Effects of anterior quadratus lumborum block versus erector spinae plane block on postoperative acute pain in percutaneous nephrolithotomy: a prospective, observational study.

BACKGROUND: The study aimed to compare the pain-relieving effectiveness of anterior quadratus lumborum block (QLB3) and erector spinae plane block (ESPB), both of which have been documented to provide relief during abdominal surgery. METHODS: This prospective observational study, conducted between February and July 2023, included 96 patients who had undergone percutaneous nephrolithotomy (PCNL). Patients were divided into three groups: QLB3, ESPB, and control (no block) and received the corresponding nerve block in the preanesthetic room for regional block. Cumulative morphine consumption during the initial 24 h after PCNL, numerical rating scale resting/movement scores, intraoperative remifentanil usage, rescue analgesic requirements, time when the first analgesic was requested, and postoperative nausea and vomiting scores were documented and compared between the groups. RESULTS: Total median morphine consumption in the first 24 h postoperatively was similar in the QLB3 and ESPB groups but higher in the control group (QLB3, 7 mg [(Q1-Q3) 7-8.5]; ESPB, 8 mg [6.5-9]; control, 12.5 [10-17]; P < 0.001). Similarly, median intraoperative remifentanil consumption did not differ between the block groups but was higher in the control group (QLB3, 1082 µg [IQR 805.5-1292.7]; ESPB, 1278 µg [940.2-1297.5]; control, 1561 µg [1315-2068]; P < 0.001). The number of patients receiving rescue analgesic medication was similar in the block groups but higher in the control group (QLB3, n = 9 [30%]; ESPB, n = 14 [46.7%]; control, n = 21 [70%]; P = 0.008). CONCLUSIONS: QLB3 and ESPB were adequate and comparable in providing postoperative analgesia as part of multimodal analgesia after PCNL. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (Identifier: NCT05822492).

The role of cytokines in acute and chronic postsurgical pain after major musculoskeletal surgeries in a quaternary pediatric center.

STUDY OBJECTIVE: To determine if baseline cytokines/chemokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery. DESIGN: Prospective, observational, longitudinal nested study. SETTING: University-affiliated quaternary children's hospital. PATIENTS: Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure. MEASUREMENTS: Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score > 3/10 beyond 3 months post-surgery) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes. MAIN RESULTS: Analyses included 3,164 repeated measures of 16 cytokines/chemokines from 112 subjects (median age 15.3, IQR 13.5-17.0, 54.5 % female, 59.8 % pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (ß = 0.95, SE 0.31; p = 0.003), IL-1ß (ß = 0.84, SE 0.36; p = 0.02), IL-2 (ß = 0.78, SE 0.34; p = 0.03), and IL-12 p70 (ß = 0.88, SE 0.40; p = 0.03) and longitudinal postoperative elevations in GM-CSF (ß = 1.38, SE 0.57; p = 0.03), IFNγ (ß = 1.36, SE 0.6; p = 0.03), IL-1ß (ß = 1.25, SE 0.59; p = 0.03), IL-7 (ß = 1.65, SE 0.7; p = 0.02), and IL-12 p70 (ß = 1.17, SE 0.58; p = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (ß = -0.39, SE 0.17; p = 0.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (ß = -0.57, SE 0.26; p = 0.03), IL-8 (ß = -0.68, SE 0.24; p = 0.006), and IL-13 (ß = -0.48, SE 0.22; p = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively. CONCLUSION: We identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.

Video-based compilation of acute pain behaviours in cats.

