Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.

Background: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine. Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 µg·kg-1 (RD0.5 Group) or 1.0 µg·kg-1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 µg·kg-1·h-1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery. Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness. Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 µg·kg-1) may be a more appropriate choice. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).

Ultrasound-guided genitofemoral nerve block for femoral arterial access gain and closure: a randomized controlled trial.

OBJECTIVES: This study aimed to compare the analgesic efficacy and safety of the femoral branch block of the genitofemoral nerve (FBB) versus local infiltration anesthesia (LIA) for femoral arterial access gain and closure. METHODS: Eighty-two patients (age, 64.8 ± 10.9 years; female, 30.5%) undergoing endovascular procedures using 5-Fr femoral sheath were assigned to either FBB (n = 41) or LIA (n = 41). In both groups, 2% lidocaine HCL with 1:100,000 epinephrine was used as an anesthetic solution. Pain scores during access gain and closure were evaluated using a visual analog scale (score 0-10), patient satisfaction levels with the quality of anesthesia were scored on a 7-point Likert scale, and adverse events were recorded. RESULTS: The primary endpoint, pain scores during access closure, was significantly lower in the FBB group than in the LIA group (0.1 ± 0.37 vs 1.73 ± 0.92; p < 0.001). The FBB group also had significantly lower pain scores during access gain compared to the LIA group (0.83 ± 0.83 vs 2.78 ± 1.26; p < 0.001). There was an inverse relationship between pain scores and FBB after adjustment for age, gender, and body mass index (p < 0.001). FBB group reported significantly higher satisfaction with anesthesia quality compared to the LIA group (6.49 ± 0.64 vs 4.05 ± 1.05; p < 0.001). No complications were recognized in either group. CONCLUSIONS: Ultrasound-guided genitofemoral nerve blocks offered better acute pain relief and higher patient satisfaction than LIA during femoral arterial access gain and closure. CLINICAL RELEVANCE STATEMENT: In this prospective randomized controlled trial, ultrasound-guided genitofemoral nerve blocks offered better acute pain relief than local infiltration anesthesia, resulting in enhanced patient satisfaction. KEY POINTS: • FBB provided better pain relief during access gain and closure than LIA. • FBB offered higher patient satisfaction with the quality of anesthesia than LIA. • No anesthesia-related or access site complications were recognized in either treatment group.

Study protocol for a randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: 2 (TOPIC 2).

BACKGROUND: Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. METHODS: TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as 'worst chest pain over the last week' equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. DISCUSSION: Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. TRIAL REGISTRATION: NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.

A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2.

PURPOSE: Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. METHODS: Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. RESULTS: Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). CONCLUSIONS: The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. TRIAL REGISTRATION: Number: NCT01821833.

Adding Brief Pain Science or Ergonomics Messages to Guideline Advice Did Not Increase Feelings of Reassurance in People With Acute Low Back Pain: A Randomized Experiment.

OBJECTIVE: To investigate the effects of adding pain science or ergonomics messages to guideline advice on feelings of reassurance and management intentions among people with acute low back pain (LBP). DESIGN: Three-arm parallel-group randomized experiment. METHODS: We recruited people with acute LBP (pain for ≤6 weeks) to participate in an online experiment. Participants were randomized at a 1:1:1 ratio to one of three groups: guideline advice alone or guideline advice with the addition of brief pain science or ergonomics messages. The intervention was delivered via prerecorded videos in all 3 groups. Coprimary outcomes were reassurance that (1) no serious condition is causing LBP and (2) continuing with daily activities is safe. Secondary outcomes were perceived risk of developing chronic pain, management intentions (bed rest, see a health professional, see a specialist, and imaging), credibility, and relevance of the advice in addressing the participant's concerns. RESULTS: Two thousand two hundred ninety-seven responses (99.3% of 2,313 randomized) were analyzed. Adding brief pain science or ergonomics messages to guideline advice did not change reassurance that LBP was not caused by serious disease. The addition of ergonomics advice provided worse reassurance that it is safe to continue with daily activities compared to guideline advice (mean difference [MD], -0.33; 95% CI: 0.13, 0.53). There was no difference between groups on management intentions. CONCLUSION: Adding pain science or ergonomics messages to guideline advice did not increase reassurance or change management intentions in people with acute LBP. Ergonomics messages may lead to reduced feelings of reassurance. J Orthop Sports Phys Ther 2023;53(12)1-11. Epub 26 September 2023. doi:10.2519/jospt.2023.12090.

