Acute pain: Journals & articles

Keywords: Acute pain; Multimodal pain control; Naltrexone; Opioids; Post-surgical pain.

Keywords: Analgesia; Emergency department; Pre-hospital; Sufentanil; Systematic review.

Keywords: Adverse Drug Event; Analgesics; Burns; Opioid; Pain.

Keywords: Acute pain; Patient satisfaction; Patient-centred care; Shared decision-making.

Keywords: Erector spinae plane block; Postoperative pain; Thoracoscopic lobectomy.

Keywords: Acute Pain; Anesthesia, Local; Pain Management.

Keywords: High-sensitivity cardiac troponin; chest pain; emergency department; outcomes; cardic troponin.

Background: This prospective, open-label trial was conducted to fulfil a post-approval commitment made to the competent authorities to extend the indication of the strong opioid analgesic tapentadol hydrochloride oral solution (OS) to the pediatric population.

Patients and methods: The trial assessed the pharmacokinetic (PK) profile of tapentadol, tapentadol-O-glucuronide and tapentadol-O-sulfate after administration of multiple doses of tapentadol OS (1.25 mg tapentadol/kg bodyweight every 4 h for up to 72 h) in children aged 2 to <7 years after a painful event that produces acute pain requiring treatment with a strong analgesic. The obtained PK data were integrated into a previously developed population PK (popPK) model based on single-dose data and then a model-based PK evaluation was performed. The primary trial endpoint was the area under the concentration-time curve at steady state for the dosing interval (AUCτ,ss) for tapentadol.

Results: Ten children received tapentadol OS; all completed the trial. Multiple administrations of the trial medication resulted in tapentadol serum concentrations within the concentration range predicted by the previously developed popPK model. The estimated model-based AUCτ,ss values for tapentadol ranged from 142 to 321 h•ng/mL. They were within the predicted exposure range with no higher than expected accumulation for the employed dosing regimen and also within the targeted steady state exposure range observed in adults receiving multiple doses of immediate release tapentadol 50 to 100 mg. The treatment regimen was safe and well tolerated.

Conclusion: The findings confirm the linear and predictable PK profile of tapentadol hydrochloride. The good agreement between the observed data and the model predictions shows the value of modelling and simulations in the planning and analysis of pediatric clinical trials and the ability to utilize the established PK models to predict multiple dose exposure.

Objectives: To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials.

Methods: A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo.

Results: Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: -2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea.

Conclusions: The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

Abstract
RATIONALE AND SCOPE OF THE GUIDELINES Pain is a subjective unpleasant sensory and emotional experience. Acute pain occurs irrespective of age and has a prevalence of about 5% of the general population. Surgical procedures and painful diagnostic procedures are the main causes of this unpleasant and dangerous phenomenon for hospitalized children. It should be remembered that maintaining homeostasis in a child undergoing surgery is also affected by provision of an adequate level of analgesia and sedation as well as nerve conduction block within the surgical site. Even though both paediatric anaesthesiologists and paediatric surgeons know that the therapeutic activities during the perioperative period should be focused on ensuring sufficient analgesia and haemodynamic stability in surgical patients, as many as 70% of children undergoing surgery may experience moderate to severe pain [1-7]. Moreover, pain management is one of the fundamental human rights, i.e. the right to relief of suffering. According to the declaration of the 13th World Congress on Pain in Montreal (September 2010), this right also includes children [8, 9]. In Poland, the law was amended in 2017, and now each patient is guaranteed the right to relief and treatment of pain (Journal of Laws of 2017, item 836). Unfortunately, this right is not always respected in paediatric patients. Many factors contribute to ineffective analgesia in paediatric patients, mainly insufficient knowledge and lack of experience (concerning the use of opioids in particular), as well as lack of management standards, the negative attitude of the personnel or poor organization [10-13]. In hospitals which, as a result of organizational changes, have implemented analgesic treatment regimens and regularly educate their personnel in these issues, both efficiency and effectiveness of pain relief in children are high [14]. For many years, Polish paediatric anaesthesio-logists have been promoting and streamlining the analgesic management of children, which has led to the development of the present publication. The regimens presented in it are based on both the latest medical reports and many years of the authors' experience. The classes of recommendations and levels of evidence have been prepared (Tables 1 and 2, respectively). The presented recommendations were formulated based on a survey of medical reports published in the last two decades.