OBJECTIVES: The aim of this work was to create a video-based compilation of acute pain behaviours in cats as an open-access online resource for training of veterinary health professionals. METHODS: A database comprising 60 h of video recordings of cats was used. Videos were previously recorded after ethical approval and written client consent forms, and involved cats with different types (eg, medical, surgical, trauma, orofacial) and degrees (eg, from no pain to severe pain) of acute pain, before and after surgery or the administration of analgesia. The database included videos of cats of different coat colours, ages, sex and breeds. Video selection was based on a published ethogram of acute pain behaviours in cats. Videos were selected by one observer (SM) according to their definition and quality, followed by a second round of screening by two observers (SM and PVS). Video editing included a standardised template (ie, watermark and titles). RESULTS: A total of 24 videos (mean length 33 ± 17 s) with each acute pain-related behaviour described in the ethogram were uploaded to an open-access online video-sharing platform (http://www.youtube.com/@Steagalllaboratory) with an individual hyperlink. Videos were provided with a short description of the behaviour for the public. CONCLUSIONS AND RELEVANCE: This video-based compilation may promote better training of veterinary health professionals on acute pain assessment while improving feline health and welfare and the understanding of cat behaviours.

Conservative Treatments in the Management of Acute Painful Vertebral Compression Fractures: A Systematic Review and Network Meta-Analysis.

Importance: Osteoporotic vertebral compression fractures (VCFs) frequently cause substantial pain and reduced mobility, posing a major health problem. Despite the critical need for effective pain management to restore functionality and improve patient outcomes, the value of various conservative treatments for acute VCF has not been systematically investigated. Objective: To assess and compare different conservative treatment options in managing acute pain related to VCF. Data Sources: On May 16, 2023, 4 databases-PubMed, Embase, Scopus, and CINAHL-were searched. In addition, a gray literature search within Scopus and Embase was also conducted. Study Selection: Included studies were prospective comparative and randomized clinical trials that assessed conservative treatments for acute VCF. Data Extraction and Synthesis: Data extraction and synthesis were performed by 2 authors according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analyses recommendations. A frequentist graph-theoretical model and a random-effects model were applied for the meta-analysis. Main Outcomes and Measures: Primary outcomes were short-term (4 weeks) pain during activity and long-term (latest available follow-up) nonspecified pain in patients with acute VCF. Results: The study included 20 trials, encompassing 2102 patients, and evaluated various interventions for managing VCF. Calcitonin (standardized mean difference [SMD], -4.86; 95% CI, -6.87 to -2.86) and nonsteroidal anti-inflammatory drugs (NSAIDs; SMD, -3.94; 95% CI, -7.30 to -0.58) were beneficial regarding short-term pain during activity compared with placebo. For long-term nonspecific pain management, bisphosphonates were associated with inferior pain outcomes compared with daily (SMD, 1.21; 95% CI, 0.11 to 2.31) or weekly (SMD, 1.13; 95% CI, 0.05 to 2.21) administration of teriparatide, with no treatment being superior to NSAIDs. The qualitative analysis of adverse events highlighted that typical adverse events associated with these medications were observed. Conclusions and Relevance: NSAIDs and teriparatide may be the preferred treatment options for pain management in acute osteoporotic VCF. Although calcitonin also proved to be beneficial, its safety profile and potential adverse effects restrict its widespread application. The limited evidence on braces and analgesics underscores the urgent need for future research.

Less experienced observers assess piglet castration-induced acute pain differently than experienced observers: A pilot study.

Behavioral pain scales have been helpful for standardized swine pain assessment. However, it is still unknown if observers' experience influences the scale score. We conducted a pilot study to investigate how three different levels of swine experience influenced how observers scored castration pain in piglets using Unesp-Botucatu Pig Composite Acute Pain Scale (UPAPS). We used a database from UPAPS scores from pigs undergoing surgical castration in a previous study. Scores were attributed by six observers with Little to no experience (n = 2), Some experience (n = 2) and Extensive experience (n = 2). Reliability was estimated using the intraclass correlation coefficient, agreement was investigated by Bland-Altman analysis, predictive capacity was estimated using the area under the curve (AUC), and statistical differences were tested using a regression model. We found that intra-experience levels reliability were satisfactory (Little to no: 0.72, Some: 0.81, Extensive: 0.84), but inter-experience reliability was lower (0.42). Little to no experience observers had poor agreement with other observers, with a bias toward underscoring UPAPS (bias of 0.94 vs. Some, 1.17 vs. Extensive). Predictive capacity was similar between all observers (AUC, Little to no: 71.94%, Some: 76.10%, Extensive: 79.09%, p > 0.05). Regression model confirmed underscoring of Little to no experience observers (mean ± standard error; Little to no: 1.09 ± 0.14; Some: 2.02 ± 0.23; Extensive: 2.25 ± 0.22; p < 0.05). We concluded that minimal experience, as Some experience observers have in the swine industry, is sufficient for them to score UPAPS in a similar way than more experienced observers. The present pilot study supports the enhancement and implementation of UPAPS on farm and laboratory settings by minimally qualified observers, improving swine welfare in the short and long term.

