Opioid-free anesthesia (OFA) is a heterogeneous group of general anesthesia techniques in which the intraoperative use of opioids is eliminated. This strategy aims to decrease the risk of complications and improve the patient\'s safety and comfort. Such potential advantages are particularly beneficial for selected groups of patients, among them obese patients undergoing laparoscopic bariatric surgery. Opioids have been traditionally used as an element of balanced anesthesia, and replacing them requires using a combination of coanalgesics and various types of local and regional anesthesia, which also have their side effects, limitations, and potential disadvantages. Moreover, despite the growing amount of evidence, the empirical data on the superiority of OFA compared to standard anesthesia with multimodal analgesia are contradictory, and potential benefits in many studies are being questioned. Additionally, little is known about the long-term sequelae of such a strategy. Considering the above-mentioned issues, this study aims to present the potential benefits, risks, and difficulties of implementing OFA in bariatric surgery, considering the current state of knowledge and literature.

Background: In vascular medicine, peripheral arterial disease (PAD) and diabetic foot syndrome (DFS) are often considered synonymous with respect to the need for revascularization. In PAD patients, clinical symptoms reflect the degree of atherosclerotic disease, since peripheral innervation, including pain sensation, is not usually compromised. In DFS patients, however, symptoms of relevant foot ischemia are often absent and progression of ischemia goes unnoticed owing to diabetic polyneuropathy, the loss of nociception being the main trigger for foot ulcers. This review analyzes the fundamental differences between PAD and DFS against the background of polyneuropathy. Methods: The literature research for the 2014 revision of the German evidence-based S3-PAD-guidelines was extended to 2023. Results: Vascular examination is imperative for both, PAD and DFS. Stage-dependent revascularization is of utmost importance in PAD patients, especially those suffering from critical limb-threatening ischemia (CLTI). Successful therapy of DFS goes further, including infection and metabolic control, wound management, offloading the foot and lifelong prophylaxis in the course of a multidisciplinary treatment concept. Revascularization is not needed in all cases of DFS. Conclusions: There are fundamental differences between PAD and DFS with respect to pathophysiology, the anatomical distribution of arterial occlusive processes, the clinical symptoms, the value of diagnostic tools such as the ankle-brachial index, and classification. Also, therapeutic concepts differ substantially between the two patient populations.

Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the PRISMA-ScR guidelines and a more focused analysis of cortisol change after cold pain induction using the direction of effect analysis combined with risk of bias analysis using ROBINS-I. Five data bases were searched systematically for articles on adults with acute pain secondary to disease, injury, or experimentally induced pain. Forty three articles met the inclusion criteria for the general review and 11 of these were included in the cortisol-cold pain analysis. Salivary melatonin, kallikreins, pro-inflammatory cytokines, soluable TNF-α receptor II, secretory IgA, testosterone, salivary α-amylase (sAA) and, most commonly, cortisol have been studied in relation to acute pain. There is greatest information about cortisol and sAA which both rise after cold pain when compared with other modalities. Where participants have been subjected to both pain and stress, stress is consistently a more reliable predictor of salivary biomarker change than pain. There remain considerable challenges in identifying biomarkers that can be used in clinical practice to guide the measurement of nociception and treatment of pain. Standardization of methodology and researchers\' greater awareness of the factors that affect salivary biomolecule concentrations are needed to improve our understanding of this field towards creating a clinically relevant body of evidence.

BACKGROUND: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways.
METHODS: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review.
RESULTS: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development.
CONCLUSIONS: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