Comparison of the effects of one-level and bi-level pre-incisional erector spinae plane block on postoperative acute pain in video-assisted thoracoscopic surgery; a prospective, randomized, double-blind trial.

BACKGROUND: This prospective, randomized, double-blind trial aimed to compare the postoperative analgesic efficacy of One-Level pre-incisional erector spinae plane block (ESPB) and Bi-Level pre-incisional ESPB in patients undergoing video-assisted thoracic surgery (VATS). METHODS: This pilot trial was conducted between April 2022 and February 2023 with sixty patients. The patients were randomly divided into two groups. In One-Level ESPB Group (n = 30) block was performed at the thoracal(T)5 level with the 30 ml 0.25% bupivacaine. In the Bi-Level ESPB Group (n = 30) block was performed at T4 and T6 levels by using 15 ml of 0.25% bupivacaine for each level. In the postoperative period, 50 mg dexketoprofen every 12 h and 1 g paracetamol every 8 h were given intravenously (IV). Patient-controlled analgesia (PCA) prepared with morphine was applied to the patients. 0.5 mg/kg of tramadol was administered via IV for rescue analgesia. Visual analog scale (VAS) scores were recorded in the postoperative 1st, 2nd, 4th, 12th, 24th, and 48th -hours. The need for additional analgesics and side effects were recorded. In two groups, patients' demographics and postoperative hemodynamic data were recorded. RESULTS: VAS scores at resting were statistically significantly higher at the 1st (p: 0.002) and 4th -hour (p: 0.001) in the One-Level ESPB. When the groups were evaluated in terms of VAS coughing scores, the 4th -hour (p: 0.001) VAS coughing scores results were found to be statistically significantly higher in the One-Level ESPB group. In terms of VAS values evaluated during follow-up, the rates of VAS coughing score > 3 values were found to be statistically significantly lower in the Bi-Level ESPB group (p: 0.011). There was no statistically significant difference between the groups in terms of side effects, morphine consumption, and additional analgesic use (p > 0.05). CONCLUSIONS: Adequate analgesia was achieved in the early postoperative period in the group treated with Bi-Level ESPB with similar morphine consumption and side effects. This may be an advantage, especially in the early postoperative period when the pain is quite intense.

The efficacy of prophylactic metoclopramide in preventing nausea and vomiting in patients with acute pain treated with intravenous tramadol: a randomized double-blinded, placebo-controlled trial.

OBJECTIVE: To examine the clinical efficacy of prophylactic metoclopramide in reducing the incidence of nausea and vomiting in emergency department (ED) patients with acute pain who were treated with intravenous tramadol. RESULTS: We conducted a single-center randomized, double-blinded, placebo-controlled trial. A total of 99 ED patients presented with acute pain were recruited. Sixty-four patients were randomized, 31 patients in the treatment arm and 33 in the control arm. Overall, there were no significant differences in baseline characteristics between treatment arm and control arm. Only one patient within each arm reported having nausea symptom. No patients reported vomiting episode. There was no statistically significant difference in the proportion of patients with nausea or vomiting symptoms between the two groups (3.2% in the treatment arm vs. 3.0% in the control arm, p = 1.000). The administration of prophylactic metoclopramide may not provide additional benefit in reducing the occurrence of nausea and/or vomiting episode in ED patients with acute pain treated with intravenous tramadol. Trial registration Randomized clinical trial TCTR20220525001; registration date: 21 October 2021. Retrospectively registered.