Acute and persistent post-operative pain following mastectomy: a descriptive study in a tertiary hospital cohort.

AIMS: Post mastectomy pain syndrome (PMPS) can have significant negative effects on patients' quality of life after mastectomy. The estimated prevalence of PMPS varies widely and there is little data from a New Zealand population. This limits clinicians' ability to meaningfully describe and discuss pain-related complications of mastectomy peri-operatively. METHOD: We designed a single-centre, retrospective study to describe acute post-operative analgesic requirements after mastectomy, to describe the prevalence of PMPS at least 1 year after surgery, and to identify associated risk factors for this complication. RESULTS: One hundred and thirty mastectomy patients met inclusion criteria and 59 were willing and able to participate in 12-month follow-up. Acute post-operative pain was generally well managed with modest doses of oral analgesics. Sixty-six percent (n=39) of women reported some form of persistent pain symptoms post-mastectomy; this was associated with younger age, axillary surgery and chemotherapy. Only 5% of patients (n=3) met consensus criteria for PMPS, which limited identification of risk factors for this more severe complication. CONCLUSION: Despite PMPS occurring infrequently, post-operative pain of a less severe nature after mastectomy occurs commonly. Clinicians should remain vigilant to possible risk factors for this post-operative complication and counsel patients appropriately.

Depolarization of mouse DRG neurons by GABA does not translate into acute pain or hyperalgesia in healthy human volunteers.

The majority of somatosensory DRG neurons express GABAA receptors (GABAAR) and depolarise in response to its activation based on the high intracellular chloride concentration maintained by the Na-K-Cl cotransporter type 1 (NKCC1). The translation of this response to peripheral nerve terminals in people is so far unclear. We show here that GABA (EC50 = 16.67µM) acting via GABAAR produces an influx of extracellular calcium in approximately 20% (336/1720) of isolated mouse DRG neurons. In contrast, upon injection into forearm skin of healthy volunteers GABA (1mM, 100µl) did not induce any overt sensations nor a specific flare response and did not sensitize C-nociceptors to slow depolarizing electrical sinusoidal stimuli. Block of the inward chloride transporter NKCC1 by furosemide (1mg/100µl) did not reduce electrically evoked pain ratings nor did repetitive GABA stimulation in combination with an inhibited NKCC1 driven chloride replenishment by furosemide. Finally, we generated a sustained period of C-fiber firing by iontophoretically delivering codeine or histamine to induce tonic itch. Neither the intensity nor the duration of histamine or codeine itch was affected by prior injection of furosemide. We conclude that although GABA can evoke calcium transients in a proportion of isolated mouse DRG neurons, it does not induce or modify pain or itch ratings in healthy human skin even when chloride gradients are altered by inhibition of the sodium coupled NKCC1 transporter.

Implementation of the WHO standards to assess quality of care for children with acute pain in EDs: findings of a multicentre study (CHOICE) in Italy.