Preclinical studies have demonstrated the analgesic potential of cannabidiol (CBD). Those suggesting an effect on pain-processing receptors have brought CBD back into focus. This study assessed the effect of CBD on acute pain, hyperalgesia, and allodynia compared with placebo. Twenty healthy volunteers were included in this randomized, placebo-controlled, double-blinded, crossover study assessing pain intensities (using numeric rating scale), secondary hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a well-established acute pain model with intradermal electrical stimulation. The authors compared the effect of 800-mg orally administered CBD on pain compared with placebo. They further examined the effect on hyperalgesia and allodynia. Cannabidiol whole blood levels were also measured. Pain ratings (mean ± SD) did not differ significantly after CBD application compared with placebo (5.2 ± 0.7 vs 5.3 ± 0.7, P-value 0.928), neither did the areas of hyperalgesia and allodynia differ significantly after CBD application compared with placebo (hyperalgesia 23.9 ± 19.2 cm2 vs 27.4 ± 17.0 cm2, P-value 0.597; allodynia 16.6 ± 13.1 cm2 vs 17.3 ± 14.1 cm2, P-value 0.884). The CBD whole blood level (median, first to third quartile) was 2.0 µg/L (1.5-5.1) 60 minutes and 5.0 µg/L (4.0-10.4) 130 minutes after CBD application. Although the oral application of 800-mg CBD failed to show a significant effect, it is important to focus future research on different dosing, routes of administration, and CBD as a part of multimodal treatment strategies before negating its effects on acute pain.

Opioids in general and remifentanil in particular can induce hyperalgesia. Preclinical data suggest that cannabidiol might have the capacity to reduce opioid-induced hyperalgesia (OIH). Thus, we investigated the effect of oral cannabidiol on OIH in healthy volunteers using an established pain model. Twenty-four healthy participants were included in this randomized, double-blinded, crossover study and received either a 1600-mg single-dose oral cannabidiol or placebo. Hyperalgesia, allodynia, and pain were induced by intracutaneous electrical stimulation. To provoke OIH, participants recieved an infusion of 0.1 µg/kg/min remifentanil over a time frame of 30 minutes, starting 100 minutes after oral cannabidiol ingestion. The primary outcome was the area of hyperalgesia (in square centimetres) up to 60 minutes after remifentanil administration. The area of allodynia (in square centimetres) and pain (numeric rating scale) were also assessed.Cannabidiol had no significant effect on hyperalgesia, allodynia, or pain at any time point of measurement compared with placebo. The area of hyperalgesia after remifentanil administration significantly increased compared with baseline (17.0 cm2 [8.1-28.7] vs 25.3 cm2 [15.1-39.6]; P = 0.013). Mean cannabidiol blood levels were 4.1 ± 3.0 µg/L (mean ± SD) at 130 minutes after ingestion and were 8.2 μg/L ± 6.9 µg/L (mean ± SD) at 200 minutes. Cannabidiol was well tolerated. We conclude that a high single-oral dose of 1600-mg cannabidiol is not effective in reducing OIH. Before excluding an effect of cannabidiol on OIH, research should focus on drug formulations enabling higher cannabidiol concentrations.

