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Summary: 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. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is a public health issue, leading to substantial healthcare costs and diminished quality of life for sufferers. While the role of anxiety in pain modulation has been extensively studied, the effects of other emotional states on the body's pain control mechanisms remain less understood. This study sought to explore how different emotions (happiness, anger, sadness, and interest) affect conditioned pain modulation (CPM) and the wind-up phenomenon in healthy adults., Methods: This randomized controlled, cross-over trial involved 28 healthy participants aged 18-60. Participants watched video clips designed to induce specific emotions: happiness, anger, sadness, and interest. Emotional states were assessed using a 7-point Likert scale. Pain modulation was measured using CPM and the wind-up phenomenon. CPM was assessed with a hot water bath as the conditioning stimulus and pressure pain tolerance as the test stimulus. Wind-up was measured using pinprick needle stimulators and a visual analog scale. Data were analyzed using paired t tests to compare pre- and post-emotion induction values., Results: Significant changes in emotional self-assessment values were observed for all emotions. Happiness increased CPM (4.6 ± 11.4, p = 0.04277), while sadness - 9.9 ± 23.1, p = 0.03211) and anger - 9.1 ± 23.3, p = 0.04804) decreased it. Interest did not significantly alter CPM (- 5.1 ± 25.8, p = 0.31042). No significant effects were found for the wind-up phenomenon across any emotional states., Conclusion: This study shows that emotional states significantly affect the body's ability to modulate pain. Positive emotions like happiness enhance pain inhibition, while negative emotions such as sadness and anger impair it. These findings suggest that emotional modulation techniques could be integrated into pain management strategies to improve patient outcomes. Further research should explore a broader range of emotions and include objective measures to validate these results., (© 2024. The Author(s).)

Background: Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom., Objectives: This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens., Methods: In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment., Results: Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27)., Conclusions: LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lang-Illievich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data., Methods: In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients' experience of treatment success and quality of life., Results: The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment., Conclusion: Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged., (© 2024. The Author(s).)

Introduction: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances., Objective: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship., Methods: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed., Results: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization., Conclusion: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena., (© 2024. The Author(s).)

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.

Smoking is a known risk factor for developing various pain-related disorders. However, acute pain often triggers the craving for cigarette consumption, resulting in a positive feedback mechanism. In addition, there is evidence of decreased pain tolerance during the early stages of abstinence. Therefore, in this study, we aimed to investigate whether a period of decreased pain tolerance and increased pain intensity occurs during smoking cessation. A systematic literature search was conducted through PubMed and Web of Science databases for controlled studies investigating the influence of smoking cessation on acute (defined as pain presentation of < 3 months) and postoperative pain. The outcomes of interest included pain perception threshold, pain tolerance, pain intensity, and postoperative opioid requirements. The search strategy yielded 1478 studies, of which 13 clinical studies met our inclusion criteria. The included studies collectively represented data from 1721 participants from four countries. Of these, 43.3% of the included individuals were females. The mean age of the included subjects was 44.2 ± 8.2 years. The duration of smoking cessation varied considerably. The shortest duration was 2 h; others investigated the effect after more than 1 month of smoking cessation. Smokers had a history of 14.6 ± 9.9 years of nicotine abuse. The mean number of daily smoked cigarettes was 17.5 ± 10.3. Most studies examined in this systematic review show a negative influence of smoking cessation on acute pain. However, the affected pain modalities, the duration of the altered pain perception, and whether male and female smokers are equally affected could not be ascertained due to high heterogeneity and few available studies., (© 2022. The Author(s).)

Palmitoylethanolamide (PEA) is marketed as a "dietary food for special medical purposes". Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, "Repetitive phasic heat application", which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation.