BACKGROUND: There is little experience on the use of the WHO Standards for improving the quality of care (QOC) for children. We describe the use of four prioritised WHO Standard-based Quality Measures to assess the provision of care for children with pain in emergency departments (EDs). METHODS: In a multicentre observational study in 10 EDs with different characteristics in Italy, we collected data on 3355 children accessing the EDs between January 2019 and December 2020. The association between children and facility characteristics and quality measures was analysed through multivariate analyses. RESULTS: The proportion of children whose pain was measured was 68.7% (n=2305), with extreme variations across different centres (from 0.0% to 99.8%, p<0.001). The proportion of children treated for pain was 28.9% (n=970) again with a wide range (5.3%-56.3%, p<0.001). The difference between the frequency of children with pain measured and pain treated varied widely between the facilities (ranging from -24.3 to 82). Children with moderate and severe pain were more frequently treated (48.9% and 62.9% of cases, respectively), although with large variations across centres (ranges: 0%-74.8% and 0%-100% respectively, p<0.001). After correction for children's characteristics, the variable more strongly associated with analysed outcomes was the facility which the child accessed for care. Being a facility in Northern Italy was associated with a higher rate of pain measurement (67.3%-95% CI: 39.9% to 94.6%, p<0.001) compared with facilities in South Italy (-22.1% lower (95% CI: -41.7% to -2.50%, p=0.03). CONCLUSIONS: The use of few WHO Standard-based measures related to pain can help identifying priority gaps in QOC for children and in monitoring it over time. There is a need for more implementation research to establish which are the most sustainable and effective interventions to improve the QOC for acute pain in children.

People With Acute Low Back Pain Have Concerns That May Not Be Addressed by Guideline-Recommended Advice: A Mixed-Methods Study.

OBJECTIVE: To investigate what concerns people with acute low back pain (LBP) and explore whether demographic and clinical factors were associated with having concerns about LBP. DESIGN: Mixed-methods study. METHODS: We included participants aged ≥18 years with acute LBP (LBP≤6 weeks). We collected demographic and clinical characteristics via an online survey and asked one open-ended question to elicit participants' concerns about their LBP. We investigated concerns about LBP using inductive content analysis. Using multivariable logistic regression, we explored associations between demographic and clinical characteristics and having concerns about LBP. RESULTS: We included 2025 participants, a majority of whom (n = 1200, 59.3%) reported having at least 1 concern about their LBP. There were 34 unique concerns, which mapped to 5 themes: causes of LBP (n = 393, 19.4%), future consequences of LBP (n = 390, 19.3%), psychosocial consequences of LBP (n = 287, 14.2%), physical consequences of LBP (n = 210, 10.4%), and health consequences of LBP (n = 84, 4.2%). Demographic and clinical characteristics were associated with having concerns about LBP: participants with university education, having previously received advice for LBP, with higher LBP intensity, interference, and higher anxiety symptoms were more likely to have concerns about their LBP. CONCLUSION: Most people with acute LBP had at least 1 concern about their LBP, more commonly centered around the causes of and the future consequences of LBP. J Orthop Sports Phys Ther 2024;54(9):1-9. Epub 7 August 2024. doi:10.2519/jospt.2024.12571.

Predicting risk factors for acute pain after hepatobiliary and pancreatic surgery: an observational case control study.

BACKGROUND: Inadequate postoperative analgesia is associated with increased risks of various postoperative complications, longer hospital stay, decreased quality of life and higher costs. OBJECTIVES: This study aimed to investigate the risk factors for moderate-to-severe postoperative pain within the first 24 hours and 24-48 hours after major hepatobiliary pancreatic surgery. METHODS: Data of patients who underwent surgery at the Department of Hepatobiliary Surgery in Henan Provincial People's Hospital were collected from January 2018 to August 2020. Univariate and multivariate logistic regression analyses were used to identify the risk factors of postoperative pain. RESULTS: In total, 2180 patients were included in the final analysis. 183 patients (8.4%) suffered moderate-to-severe pain within 24 hours after operation. The independent risk factors associated with moderate-to-severe pain 24 hours after procedures were younger age (OR, 0.97; 95% CI 0.95 to 0.98, p<0.001), lower body mass index (BMI) (OR, 0.94; 95% CI 0.89 to 0.98, p=0.018), open surgery (OR, 0.34; 95% CI 0.22 to 0.52, p<0.001), and postoperative analgesia protocol with sufentanil (OR, 4.38; 95% CI 3.2 to 5.99, p<0.001). Postoperative hospital stay was longer in patients with inadequate analgesia (p<0.05). CONCLUSION: Age, BMI, laparoscopic surgery, and different analgesic drugs were significant predictors of postoperative pain after major hepatobiliary and pancreatic surgery. TRIAL REGISTRATION: ChiCTR2100049726.