Centers for Disease Control and Prevention Clinical Practice Guideline for Prescribing Opioids: United States, 2022: What dentists need to know.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) published the Clinical Practice Guideline for Prescribing Opioids for Pain-United States, 2022 (CDCCPG) to replace the 2016 guideline. This guideline was designed to serve as a clinical tool to improve communication between clinicians and patients and empower them to make informed, person-centered decisions regarding pain management and the prescribing of opioids. It is intended for primary care and other clinicians, including dentists, who provide pain management for adults with acute, subacute, and chronic pain. TYPES OF STUDIES REVIEWED: This article summarizes the CDCCPG, with an emphasis on information of relevance to dentistry. RESULTS: For dentists, the most important recommendations for pain management are that nonsteroidal anti-inflammatory medications are first-line medications for acute dental pain, interdisciplinary care for chronic orofacial pain is indicated, and opioids should only be prescribed for acute dental pain for a maximum of 3 days after risk assessment. PRACTICAL IMPLICATIONS: The CDCCPG contains a great deal of relevant information that can help dentists and dental specialists make safe, effective, and evidence-based decisions in providing pain control for their patients.

Use of regional analgesia to prevent the conversion from acute to chronic pain.

PURPOSE OF REVIEW: Chronic post-surgical pain (CPSP) prevalence has not changed over the past decades what questions the efficacy of preventive strategies. Regional analgesia is used to control acute pain, but preventive effect on CPSP remains debated. Failures and future application of regional analgesia to prevent transition from acute to chronic pain will be discussed. RECENT FINDINGS: After thoracotomy, perioperative regional analgesia does not seem to prevent CPSP. After breast cancer surgery, paravertebral block might prevent CPSP intensity and impact on daily life up to 12 months, particularly in high catastrophizing patients. In knee arthroplasty, perioperative regional analgesia or preoperative genicular nerve neuroablation do not prevent CPSP, although current studies present several bias. The protective role of effective regional analgesia and early pain relief in trauma patients deserves further studies. SUMMARY: Regional analgesia failure to prevent CPSP development should prompt us to reconsider its perioperative utilization. Patients' stratification, for example high-pain responders, might help to target those who will most benefit of regional analgesia. The impact of regional analgesia on secondary pain-related outcomes such as intensity and neuropathic character despite no difference on CPSP incidence requires more studies. Finally, the preventive effect of regional analgesia targeted interventions on CPSP in patients suffering from severe subacute pain deserves to be assessed.

Assessment of Intercostal Nerve Block Analgesia for Thoracic Surgery: A Systematic Review and Meta-analysis.

