kg/dose or morphine (n = 60), 0.06 mg/kg/dose, every 3 hours. Infants with no improvement had their doses increased by 25% of the initial dose every 12 to 24 hours. Those without improvement by the fourth dose increase, received adjunct therapy. Length of treatment did not differ between morphine and clonidine, with median (95% confidence interval [CI]) days, respectively, of 15 (13-17) and 17 (15-19), P = .48. More clonidine-treated infants (45%) needed adjunct therapy versus 10% in the morphine group, adjusted odds ratio (95% CI) = 8.85 (2.87-27.31). After treatment completion, the NICU Network Neurobehavioral Scales summary scores did not differ between clonidine-treated and morphine-treated infants. CONCLUSIONS: Length of pharmacologic treatment and final neurobehavioral performance were not significantly different between the clonidine- and morphine-treated groups. Clonidine appears to be an effective non-opioid medication to treat NOWS. Future studies are needed to determine the optimal clonidine dosage for a quicker response and obviation of adjunct therapy.

The analgesic benefit of rectus sheath block in robotic gynecologic surgery: A retrospective study.

With the growing adoption of robotic techniques in gynecologic surgery, the advantages of minimally invasive procedures over traditional open surgery, such as reduced postoperative pain and quicker recovery, are clear. Yet, establishing an effective multimodal analgesic regimen remains a challenge. This retrospective study from a tertiary care center aimed to assess the analgesic efficacy of the rectus sheath block (RSB) on postoperative pain and opioid consumption after robotic gynecologic surgery. Between June 2022 and March 2023, 20 patients who underwent robotic gynecologic surgery were evaluated. Key parameters included postoperative visual analog scale scores, opioid consumption, and postoperative nausea/vomiting instances. Anesthesia protocols were standardized, with postsurgical pain management involving RSB and a patient-controlled analgesia device filled with morphine. Patients showed an average morphine intake of 8.2 ±â€…5.09 mg over the initial 24 hours postsurgery. During mobilization, average pain scores were consistently low, with no correlation identified between opioid consumption and age or body mass index. 40% of patients reported postoperative nausea on the first day, and no complications linked to the RSB were observed. The study underlines the potential of integrating RSB in a multimodal analgesic regimen after robotic gynecologic surgery. Its application may lead to reduced opioid consumption and more efficient postoperative pain management. Further randomized controlled trials are recommended to validate these findings.

Bilateral Ultrasound-Guided External Oblique Intercostal Block Vs. Modified Thoracoabdominal Nerve Block Through Perichondrial Approach for Postoperative Analgesia in Patients Undergoing Laparoscopic Sleeve Gastrectomy Surgery: A Randomized Controlled Study.

INTRODUCTION: The objective of the present study was to evaluate morphine consumption and pain scores 24 h postoperatively to compare the effects of a bilateral External Oblique Intercostal (EOI) block with those of a Modified Thoracoabdominal Nerve Block Trough Perichondrial Approach (M-TAPA) block in laparoscopic sleeve gastrectomy (LSG). METHODS: Fifty-eight patients aged between 18 and 65 years of with American Society of Anesthesiologists class II-III were included in this randomized, double-blinded study. Patients were assigned into two groups either EOI block or M-TAPA block. The primary outcome was cumulative morphine consumption within the first postoperative 24 h. Secondary outcomes were numerical rating scale (NRS) scores at rest and during activity, QoR-15 Patient Questionnaire scores, incidence of postoperative nausea and vomiting (PONV), number of patients requiring rescue analgesic and antiemetics drugs, and complications. RESULTS: There was no statistically significant difference between the groups in terms of morphine consumption in the first 24 h (EOI block; 10.74 ± 3.94 mg vs. M-TAPA block; 11.67 ± 4.66 mg, respectively). In addition, no significant difference between the two groups in the NRS and PONV scores, total QoR-15 scores, and the number of patients requiring rescue analgesics and antiemetics. CONCLUSIONS: EOI block and M-TAPA block showed similar effectiveness for morphine consumption within 24 h postoperatively and in pain scores in LSG.