Current concepts and targets for preventing the transition of acute to chronic postsurgical pain.

PURPOSE OF REVIEW: It is estimated that approximately a third of patients undergoing certain surgeries may report some degree of persistent pain postoperatively. Chronic postsurgical pain (CPSP) reduces quality of life, is challenging to treat, and has significant socio-economic impact. RECENT FINDINGS: From an epidemiological perspective, factors that predispose patients to the development of CPSP may be considered in relation to the patient, the procedure or, the care environment. Prevention or management of transition from acute to chronic pain often need a multidisciplinary approach beginning early in the preoperative period and continuing beyond surgical admission. The current concepts regarding the role of central and peripheral nervous systems in chronification of pain may provide targets for future therapies but, the current evidence seems to suggest that a multimodal analgesic approach of preventive analgesia along with a continued follow-up and treatment after hospital discharge may hold the key to identify and manage the transitioning of acute to chronic pain. SUMMARY: A comprehensive multidisciplinary approach with prior identification of risk factors, minimizing the surgical insult and a culture of utilizing multimodal analgesia and continued surveillance beyond the period of hospitalization is an important step towards reducing the development of chronic pain. A transitional pain service model may accomplish many of these goals.

Prospective cohort study investigating frequency and risk factors for acute pain 1 day after refractive surgery.

BACKGROUND/AIMS: To examine demographic and clinical factors associated with ocular pain 1 day after refractive surgery. METHODS: Prospective study of individuals undergoing refractive surgery. Participants rated their ocular pain on a 0-10 numerical rating scale (NRS) presurgery and 1 day after surgery. Presurgery, participants completed questionnaires on demographics, comorbidities, medications and dry eye and ocular pain symptoms; and an anaesthetised Schirmer test was performed. Acute ocular pain 1 day after surgery was defined as an NRS score of worst pain since surgery ≥3 and this group was compared with individuals with NRS scores<3. RESULTS: 251 individuals underwent refractive surgery (89% laser-assisted in situ keratomileusis, n=222; 11% PRK, n=29). Mean age was 35±8 years (range 19 to 60); 60% (n=150) self-identified as female, 80% (n=203) as White, and 36% (n=89) as Hispanic. Thirteen (5%) individuals reported ocular pain (NRS ≥3) prior to surgery and 67% (n=168) reported ocular pain 1 day after surgery (nine individuals had pain at both time points). Factors that were associated with pain 1 day after surgery included Hispanic ethnicity (adjusted relative risk (aRR) 1.42, 95% CI 1.21 to 1.68, p<0.001) and the presence of eye pain presurgery (aRR 1.10, 95% CI 1.02 to 1.18, p=0.02). CONCLUSION: A majority of individuals report moderate or greater pain within 24 hours of refractive surgery. Hispanic ethnicity and eye pain prior to surgery were associated with self-reported acute postsurgical pain.

Opioid prescribing requirements to minimize unused medications after an emergency department visit for acute pain: a prospective cohort study.