Importance: The use of intercostal nerve block (ICNB) analgesia with local anesthesia is common in thoracic surgery. However, the benefits and safety of ICNB among adult patients undergoing surgery is unknown. Objective: To evaluate the analgesic benefits and safety of ICNB among adults undergoing thoracic surgery. Data Sources: A systematic search was performed in Ovid MEDLINE, Ovid Embase, Scopus, and the Cochrane Library databases using terms for ICNB and thoracic surgery (including thoracic surgery, thoracoscopy, thoracotomy, nerve block, intercostal nerves). The search and results were not limited by date, with the last search conducted on July 24, 2020. Study Selection: Selected studies were experimental or observational and included adult patients undergoing cardiothoracic surgery in which ICNB was administered with local anesthesia via single injection, continuous infusion, or a combination of both techniques in at least 1 group of patients. For comparison with ICNB, studies that examined systemic analgesia and different forms of regional analgesia (such as thoracic epidural analgesia [TEA], paravertebral block [PVB], and other techniques) were included. These criteria were applied independently by 2 authors, and discrepancies were resolved by consensus. A total of 694 records were selected for screening. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data including patient characteristics, type of surgery, intervention analgesia, comparison analgesia, and primary and secondary outcomes were extracted independently by 3 authors. Synthesis was performed using a fixed-effects model. Main Outcomes and Measures: The coprimary outcomes were postoperative pain intensity (measured as the worst static or dynamic pain using a validated 10-point scale, with 0 indicating no pain and 10 indicating severe pain) and opioid consumption (measured in morphine milligram equivalents [MMEs]) at prespecified intervals (0-6 hours, 7-24 hours, 25-48 hours, 49-72 hours, and >72 hours). Clinically relevant analgesia was defined as a 1-point or greater difference in pain intensity score at any interval. Secondary outcomes included 30-day postoperative complications and pulmonary function. Results: Of 694 records screened, 608 were excluded based on prespecified exclusion criteria. The remaining 86 full-text articles were assessed for eligibility, and 20 of those articles were excluded. All of the 66 remaining studies (5184 patients; mean [SD] age, 53.9 [10.2] years; approximately 59% men and 41% women) were included in the qualitative analysis, and 59 studies (3325 patients) that provided data for at least 1 outcome were included in the quantitative meta-analysis. Experimental studies had a high risk of bias in multiple domains, including allocation concealment, blinding of participants and personnel, and blinding of outcome assessors. Marked differences (eg, crossover studies, timing of the intervention [intraoperative vs postoperative], blinding, and type of control group) were observed in the design and implementation of studies. The use of ICNB vs systemic analgesia was associated with lower static pain (0-6 hours after surgery: mean score difference, -1.40 points [95% CI, -1.46 to -1.33 points]; 7-24 hours after surgery: mean score difference, -1.27 points [95% CI, -1.40 to -1.13 points]) and lower dynamic pain (0-6 hours after surgery: mean score difference, -1.66 points [95% CI, -1.90 to -1.41 points]; 7-24 hours after surgery: mean score difference, -1.43 points [95% CI, -1.70 to -1.17 points]). Intercostal nerve block analgesia was noninferior to TEA (mean score difference in worst dynamic panic at 7-24 hours after surgery: 0.79 points; 95% CI, 0.28-1.29 points) and marginally inferior to PVB (mean score difference in worst dynamic pain at 7-24 hours after surgery: 1.29 points; 95% CI, 1.16 to 1.41 points). The largest opioid-sparing effect of ICNB vs systemic analgesia occurred at 48 hours after surgery (mean difference, -10.97 MMEs; 95% CI, -12.92 to -9.02 MMEs). The use of ICNB was associated with higher MME values compared with TEA (eg, 48 hours after surgery: mean difference, 48.31 MMEs; 95% CI, 36.11-60.52 MMEs) and PVB (eg, 48 hours after surgery: mean difference, 3.87 MMEs; 95% CI, 2.59-5.15 MMEs). Conclusions and Relevance: In this study, single-injection ICNB was associated with a reduction in pain during the first 24 hours after thoracic surgery and was clinically noninferior to TEA or PVB. Intercostal nerve block analgesia had opioid-sparing effects; however, TEA and PVB were associated with larger decreases in postoperative MMEs, suggesting that ICNB may be most beneficial for cases in which TEA and PVB are not indicated.

Acute Visceral Pain in Rats: Vagal Nerve Block Compared to Bupivacaine Administered Intramuscularly.

BACKGROUND: Visceral and parietal peritoneum layers have different sensory innervations. Most visceral peritoneum sensory information is conveyed via the vagus nerve to the nucleus of the solitary tract (NTS). We already showed in animal models that intramuscular (i.m.) injection of local anesthetics decreases acute somatic and visceral pain and general inflammation induced by aseptic peritonitis. The goal of the study was to compare the effects of parietal block, i.m. bupivacaine, and vagotomy on spinal cord and NTS stimulation induced by a chemical peritonitis. METHODS: We induced peritonitis in rats using carrageenan and measured cellular activation in spinal cord and NTS under the following conditions, that is, a parietal nerve block with bupivacaine, a chemical right vagotomy, and i.m. microspheres loaded with bupivacaine. Proto-oncogene c-Fos (c-Fos), cluster of differentiation protein 11b (CD11b), and tumor necrosis factor alpha (TNF-α) expression in cord and NTS were studied. RESULTS: c-Fos activation in the cord was inhibited by nerve block 2 hours after peritoneal insult. Vagotomy and i.m. bupivacaine similarly inhibited c-Fos activation in NTS. Forty-eight hours after peritoneal insult, the number of cells expressing CD11b significantly increased in the cord (P = .010). The median difference in the effect of peritonitis compared to control was 30 cells (CI95, 13.5-55). TNF-α colocalized with CD11b. Vagotomy inhibited this microglial activation in the NTS, but not in the cord. This activation was inhibited by i.m. bupivacaine both in cord and in NTS. The median difference in the effect of i.m. bupivacaine added to peritonitis was 29 cells (80% increase) in the cord and 18 cells (75% increase) in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli by inhibiting c-Fos and microglia activation. CONCLUSIONS: In rats receiving intraperitoneal carrageenan, i.m. bupivacaine similarly inhibited c-Fos and microglial activation both in cord and in the NTS. Vagal block inhibited activation only in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli. This emphasizes the effects of systemic local anesthetics on inflammation and visceral pain.