Intrathecal Morphine Enhances Postoperative Analgesia and Recovery in Robotic-Assisted Laparoscopic Partial Nephrectomy: A Retrospective Study of 272 Patients.

BACKGROUND Robot-assisted laparoscopic partial nephrectomy (RAPN) has been increasingly used for treating renal tumors due to its advantages over other approaches. However, RAPN can induce acute incisional, peritoneal, visceral, and referred pain. Therefore, acute pain control in robotic surgery is a concern. This retrospective study aimed to evaluate the efficacy of intrathecal morphine (ITM) for postoperative analgesia and recovery after RAPN. MATERIAL AND METHODS We retrospectively investigated consecutive patients who underwent RAPN at our institute between 2020 and 2021. Among the 272 patients who met the inclusion criteria, 135 patients were administered 200 µg of ITM preoperatively (ITM group), while 137 patients were not (control group). Postoperative pain assessments using the numeric rating scale (NRS), opioid requirements, and recovery profiles during the first postoperative 24 h were compared between the 2 groups. RESULTS As the primary endpoint, the incidence of moderate-to-severe pain (24-h average NRS pain score ≥4) was significantly lower in the ITM group than in the control group (36.3% vs 61.3%, P<0.001). Pain scores and cumulative opioid requirements were also significantly lower in the ITM group for all assessments (P<0.001). Moreover, the ITM group had a higher score on the Quality of Recovery-15 questionnaire on the first postoperative day (129 vs 120, P=0.003) despite an increased rate of postoperative nausea/vomiting (27.4% vs 13.1%, P=0.003). CONCLUSIONS Our findings indicate that ITM provided superior pain control during the early period following RAPN, with reduced postoperative opioid requirements. Moreover, ITM improved patient satisfaction with recovery.

3,3-Dibromoflavanone, a synthetic flavonoid derivative for pain management with antidepressant-like effects and fewer side effects than those of morphine in mice.

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

TMEM132C rs7296262 Single-Nucleotide Polymorphism Is Significantly Associated with Nausea Induced by Opioids Administered for Cancer Pain and Postoperative Pain.

Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the TMEM132C rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, p = 0.0001; CIH group, p = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the TMEM132C rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Low-dose ketamine as an adjunct to morphine: A randomized controlled trial among patients with and without current opioid use.

BACKGROUND: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low-dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use. METHODS: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0-10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction. RESULTS: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5-67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3-6]) compared to the placebo group (1 [IQR 0-2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min. CONCLUSIONS: LDK may be effective as an adjunct analgesic to morphine for short-term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use.

Intravenous Methadone versus Intrathecal Morphine as Part of an Enhanced Recovery After Cardiac Surgery Protocol on Postoperative Pain and Outcomes: A Retrospective Cohort Study.

OBJECTIVES: Evaluate the effect of intravenous (IV) methadone versus intrathecal morphine (ITM) within an Enhanced Recovery After Cardiac Surgery (ERACS) pathway on postoperative pain and outcomes (length of hospital stay and postoperative complications) after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Two tertiary academic medical institutions within the same health system. PARTICIPANTS: Eligible 289 adult patients undergoing elective cardiac surgery with an enhanced recovery pathway from January 2020 through July 2021. INTERVENTIONS: Patients were administered ITM (0.25 mg) or IV methadone (0.1 mg/kg) if ITM was contraindicated. All patients were enrolled in an ERACS pathway using current Enhanced Recovery After Surgery society guidelines. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures included postoperative pain scores and opioid consumption measured as oral morphine equivalents. We analyzed patient demographics, procedural factors, intraoperative medications, and outcomes. Adjusted linear mixed models were fit to analyze associations between intervention and pain outcomes. ITM was associated with decrease in pain scores on postoperative day 0 after adjusting for clinical variables (average marginal effect, 0.49; 95% confidence interval, 0.002-0.977; p = 0.049). No difference in opioid consumption could be demonstrated between groups after adjusting for postoperative day and other variables of interest. CONCLUSIONS: ITM when compared with IV methadone was associated with a decrease in pain scores without any difference in opioid consumption after elective cardiac surgery. Methadone can be considered as a safe and effective alternative to ITM for ERACS protocols. Future large prospective studies are needed to validate this finding and further improve analgesia and safety.