Background: Web-based analysis of search queries has become a very useful method in various academic fields for understanding timely and regional differences in the public interest in certain terms and concepts. Particularly in health and medical research, Google Trends has been increasingly used over the last decade., Objective: This study aimed to assess the search activity of pain-related parameters on Google Trends from among the most populated regions worldwide over a 3-year period from before the report of the first confirmed COVID-19 cases in these regions (January 2018) until December 2020., Methods: Search terms from the following regions were used for the analysis: India, China, Europe, the United States, Brazil, Pakistan, and Indonesia. In total, 24 expressions of pain location were assessed. Search terms were extracted using the local language of the respective country. Python scripts were used for data mining. All statistical calculations were performed through exploratory data analysis and nonparametric Mann-Whitney U tests., Results: Although the overall search activity for pain-related terms increased, apart from pain entities such as headache, chest pain, and sore throat, we observed discordant search activity. Among the most populous regions, pain-related search parameters for shoulder, abdominal, and chest pain, headache, and toothache differed significantly before and after the first officially confirmed COVID-19 cases (for all, P<.001). In addition, we observed a heterogenous, marked increase or reduction in pain-related search parameters among the most populated regions., Conclusions: As internet searches are a surrogate for public interest, we assume that our data are indicative of an increased incidence of pain after the onset of the COVID-19 pandemic. However, as these increased incidences vary across geographical and anatomical locations, our findings could potentially facilitate the development of specific strategies to support the most affected groups., (©Istvan-Szilard Szilagyi, Torsten Ullrich, Kordula Lang-Illievich, Christoph Klivinyi, Gregor Alexander Schittek, Holger Simonis, Helmar Bornemann-Cimenti. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.04.2021.)

Background: Several studies have shown that cholinergic mechanisms play a pivotal role in the anti-nociceptive system by acting synergistically with morphine and reducing postoperative opioid consumption. In addition, the anti-cholinesterase drug physostigmine that increases synaptic acetylcholine concentrations has anti-inflammatory effects., Methods: In this randomised placebo-controlled trial including 110 patients undergoing nephrectomy, we evaluated the effects of intraoperative physostigmine 0.5 mg h -1 i.v. for 24 h on opioid consumption, hyperalgesia, pain scores, and satisfaction with pain control., Results: Physostigmine infusion did not affect opioid consumption compared with placebo. However, the mechanical pain threshold was significantly higher (2.3 [sd 0.3]) vs 2.2 [0.4]; P=0.0491), and the distance from the suture line of hyperalgesia (5.9 [3.3] vs 8.5 [4.6]; P=0.006), wind-up ratios (2.2 [1.5] vs 3.1 [1.5]; P=0.0389), and minimum and maximum postoperative pain scores at 24 h (minimum 1.8 [1.0] vs 2.4 [1.2]; P=0.0451; and maximum 3.2 [1.4] vs 4.2 [1.4]; P=0.0081) and 48 h (minimum 0.9 [1.0] vs 1.6 [1.1]; P=0.0101; and maximum 2.0 [1.5] vs 3.2 [1.6]; P=0.0029) were lower in the study group. Pain Disability Index was lower and satisfaction with pain control was higher after 3 months in the physostigmine group., Conclusions: In contrast to previous trials, physostigmine did not reduce opioid consumption. As pain thresholds were higher and hyperalgesia and wind-up lower in the physostigmine group, we conclude that physostigmine has anti-hyperalgesic effects and attenuates sensitisation processes. Intraoperative physostigmine may be a useful and safe addition to conventional postoperative pain control., Clinical Trial Registration: EudraCT number 2012-000130-19., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model., Methods: This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control., Results: Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity., Conclusions: Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects-especially in the absence of reported side effects-make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials.

Pain therapy often entails gastrointestinal adverse events. While opioids are effective drugs for pain relief, the incidence of opioid-induced constipation (OIC) varies greatly from 15% to as high as 81%. This can lead to a significant impairment in quality of life, often resulting in discontinuation of opioid therapy. In this regard, a good doctor-patient relationship is especially pivotal when initiating opioid therapy. In addition to a detailed history of bowel habits, patient education regarding the possible gastrointestinal side effects of the drugs is crucial. In addition, the bowel function must be regularly evaluated for the entire duration of treatment with opioids. Furthermore, if the patient has preexisting constipation that is well under control, continuation of that treatment is important. In the absence of such history, general recommendations should include sufficient fluid intake, physical activity, and regular intake of dietary fiber. In patients of OIC with ongoing opioid therapy, the necessity of opioid use should be critically reevaluated in terms of an with acceptable quality of life, particularly in cases of non-cancer pain. If opioids must be continued, lowering the dose may help, as well as changing the type of opioid. If these measures do not suffice, the next step for persistent OIC is the administration of laxatives. If these are ineffective as well, treatment with peripherally active μ-opioid receptor antagonists should be considered. Enemas and irrigation are emergency measures, often used as a last resort.