Raising awareness to prevent, recognise and manage acute pain during caesarean delivery: The French Practice Bulletin.

The incidence of acute pain during caesarean section varies between studies, with a reported rate ranging between 0.5%-17% for spinal anaesthesia and 1.7%-20% for epidural anaesthesia. Leaders from the French Club anesthésie-réanimation en obstétrique (CARO) convened to provide a clinical framework and practice bulletin to prevent, recognise and treat acute pain during caesarean section. First, a steering group agreed on 5 themes guiding quality of anaesthesia care for caesarean section: (1) appropriate neuraxial anaesthesia and testing of the surgical block prior to incision (PREVENTION); (2) appropriate organisation around decision to delivery time (COMMUNICATION); 3) appropriate management of pain before and/or after skin incision (RECOGNITION & RESPONSE); (4) appropriate prevention, identification and management of post-traumatic stress disorder (SCREENING, PREVENTION AND MANAGEMENT OF COMPLICATIONS); (5) management of medico-legal issues (MITIGATION). Then, an interdisciplinary multi-professional taskforce composed of obstetric anaesthesiologists, obstetricians, neonatologists, psychiatrists, midwifes, nurse anaesthetists, lawyers and patients, developed 23 statements that contribute to optimise care for caesarean section under neuraxial anaesthesia, of which 10 were deemed key recommendations. A decision-tree was built to optimise prevention, communication, recognition, response and management. The aim of this practice bulletin, which was endorsed by 6 societies, is to raise awareness on the risks associated with severe acute pain during caesarean section and to provide best clinical practices; pain during caesarean is not acceptable and should be prevented and managed by all stakeholders.

Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery.