Clinical Analysis of Different Anesthesia and Analgesia Methods for Patients Undergoing Uniportal Video-assisted Lung Surgery.

PURPOSE: The purpose of this study was to compare 3 intraoperative modalities to determine the best and most convenient one for pain control for uniportal lung surgery. This study compared general anesthesia with serratus plane block, general anesthesia with epidural, and general anesthesia alone to examine postoperative pain scores in patients. METHODS: Eighty patients were enrolled and statistically analyzed. Three interventions were studied: general anesthesia with serratus plane block (group S), general anesthesia with thoracic epidural (group E), and general anesthesia only (group G). Outcome measures compared among the 3 groups included demographic characteristics; surgical types; anesthesia and operative time; postoperative pain scores; vital signs; morphine consumption at 0, 2, and 6 hours and day 1 and day 2 after surgery; incidence of opioid-related adverse events and chronic pain; hospital length of stay (LOS); and overall expenses. The numerical rating scale was used to assess the degree of pain on the first and second postoperative days. Postoperative morphine consumption, incidence of opioid-related side effects, hospital LOS, and overall hospital expenses were documented, as well as incidence of chronic postoperative pain. FINDINGS: There was no difference in the incidence of opioid-related adverse events and chronic pain, hospital LOS, and overall expenses among the 3 groups. After investigating factors that may influence hospital LOS and overall expenses, the multivariable analysis indicated that only longer operative time was associated with longer hospital stay and more hospital expenses. IMPLICATIONS: This prospective study found that general anesthesia alone offers an easy and efficient approach resulting in similar postoperative pain scores and morphine consumption compared with nerve block and epidural. Longer operative time was associated with longer hospital stay and more hospital expenses. CLINICALTRIALS: gov identifier: NCT03839160. (Clin Ther. 2024;XX:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Efficacy and Safety of Intrathecal Morphine for Cesarean Delivery: A Narrative Review.

PURPOSE OF REVIEW: Pain management is a critical aspect of care during and following a cesarean delivery. Without proper control of pain, individuals can experience poor mobility, increased thromboembolic events, and difficulty caring for the neonate in the postpartum period. There have been multiple methods for pain management for cesarean delivery and intrathecal morphine (ITM) has emerged as a prominent option for post-operative analgesia due to its efficacy, safety, and potential benefits over other treatments. This review analyzes data on efficacy, side effects, and safety of ITM and the pain control alternatives. RECENT FINDINGS: A comprehensive literature review was conducted to compare ITM with other analgesic techniques in post-cesarean patients. ITM was found to be as effective or better than other analgesic options, including bilateral quadratus lumborum block (QLB), opioid-free epidural analgesia (CSEA-EDA), and intravenous fentanyl. One study found that both ITM and oral analgesia were effective in pain control and that ITM caused fewer breakthrough pain events but had a longer duration and a greater rate of side effects than oral opioid analgesia. Commonly observed side effects of intrathecal opioids include nausea, vomiting, pruritus, and urinary retention, and it is thought that the adverse effects from intrathecal administration of opioids are short-lived. ITM may provide a decreased risk of DVT and coagulation by decreasing lower extremity weakness and numbness, thereby decreasing recovery time and increasing mobility. ITM is a safe and effective option for post-cesarean analgesia, with comparable pain relief to alternative forms of pain control, and side effects that are generally manageable. Further research is warranted to explore beneficial combinations with other methods of pain management and optimal dosing strategies.

Anterior quadratus lumborum block provided superior pain control and reduced opioid consumption in kidney transplantation: A randomized controlled trial.