BACKGROUND: The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE) monitor has been designed to be an objective, non-invasive tool for the assessment of pain and discomfort in children under 2 years of age. The aim of this systematic review was to evaluate the ability of NIPE to assess pain in neonates and infants during surgical and/or painful procedures.
METHODS: A systematic review (2010-2023) was conducted using PRISMA guidelines. Studies containing children above 2-years-old were excluded. The ROBINS-I (Risk of Bias in Non-randomised Studies of Interventions) tool was used to assess the quality of included studies.
RESULTS: 9 databases were searched identifying 470 articles, 460 did not meet the inclusion criteria and were excluded; therefore, 10 studies with 548 participants were included. NIPE was used to assess intraoperative and postoperative pain for surgery under general anaesthesia (5 studies), as well as acute and prolonged pain from other interventional procedures (5 studies). For surgery under general anaesthesia: NIPE has shown to detect nociceptive events (e.g., skin incision, intubation), insufficient analgesia intraoperatively and to predict early postoperative pain. For painful interventional procedures: NIPE has shown to detect acute pain with a high sensitivity and negative predictive value.
CONCLUSIONS: NIPE has been used to assess pain in surgery and for various painful procedures. NIPE can detect intraoperative pain and reflect early postoperative pain. NIPE may be useful in evaluating procedural pain, however with heterogenous outcomes, more studies are required to confirm its efficacy.
METHODS: Systematic Review.
METHODS: Level II.

Chronic pain has increasingly become a significant health challenge, not just as a symptomatic manifestation but also as a pathological condition with profound socioeconomic implications. Despite the expansion of medical interventions, the prevalence of chronic pain remains remarkably persistent, prompting a turn towards non-pharmacological treatments, such as therapeutic education, exercise, and cognitive-behavioral therapy. With the advent of cognitive neuroscience, pain is often presented as a primary output derived from the brain, aligning with Engel\'s Biopsychosocial Model that views disease not solely from a biological perspective but also considering psychological and social factors. This paradigm shift brings forward potential misconceptions and over-simplifications. The current review delves into the intricacies of nociception and pain perception. It questions long-standing beliefs like the cerebral-centric view of pain, the forgotten role of the peripheral nervous system in pain chronification, misconceptions around central sensitization syndromes, the controversy about the existence of a dedicated pain neuromatrix, the consciousness of the pain experience, and the possible oversight of factors beyond the nervous system. In re-evaluating these aspects, the review emphasizes the critical need for understanding the complexity of pain, urging the scientific and clinical community to move beyond reductionist perspectives and consider the multifaceted nature of this phenomenon.

The analgesia nociception index (ANI) has emerged as a potential measurement for objective pain assessment during general anesthesia. This systematic review and meta-analysis aimed to evaluate the accuracy and effectiveness of ANI in assessing intra- and post-operative pain in patients undergoing general anesthesia. We conducted a comprehensive search of Ovid-MEDLINE, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, public clinical trial databases (ClinicalTrials and Clinical Research Information Service), and OpenSIGLE to identify relevant studies published prior to May 2023 and included studies that evaluated the accuracy and effectiveness of ANI for intra- or post-operative pain assessment during general anesthesia. Among the 962 studies identified, 30 met the eligibility criteria and were included in the systematic review, and 17 were included in the meta-analysis. For predicting intra-operative pain, pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under curve of ANI were 0.81 (95% confidence interval [CI] = 0.79-0.83; I2 = 68.2%), 0.93 (95% CI = 0.92-0.93; I2 = 99.8%), 2.32 (95% CI = 1.33-3.30; I2 = 61.7%), and 0.77 (95% CI = 0.76-0.78; I2 = 87.4%), respectively. ANI values and changes in intra-operative hemodynamic variables showed statistically significant correlations. For predicting post-operative pain, pooled sensitivity, specificity, and DOR of ANI were 0.90 (95% CI = 0.87-0.93; I2 = 58.7%), 0.51 (95% CI = 0.49-0.52; I2 = 99.9%), and 3.38 (95% CI = 2.87-3.88; I2 = 81.2%), respectively. ANI monitoring in patients undergoing surgery under general anesthesia is a valuable measurement for predicting intra- and post-operative pain. It reduces the use of intra-operative opioids and aids in pain management throughout the perioperative period.