BACKGROUND: Postoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before a painful stimulus may improve pain control. We defined pre-emptive nonsteroidal anti-inflammatories (NSAIDs) as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. OBJECTIVES: To assess the efficacy of preventive and pre-emptive NSAIDs for reducing postoperative pain in adults undergoing all types of surgery. SEARCH METHODS: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED and CINAHL (up to June 2020). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) only. We included adult participants undergoing any type of surgery. We defined pre-emptive NSAIDs as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. We included studies that gave the medication by any route but not given on the skin. DATA COLLECTION AND ANALYSIS: We used the standard methods expected by Cochrane, as well as a novel publication bias test developed by our research group. We used GRADE to assess the certainty of the evidence for each outcome. Outcomes included acute postoperative pain (minimal clinically important difference (MCID): 1.5 on a 0-10 scale), adverse events of NSAIDs, nausea and vomiting, 24-hour morphine consumption (MCID: 10 mg reduction), time to analgesic request (MCID: one hour), pruritus, sedation, patient satisfaction, chronic pain and time to first bowel movement (MCID: 12 hours). MAIN RESULTS: We included 71 RCTs. Seven studies are awaiting classification. We included 45 studies that evaluated pre-emptive NSAIDs and 26 studies that evaluated preventive NSAIDs. We considered only four studies to be at low risk of bias for most domains. The operations and NSAIDs used varied, although most studies were conducted in abdominal, orthopaedic and dental surgery. Most studies were conducted in secondary care and in low-risk participants. Common exclusions were participants on analgesic medications prior to surgery and those with chronic pain. Pre-emptive NSAIDs compared to post-incision NSAIDs For pre-emptive NSAIDs, there is probably a decrease in early acute postoperative pain (MD -0.69, 95% CI -0.97 to -0.41; studies = 36; participants = 2032; I2 = 96%; moderate-certainty evidence). None of the included studies that reported on acute postoperative pain reported adverse events as an outcome. There may be little or no difference between the groups in short-term (RR 1.00, 95% CI 0.34 to 2.94; studies = 2; participants = 100; I2 = 0%; low-certainty evidence) or long-term nausea and vomiting (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 228; I2 = 29%; low-certainty evidence). There may be a reduction in late acute postoperative pain (MD -0.22, 95% CI -0.44 to 0.00; studies = 28; participants = 1645; I2 = 97%; low-certainty evidence). There may be a reduction in 24-hour morphine consumption with pre-emptive NSAIDs (MD -5.62 mg, 95% CI -9.00 mg to -2.24 mg; studies = 16; participants = 854; I2 = 99%; low-certainty evidence) and an increase in the time to analgesic request (MD 17.04 minutes, 95% CI 3.77 minutes to 30.31 minutes; studies = 18; participants = 975; I2 = 95%; low-certainty evidence). There may be little or no difference in opioid adverse events such as pruritus (RR 0.40, 95% CI 0.09 to 1.76; studies = 4; participants = 254; I2 = 0%; low-certainty evidence) or sedation (RR 0.51, 95% CI 0.16 to 1.68; studies = 4; participants = 281; I2 = 0%; low-certainty evidence), although the number of included studies for these outcomes was small. No study reported patient satisfaction, chronic pain or time to first bowel movement for pre-emptive NSAIDs. Preventive NSAIDs compared to post-incision NSAIDs For preventive NSAIDs, there may be little or no difference in early acute postoperative pain (MD -0.14, 95% CI -0.39 to 0.12; studies = 18; participants = 1140; I2 = 75%; low-certainty evidence). One study reported adverse events from NSAIDs (reoperation for bleeding) although the events were low which did not allow any meaningful conclusions to be drawn (RR 1.95; 95% CI 0.18 to 20.68). There may be little or no difference in rates of short-term (RR 1.26, 95% CI 0.49 to 3.30; studies = 1; participants = 76; low-certainty evidence) or long-term (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 456; I2 = 29%; low-certainty evidence) nausea and vomiting. There may be a reduction in late acute postoperative pain (MD -0.33, 95% CI -0.59 to -0.07; studies = 21; participants = 1441; I2 = 81%; low-certainty evidence). There is probably a reduction in 24-hour morphine consumption (MD -1.93 mg, 95% CI -3.55 mg to -0.32 mg; studies = 16; participants = 1323; I2 = 49%; moderate-certainty evidence). It is uncertain if there is any difference in time to analgesic request (MD 8.51 minutes, 95% CI -31.24 minutes to 48.27 minutes; studies = 8; participants = 410; I2 = 98%; very low-certainty evidence). As with pre-emptive NSAIDs, there may be little or no difference in other opioid adverse events such as pruritus (RR 0.56, 95% CI 0.09 to 3.35; studies = 3; participants = 211; I2 = 0%; low-certainty evidence) and sedation (RR 0.84, 95% CI 0.44 to 1.63; studies = 5; participants = 497; I2 = 0%; low-certainty evidence). There is probably little or no difference in patient satisfaction (MD -0.42; 95% CI -1.09 to 0.25; studies = 1; participants = 72; moderate-certainty evidence). No study reported on chronic pain. There is probably little or no difference in time to first bowel movement (MD 0.00; 95% CI -15.99 to 15.99; studies = 1; participants = 76; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There was some evidence that pre-emptive and preventive NSAIDs reduce both pain and morphine consumption, although this was not universal for all pain and morphine consumption outcomes. Any differences found were not clinically significant, although we cannot exclude this in more painful operations. Moreover, without any evidence of reductions in opioid adverse effects, the clinical significance of these results is questionable although few studies reported these outcomes. Only one study reported clinically significant adverse events from NSAIDs administered before surgery and, therefore, we have very few data to assess the safety of either pre-emptive or preventive NSAIDs. Therefore, future research should aim to adhere to the highest methodology and be adequately powered to assess serious adverse events of NSAIDs and reductions in opioid adverse events.