BACKGROUND: Unused opioid prescriptions can be a driver of opioid misuse. Our objective was to determine the optimal quantity of opioids to prescribe to patients with acute pain at emergency department discharge, in order to meet their analgesic needs while limiting the amount of unused opioids. METHODS: In a prospective, multicentre cohort study, we included consecutive patients aged 18 years and older with an acute pain condition present for less than 2 weeks who were discharged from emergency department with an opioid prescription. Participants completed a pain medication diary for real-time recording of quantity, doses, and names of all analgesics consumed during a 14-day follow-up period. RESULTS: We included 2240 participants, who had a mean age of 51 years; 48% were female. Over 14 days, participants consumed a median of 5 (quartiles, 1-14) morphine 5 mg tablet equivalents, with significant variation across pain conditions (p < 0.001). Most opioid tablets prescribed (63%) were unused. To meet the opioid need of 80% of patients for 2 weeks, we found that those experiencing renal colic or abdominal pain required fewer opioid tablets (8 morphine 5 mg tablet equivalents) than patients who had fractures (24 tablets), back pain (21 tablets), neck pain (17 tablets), or other musculoskeletal pain (16 tablets). INTERPRETATION: Two-thirds of opioid tablets prescribed at emergency department discharge for acute pain were unused, whereas opioid requirements varied significantly based on the cause of acute pain. Smaller, cause-specific opioid prescriptions could provide adequate pain management while reducing the risk of opioid misuse. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03953534.

Opioid analgesic dose and route conversion ratio studies: a scoping review to inform an eDelphi guideline.

BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. CONCLUSION: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.

Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?

INTRODUCTION: Acute pain episodes, also known as vaso-occlusive crises (VOC), are a major symptom of sickle cell disease (SCD) and lead to frequent hospitalizations. The diagnosis of VOC can be challenging, particularly in adults with SCD, 50% of whom have chronic pain. Several potential biomarkers have been proposed for identifying individuals with VOC, including elevation above the baseline of various vascular growth factors, cytokines, and other markers of inflammation. However, none have been validated to date. AREAS COVERED: We summarize prospective biomarkers for the diagnosis of acute pain in SCD, and how they may be involved in the pathophysiology of a VOC. Previous and current strategies for biomarker discovery, including the use of omics techniques, are discussed. EXPERT OPINION: Implementing a multi-omics-based approach will facilitate the discovery of objective and validated biomarkers for acute pain.

Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules.

OBJECTIVE: To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules. MATERIALS AND METHODS: In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients' satisfaction. RESULTS: No significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272). CONCLUSIONS: The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.

Restraint stress-induced antinociceptive effects in acute pain: Involvement of orexinergic system in the nucleus accumbens.

The complicated relevance between stress and pain has been identified. Neurotransmitters and neuropeptides of various brain areas play a role in this communication. Pain inhibitory response is known as stress-induced analgesia (SIA). The studies demonstrated that the nucleus accumbens (NAc) is critical in modulating pain. As a neuropeptide, orexin is crucially involved in initiating behavioral and physiological responses to threatening and unfeeling stimuli. However, the role of the orexin receptors of the NAc area after exposure to restraint stress (RS) as acute physical stress in the modulation of acute pain is unclear. One hundered twenty adult male albino Wistar rats (230-250 g) were used. Animals were unilaterally implanted with cannulae above the NAc. The SB334867 and TCS OX2 29 were used as antagonists for OX1r and OX2r, respectively. Different doses of the antagonists (1, 3, 10, and 30 nmol/0.5 µl DMSO) were microinjected intra-NAc five minutes before exposure to RS (3 hours). Then, the tail-flick test as a model of acute pain was performed, and the nociceptive threshold (Tail-flick latency; TFL) was measured in 60-minute time set intervals. According to this study's findings, the antinociceptive effects of RS in the tail-flick test were blocked during intra-NAc administration of SB334867 or TCS OX2 29. The RS as acute stress increased TFL and deceased pain-like behavior responses. The 50 % effective dose values of the OX1r and OX2r antagonists were 12.82 and 21.64 nmol, respectively. The result demonstrated contribution of the OX1r into the NAc was more remarkable than that of the OX2r on antinociceptive responses induced by the RS. Besides, in the absence of RS, the TFL was attenuated. The current study's data indicated that OX1r and OX2r into the NAc induced pain modulation responses during RS in acute pain. In conclusion, the findings revealed the involvement of intra-NAc orexin receptors in improving SIA.