BACKGROUND: The research aimed to assess the effectiveness of inside-out anterior quadratus lumborum (QL3) block and local wound infiltration in managing postoperative pain and total morphine dosage following kidney transplantation. METHODS: In this prospective, randomized, double-blind study; 46 end-stage renal disease patients undergoing kidney transplantation were randomly allocated into 2 groups: a QL group (n = 23) receiving 20 mL of 0.25% bupivacaine using the ultrasound-assisted inside-out technique before wound closure, while the local wound infiltration (LA) group (n = 23) receiving the same dose around the surgical wound and drain at the time of skin closure. The primary outcome measure was the numerical pain rating scale, with secondary outcomes including amount of morphine consumption at various postoperative time points (2nd, 4th, 6th, 12th, 18th and 24th hours). RESULTS: Patients in the QL group had significantly lower numerical rating scale scores at the 2nd and 4th hours, both at rest and during movement (P < .05). Although pain scores at rest and during movement at later time points were lower in the QL group compared to the LA group, these differences were not statistically significant. Cumulative morphine consumption at postoperative 4th, 6th, 12th, 18th and 24th hours was significantly lower in the QL group (P < .05). No patients experienced complications from the QL3 block. CONCLUSION: Ultrasound-assisted inside-out QL3 block significantly reduced postoperative pain levels at the 2nd and 4th hours, both at rest and during movement, and led to a reduction in cumulative morphine consumption from the 4th hour postoperatively, and persisting throughout the 24-hour period.

EASIER trial (Erector-spinAe analgeSia for hepatopancreaticobiliary pain In the Emergency Room): a single-centre open-label cohort-based randomised controlled trial analysing the efficacy of the ultrasound-guided erector-spinae plane block compared with intravenous morphine in the treatment of acute hepatopancreaticobiliary pain in the emergency department.

BACKGROUND: Ultrasound-guided (USG) erector-spinae plane block (ESPB) may be better than intravenous opioids in treating acute hepatopancreaticobiliary (HPB) pain in the ED. METHODS: This open-label randomised controlled trial was conducted in the ED of a tertiary-care hospital between March and August 2023. All adult patients with severe HPB pain were recruited during times that a primary investigator was present. Unconsenting patients, numeric rating scale (NRS) ≤6, age ≤18 and ≥80 years, pregnant, unstable or with allergies to local anaesthetics or opioids were excluded. Patients in the intervention arm received bilateral USG ESPB with 0.2% ropivacaine at T7 level, by a trained ED consultant, and those in the control arm received 0.1 mg/kg intravenous morphine. Pain on a 10-point NRS was assessed by the investigators at presentation and at 1, 3, 5 and 10 hours after intervention by the treatment team, along with rescue analgesia requirements and patient satisfaction. Difference in NRS was analysed using analysis of co-variance (ANCOVA) and t-tests. RESULTS: 70 participants were enrolled, 35 in each arm. Mean age was 40.4±13.2 years, mean NRS at presentation in the intervention arm was 8.0±0.9 and 7.6±0.6 in the control arm. NRS at 1 hour was significantly lower in the ESPB group (ANCOVA p<0.001). At 1, 3, 5 and 10 hours, reduction of NRS in the intervention arm (7±1.6, 6.7±1.9, 6.6±1.8, 6.1±1.9) was significantly greater than the control arm (4.4±2, 4.6±1.8, 3.7±2.2, 3.8±1.8) (t-test, p<0.001). Fewer patients receiving ESPB required rescue analgesia at 5 (t-test, p=0.031) and 10 hours (t-test, p=0.04). More patients were 'very satisfied' with ESPB compared with receiving only morphine at each time period (p<0.001). CONCLUSION: ESPB is a promising alternative to morphine in those with HPB pain. TRIAL REGISTRATION NUMBER: CTRI/2023/03/050595.

Fracture pain in children in the emergency department: the impact of a new pain management procedure.