Topical ketamine as a local anesthetic agent in reducing venipuncture pain: A randomized controlled trial.

AIM: Pain control is an important aspect of ED patient management, and there are many different protocols used around the world influenced by both availability of local resources as well as staff competency and experience. This study aims to evaluate the use of topical ketamine in acute pain reduction by directly comparing it to lidocaine-prilocaine (EMLA) cream. MATERIALS AND METHODS: In this randomized clinical trial, 300 adult patients classified as level 4 or 5 by ESI triage system were enrolled. These patients were divided randomly into three groups. The site of venipuncture was covered with 2 g of topical ketamine cream 10% in group one, 2 g of 5% EMLA cream in group two, and finally, in group 3 (control group), was covered with placebo (2 g of cold cream). The primary end point of the study was reported pain severity with secondary end points being onset of local anesthesia as well as any side effects noted. RESULTS: The data gathered showed pain score during venipuncture in both intervention groups were significantly lower when compared to the control group (P < 0.05). However, pain score did not differ between the 2 intervention groups (P = 0.395). There was no statistically significant difference between the ketamine or EMLA in onset of local anesthesia (P = 0.419). We noted itching and irritation was significantly higher in the EMLA group when compared to ketamine(P < 0.05). CONCLUSION: This study showed that local cutaneous ketamine is as effective as EMLA in relieving pain during venipuncture.

Recurrent and acute abdominal pain as the main clinical manifestation in patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease that often leads to misdiagnosis. The delay of diagnosis is > 10 years in China. Recurrent and acute abdominal pain is one of the common symptoms of HAE. Because of the high misdiagnosis rate, it usually results in unnecessary surgical procedures. This study focused on the clinical symptoms and management of HAE-related abdominal attacks in Chinese patients to provide some new insight for the emergency department (ED) physicians and gastroenterologists. Methods: A Web-based survey was conducted among 107 patients with HAE from 94 unrelated families. Detailed questions with respect to the abdominal attacks were asked, including the frequency, symptoms, and duration before and after confirmed diagnosis. The demographic characteristics, diagnosis process, and treatment outcomes were also included. Results: Approximately 70% of the patients with HAE presented with abdominal symptoms during the onset of edema, mostly characterized by pain (94.8%), nausea (83.1%), vomiting (83.1%), diarrhea (59.7%), and constipation (23.4%). The patients were easily misdiagnosed as having gastroenteritis (35.1%) and appendicitis (10.4%), and 24.7% of them received unnecessary appendectomy or laparotomy. Danazol, a widely used drug for long-term prophylaxis of HAE in China, can reduce the attack frequency and alleviate the abdominal symptoms, but the adverse effects are also significant and more severe in women. Conclusions: Abdominal symptoms are common and important clinical features of HAE but are easily confused with other gastrointestinal diseases. ED physicians and gastroenterologists should consider HAE when patients experience recurrent and unexplained abdominal pain. Proper medical treatment should be administered in a timely manner if an HAE diagnosis is confirmed and efforts are required to increase access in China to medications both for on-demand treatment and long-term prophylaxis.

Ultra-purified alginate gel implantation decreases inflammatory cytokine levels, prevents intervertebral disc degeneration, and reduces acute pain after discectomy.

Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.

Selective activation of metabotropic glutamate receptor 7 blocks paclitaxel-induced acute neuropathic pain and suppresses spinal glial reactivity in rats.