Acute postoperative pain remains a critical treatment priority and has prompted a search for technologies and techniques to assist with intra-operative analgesic monitoring and management. Anaesthetists traditionally rely on clinical judgement to guide intra-operative analgesia, but several emerging technologies such as the nociception level index herald the possibility of routine intra-operative analgesia monitoring. However, the impact of devices like nociception level index on postoperative outcomes has not been proven. We undertook a systematic review and meta-analysis of articles which compared nociception level index-guided analgesia to standard care. The primary outcomes were pain intensity and opioid consumption during the first 60-120 min after surgery. Secondary outcomes were the incidence of postoperative nausea and vomiting and duration of stay in the post-anaesthesia care unit. Ten studies, collectively including 662 patients and published between 2019 and 2023, met inclusion criteria for both the qualitative systematic review and quantitative meta-analysis. Risk of methodological bias was generally low or unclear, and six studies reported a significant conflict of interest relevant to their findings. Our meta-analysis was performed using a random-effects model. It found statistically significant benefits of nociception level index-guided analgesia for early postoperative pain (mean (95%CI) difference -0.46 (-0.88 to -0.03) on an 11-point scale, p = 0.03), and opioid requirement (mean (95%CI) difference -1.04 (-1.94 to -0.15) mg intravenous morphine equivalent, p = 0.02). Our meta-analysis of the current literature finds that nociception level index-guided analgesia statistically significantly reduces reported postoperative pain intensity and opioid consumption but fails to show clinically relevant outcomes. We found no evidence that nociception level index-guided analgesia affected postoperative nausea and vomiting nor duration of stay in the post-anaesthesia care unit.

Pain refers to the subjective, unpleasant experience that is related to illness or injury. In contrast to pain, nociception refers to the physiological neural processing of noxious stimuli, such as intra-operative surgical stimuli. One novel device, the Analgesia Nociception Index (ANI), aims to objectively measure intra-operative nociception by analyzing the heart rate variability in patients undergoing surgery. Through this method of nociceptive monitoring, the ANI device aims to provide an objective, continuous evaluation of patient comfort levels and allow anesthesiologists to better manage surgical stress and patient analgesia, perhaps with even better efficacy than current practices used to assess nociception. Additionally, ANI may have clinical application in settings outside of the operating room, such as in the intensive care unit. In this narrative review, we compiled and summarized the findings of many studies that have investigated ANI\'s validity and applications in different clinical settings. Currently, the literature appears mostly supportive of ANI\'s ability to detect nociception in both surgical and non-surgical settings. However, the ability for ANI to provide clinical benefits, such as decreased intra-operative opioid use, post-operative opioid use, and post-operative pain compared to standard practices appear controversial. Because of the wide variety of methodology, clinical settings, patient populations, and limitations in these studies, more investigation of ANI is needed before any firm conclusions can be drawn on its clinical benefits.

The use of medicinal plants to treat inflammatory conditions and painful processes has attracted the attention of scientists and health professionals due to the evidence that natural products can promote significant therapeutic benefits associated with fewer adverse effects compared to conventional anti-inflammatory drugs. The genus Plectranthus is composed of various plants with pharmacological potential, which are used to treat various diseases in traditional communities worldwide. The present study systematically reviewed Plectranthus species with anti-inflammatory and analgesic potential. To this end, a systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search was conducted on the following databases: PubMed, ScienceDirect, SciVerse Scopus, and Web of Science. Different combinations of search terms were used to ensure more excellent article coverage. After the selection, a total of 45 articles were included in this review. This study identified twelve Plectranthus species indicated for the treatment of different inflammatory conditions, such as wounds, fever, bronchitis, abscess, asthma, hepatitis, labyrinthitis, tonsillitis, and uterine inflammation. The indications for pain conditions included headache, sore throat, heartburn, menstrual cramp, colic, toothache, stomachache, migraine, chest pain, abdominal pain, local pain, labor pain, and recurring pain. Among the listed species, ten plants were found to be used according to traditional knowledge, although only four of them have been experimentally studied. When assessing the methodological quality of preclinical in vivo assays, most items presented a risk of bias. The SR results revealed the existence of different Plectranthus species used to treat inflammation and pain. The results of this systematic review indicate that Plectranthus species have the potential to be used in the treatment of diseases with an inflammatory component, as well as in the management of pain. However, given the risk of biases, the experimental analysis of these species through preclinical testing is crucial for their safe and effective use.