Recent sham-controlled studies suggest placebo effects contribute to acute pain relief following mindfulness interventions. However, the specific effects of mindfulness processes and their interaction with placebo effects remain unclear. This study aimed to characterize the role of mindfulness and placebo processes underlying mindfulness-based pain attenuation. Both treatment (focused-attention mindfulness vs sham) and instruction ("told mindfulness" vs "told sham") were manipulated in a balanced placebo design. Changes in acute heat pain were evaluated in 153 healthy adults randomized to receive 6 x 20 minutes of one of the four treatment by instruction interventions or no treatment. Participants receiving any intervention demonstrated improved pain outcomes (unpleasantness, intensity and tolerance) relative to no treatment. The instruction manipulation increased expectation for pain relief in those told mindfulness relative to told sham, but there were no main effects or interactions of treatment or instruction on pain outcomes. However, irrespective of actual intervention received, the belief of receiving mindfulness predicted increased pain threshold and tolerance, with expectancy fully mediating the effect on pain tolerance. These findings suggest a lack of specific effects of mindfulness and instruction on acute pain. Nonetheless, participants' expectancies and beliefs about the treatment they received did predict pain relief. Together with the overall improvement following any intervention, these findings suggest that expectancy and belief may play a stronger role in attenuating acute pain in novices following brief mindfulness interventions than the actual mindfulness-specific processes or instructions delivered.

Purpose: Ketamine is a N-methyl-D-aspartate (NMDA) antagonist with strong analgesic properties. Its addition to the treatment of neuropathic pain may reduce pain intensity and improve overall quality of life. A systematic review and meta-analysis of randomized controlled trials was performed to investigate the addition of ketamine to the treatment of patients with neuropathic pain.

Patients and methods: GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to rate the overall certainty of the evidence for each outcome. Eighteen (18) randomized controlled trials including 706 participants were included for further analysis.

Results: Ketamine addition to standard treatment of neuropathic pain (NP) resulted in a statistically significant reduction of pain intensity at one week after the end of treatment with ketamine (MD -2.14, 95% CI -2.65 to -1.63; p<0.00001) and after 30 days after the end of treatment with ketamine (MD -1.68, 95% CI -2.25 to -1.12; p<0.00001) and a statistically significant increase in discomfort (RR 4.06; 95% CI 1.18 to 13.95; p=0.03), and psychedelic effects (RR 4.94; 95% CI 2.76 to 8.84; p<0.00001).

Conclusion: There is a statistically significant pain reduction by adding ketamine to the treatment of chronic NP when compared to the standard treatment. However, such pain reduction comes at the expense of adverse outcomes, especially psychedelic effects related to the administration of ketamine. However, the overall quality of certainty of evidence is low due to the clinical heterogeneity among the intervention characteristics of the trials analyzed (different administration routes, dosing regimen, therapy durations, different clinical characteristics of the population investigated). Future large multi-centered trials are necessary to confirm or not the results of the present review.

This open access journal is the official Journal of the Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM), covering clinical and basic research, education, patient care, health economics, and policy to inform all practitioners in pain management, such as anesthesiologists, interventional pain physicians, neurosurgeons, neurologists, and any specialists who are interested in pain medicine.

The Clinical Journal of Pain explores all aspects of pain and its effective treatment, bringing you the insights of leading anesthesiologists, surgeons, internists, neurologists, orthopedists, psychiatrists and psychologists, clinical pharmacologists, and physical and rehabilitation therapists.

PAIN® is the official publication of the International Association for the Study of Pain® (IASP®). PAIN® publishes original research on the nature, mechanisms, and treatment of pain and provides a multidisciplinary forum for the dissemination of research in the basic and clinical sciences.

Pain Medicine is dedicated to pain clinicians, educators, and researchers with an interest in pain from various medical specialties and related health disciplines. The journal reflects the rapid growth in pain science and practice, as well as the field's need for policy, ethical, and forensic commentary on pain and its management. It promotes the visibility and development of pain medicine as a worldwide interdisciplinary medical specialty within a collaborative, multidisciplinary pain field.

Pain Practice, the official journal of the World Institute of Pain, publishes international multidisciplinary articles on pain and analgesia that provide its readership with up-to-date research, evaluation methods, and techniques for pain management.