RATIONALE: Paclitaxel-induced acute pain syndrome (P-APS), characterized by deep muscle aches and arthralgia, occurs in more than 70% of patients who receive paclitaxel. P-APS can be debilitating for patients and lead to reductions and discontinuation of potentially curable therapy. Despite being relatively common in clinical practice, no clear treatment exists for P-APS and the underlying mechanisms remain poorly defined. Regulation of glutamatergic transmission by metabotropic glutamate receptors (mGluRs) has received growing attention with respect to its role in neuropathic pain. To our knowledge, no study has been conducted on alterations and functions of group III mGluR7 signaling in P-APS. OBJECTIVES: In the present study, we determined whether a single administration of paclitaxel induces glutamatergic alterations and whether mGluR7 activation blocks paclitaxel-induced neuropathic pain by suppressing glial reactivity in the spinal cord. RESULTS: A single paclitaxel injection dose-dependently induced acute mechanical and thermal hypersensitivity, and was associated with increased glutamate level accompanied by reduction in mGluR7 expression in the spinal cord. Selective activation of mGluR7 by its positive allosteric modulator, AMN082, blocked the development of paclitaxel-induced acute mechanical and thermal hypersensitivity, without affecting the normal pain behavior of control rats. Moreover, activation of mGluR7 by AMN082 inhibited glial reactivity and decreased pro-inflammatory cytokine release during P-APS. Abortion of spinal glial reaction to paclitaxel alleviated paclitaxel-induced acute mechanical and thermal hypersensitivity. CONCLUSIONS: There results support the hypothesis that spinal mGluR7 signaling plays an important role in P-APS; Selective activation of mGluR7 by its positive allosteric modulator, AMN082, blocks P-APS in part by reducing spinal glial reactivity and neuroinflammatory process.

Development and evaluation of an educational video for families on the relief of acute pain in babies / Desarrollo y evaluación de un video educativo familiar sobre el alivio del dolor agudo del bebé / Desenvolvimento e avaliação de vídeo educativo para família sobre alívio da dor aguda do bebê

ABSTRACT Objective To develop and evaluate an educational video for active family participation in the relief of acute pain in babies. Methods A methodological and experimental study produced at the University of São Paulo at Ribeirão Preto School of Nursing and at a university hospital in southeastern Brazil, conducted in three operational stages, from January to July 2017. Results The video lasts nine minutes and 31 seconds, and it was validated by 19 expert judges with a 90% agreement among them for content and appearance items. Regarding the evaluation, 16 family members and pregnant women did it and were favorable to its use as an educational technology for learning. Conclusions Both the experts and the target population positively evaluated the video, which can be used as a health education strategy to empower families to engage in the baby pain relief with more autonomy and proactivity.

RESUMEN Objetivo Desarrollar y evaluar un video educativo para la participación activa de la familia en el alivio del dolor agudo en el bebé. Métodos Un estudio metodológico y experimental, producido en la Universidad de San Pablo en la Facultad de Enfermería Ribeirão Preto y en un hospital universitario del sudeste de Brasil, realizado en tres etapas operativas, de enero a julio de 2017. Resultados El video dura nueve minutos y 31 segundos, fue validado por 19 jueces expertos con un 90% de acuerdo entre ellos en cuanto contenido y elementos de aspecto. Con respecto a la evaluación, estuvo a cargo de 16 familiares y mujeres embarazadas, quienes se mostraron favorables a su uso como tecnología educativa para el aprendizaje. Conclusiones Tanto los expertos como el público evaluaron el video de manera positiva, que puede usarse como una estrategia educativa para la salud a fin de empoderar a la familia para que participe en una atención más autónoma y proactiva para el alivio del dolor del bebé.

RESUMO Objetivo Desenvolver e avaliar um vídeo educativo para participação ativa da família no alívio da dor aguda do bebê. Métodos Estudo metodológico, experimental, produzido na Escola de Enfermagem de Ribeirão Preto da Universidade de São Paulo e em um hospital universitário do sudeste do Brasil, conduzido em três etapas operacionais, no período de janeiro a julho de 2017. Resultados O vídeo tem duração de nove minutos e 31 segundos, foi validado por 19 juízes especialistas com concordância de 90% entre eles para os itens de conteúdo e aparência. Quanto a avaliação, 16 familiares e gestantes fizeram-na e foram favoráveis ao uso deste enquanto tecnologia educativa para aprendizagem. Conclusões Tanto os especialistas quanto o público-alvo avaliaram positivamente o vídeo, que pode ser utilizado como estratégia de educação em saúde para empoderar a família a se envolver nos cuidados de alívio da dor aguda do bebê com mais autonomia e proatividade.