PURPOSE: To compare compliance with the French national guidelines before and after the implementation (in 2018) of a new protocol on acute fracture pain management in the pediatric emergency department of a French university medical center. METHODS: We conducted a retrospective, before-after study in patients aged below 16 years presenting at the pediatric emergency department with a fracture. We compared pain management before (in 2017) and after (in 2019 and 2020) implementation of the new procedure. The primary endpoint was appropriate pain management, defined as (i) an appropriate initial assessment of pain, (ii) appropriate treatment with analgesic drugs (acetaminophen for mild pain, acetaminophen and ibuprofen for moderate pain, ibuprofen and morphine for severe pain) and (iii) reassessment of the pain intensity. RESULTS: 572 patients were included (mean age: 6.5 years; male: 60%). 190 in 2017 and 382 in 2019-2020. Pain management was appropriate for 40% of the patients in 2017 and 52% in 2019-2020 (p = 0.004). Pain was rated for 98% of patients in 2017 vs. 100% in 2019-2020 (p = 0.04). The frequency of appropriate treatment for mild pain and moderate pain increased significantly from 52 to 76% and from 0 to 44%, respectively. The administration of ibuprofen increased by 26% points (from 3 to 20 patients treated) and the administration of morphine increased by 29% points (from 1 to 17 patients treated). Pain reassessment rose significantly from 21 to 43%. Levels of compliance with the guidelines were similar in 2019 and 2020. Analgesia was significantly more effective in 2019-2020 than in 2017 (in 20% vs. 14% of the patients, respectively; p = 0.005). CONCLUSION: After the implementation of a new protocol for the management of acute fracture pain, we observed an increase in compliance with the guidelines. Although the use of ibuprofen and morphine rose significantly as did the frequency of pain reassessment, further improvements are required.

A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model.

The ligands of chemokine receptors 2 and 5 (CCR2 and CCR5, respectively) are associated with the pathomechanism of neuropathic pain development, but their role in painful diabetic neuropathy remains unclear. Therefore, the aim of our study was to examine the function of these factors in the hypersensitivity accompanying diabetes. Additionally, we analyzed the analgesic effect of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, and its influence on the effectiveness of morphine. An increasing number of experimental studies have shown that targeting more than one molecular target is advantageous compared with the coadministration of individual pharmacophores in terms of their analgesic effect. The advantage of using bifunctional compounds is that they gain simultaneous access to two receptors at the same dose, positively affecting their pharmacokinetics and pharmacodynamics and consequently leading to improved analgesia. Experiments were performed on male and female Swiss albino mice with a streptozotocin (STZ, 200 mg/kg, i.p.) model of diabetic neuropathy. We found that the blood glucose level increased, and the mechanical and thermal hypersensitivity developed on the 7th day after STZ administration. In male mice, we observed increased mRNA levels of Ccl2, Ccl5, and Ccl7, while in female mice, we observed additional increases in Ccl8 and Ccl12 levels. We have demonstrated for the first time that a single administration of cenicriviroc relieves pain to a similar extent in male and female mice. Moreover, repeated coadministration of cenicriviroc with morphine delays the development of opioid tolerance, while the best and longest-lasting analgesic effect is achieved by repeated administration of cenicriviroc alone, which reduces pain hypersensitivity in STZ-exposed mice, and unlike morphine, no tolerance to the analgesic effects of CVC is observed until Day 15 of treatment. Based on these results, we suggest that targeting CCR2 and CCR5 with CVC is a potent therapeutic option for novel pain treatments in diabetic neuropathy patients.

Real-time and video-recorded pain assessment in beef cattle: clinical application and reliability in young, adult bulls undergoing surgical castration.

Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of real-time and video-recorded pain assessment, and their agreement, in young, adult bulls undergoing surgical castration. Ten Nelore and nine Angus bulls underwent general anesthesia and surgical castration. Three-minute real-time observations and simultaneous videos were recorded at - 48 h (M0), before sedation, under fasting (M1), after surgery, 3 h after sternal recumbency (M2), after rescue analgesia (M3) and at 24 h (M4). Animals received morphine (after M2), dipyrone (after M3), and flunixin meglumine after surgical castration (M4). Two trained evaluators assessed real-time (n = 95) and video-recorded time-points (n = 95) using the Unesp-Botucatu Cattle Pain Scale (UCAPS). Both assessment methods inferred 'very good' reliability (≥ 0.81) with minimal bias, however, video-recorded assessment (4.33 ± 2.84) demonstrated slightly higher scores compared to real-time (3.08 ± 2.84). The results from this study suggest that UCAPS can be used in real-time or video-recorded to assess pain and guide analgesic therapy in cattle.