Mech-Sense

Pain management in acute pancreatitis (AP) is of critical therapeutic and prognostic significance. We aimed to identify patient phenotypes in AP based on pain management strategies and evaluate their prognostic impact. Data from two major international prospective cohort studies of AP patients (PAINAP study, n = 2119 and APPRENTICE study, n = 1544) from 141 centers worldwide were collated. Demographic data and analgesic use (within 72 h of presentation) were used for latent class analysis of binary analgesic data. The number of clusters was determined by minimisation of Bayesian information criterion. Cluster assignment and AP outcomes were interrogated with multivariable mixed-effects logistic regression. Overall, 3469 patients (median age 52; 47 % female) were analysed. There were 1015 (29.2 %) patients that had moderately severe to severe AP. Within the first 72 h, 494 (14.2 %) patients received non-steroidal anti-inflammatory drugs (NSAIDs), 1410 (40.6 %) weak opioids, 1347 (14.2 %) strong opioids, and 48 (1.4 %) epidural analgesia. There were significant variations in analgesic prescribing patterns across centers (p < 0.001, interclass correlation coefficient 43.8 %). Latent class analysis identified 5 unique patient clusters: early NSAIDs use, minimal analgesic use, strong opioid use, early multimodal analgesia use, and early weak opioid use. The cluster characterized by early NSAIDs was associated with non-severe AP (adjusted odds ratio 0.64, 95 % confidence interval 0.44-0.93, p = 0.02), which could suggest that the use of NSAIDs was perhaps driven by milder pain severity. Unique clusters in the management of pain in AP were identified, with associations to severity of AP. Substantial centre-level variations exist in the patterns of analgesic prescribing globally, contributing to variations in outcomes.

Background and Aims Transcutaneous vagus nerve stimulation has been suggested to alleviate gastrointestinal symptoms in subjects with diabetic autonomic neuropathy. This study aimed to examine the effect of this treatment on magnetic resonance imaging (MRI)-assessed gastrointestinal function. Methods This study included data from a randomized, sham-controlled, double-blind parallel group trial. Subjects with type 1 or 2 diabetes with manifest gastrointestinal symptoms and diabetic autonomic neuropathy were included. Subjects were randomized to one week of active or sham transcutaneous vagus nerve stimulation. A meal-stimulated pan-alimentary MRI scan protocol was performed after the one week stimulation. Gastric, small bowel, and colonic volumes were assessed, as were gastric half-emptying time, small bowel motility, and gastrointestinal symptom scores. Key Results Thirty-four patients were included. Eighteen and sixteen patients were randomized to active and sham treatment, respectively. Gastric, small bowel, and colonic volumes were not different between treatment groups at any post-meal time points after one week of treatment (all p > 0.80). Gastric half-emptying time was not different between active and sham groups (105+/-37 min vs. 101+/-36 min, p = 0.77). Small bowel motility 105 min postprandially was higher in the active group compared to sham (184 ± 53 au. vs. 138+/-28 au., p = 0.04), whereas none of the remaining time points showed any differences (all p > 0.47). Symptom scores were unaffected by treatment (all p > 0.51), and no correlations between symptom scores and MRI measurements were found (all p > 0.16). Conclusions Transcutaneous vagus nerve stimulation did not affect MRI-assessed gastrointestinal function in subjects with diabetic autonomic neuropathy.

Itch can be a side-effect of drugs like opioids, with prevalence depending on the route of administration. This study aimed to investigate if morphine (1) induced itch and neurogenic inflammation after intradermal injection and (2) modulates the responses to locally experimentally induced histaminergic and non-histaminergic itch. Twenty-four healthy volunteers participated in this randomised, single-blinded study. Two areas on the volar forearms of each participant were randomly treated with either intradermal morphine 0.05 mL (0.1 mg/mL) or saline (isotonic saline 0.05 mL), followed by assessment of itch intensity, wheal, and flare reactions. After injection, histamine and cowhage (non-histaminergic itch) were randomly applied intradermally and topically, respectively at the sites of morphine/saline injection, and the assessments were repeated. Before saline/morphine injections (baseline measurement), after injections (post-intervention measurement), and after pruritogen application (post-pruritogen measurement), superficial blood perfusions were measured using full-field laser perfusion imaging. Morphine induced increased peak itch intensity and itch area under the curve compared to saline, without further increase by the experimentally induced histaminergic and non-histaminergic itch. Morphine also caused a larger wheal area compared to saline. Morphine increased superficial blood perfusion compared to saline both after treatment and after pruritogens. This study confirmed that (1) intradermal morphine induces spontaneous itch, (2) morphine induced neurogenic inflammation which alone and in combination with the pruritogens caused larger responses (wheal and flare) when compared with saline and (3) the itch intensities provoked by experimentally induced histaminergic and non-histaminergic substances were not modulated when applied to the morphine-treated areas.

Introduction: In most chronic itch conditions, antihistamines are ineffective, highlighting the necessity to study the mechanisms of non-histaminergic itch to develop new treatments. Polymodal C-fibers, transmitting non-histaminergic itch, can be experimentally activated by BAM8-22, a Mas-related G protein-coupled receptor X1 (MrgprX1) agonist. Moreover, TRPA1 ion channel activation could provoke non-histaminergic itch. This study aimed to explore TRPA1 and MrgprX1 interaction by modulating BAM8-22-induced non-histaminergic itch with the TRPA1 antagonist A-967079. Methods: Four areas on the forearms of 22 healthy subjects were treated as follows: vehicle+BAM8-22, A-967079+BAM8-22, A-967079+BAM8-22 (applied after 5 min), and A-967079+inactivated cowhage spicules. BAM8-22 (2 mg/mL) was applied through inactivated cowhage spicules, while A-967079 (0.5 mg/mL) and vehicle were intradermally injected (0.1 mL). After application, itch was scored for 9 minutes, followed by measurement of superficial blood perfusion and mechanical/thermal sensitivities. Results: Itch evoked by A-967079+BAM8-22 (after 5 min) resulted in a lower (P&lt;0.05) than vehicle+BAM8-22. In A-967079+BAM8-22 (after 5 min) area, mechanically evoked itch was reduced (P&lt;0.05). Conclusions: The TRPA1 antagonist A-967079 reduced BAM8-22-induced non-histaminergic itch, confirming that the TRPA1 receptors may be involved in non-histaminergic itch generation and hence may provide new information helping manage non-histaminergic itch.

An individual participant data (IPD) meta-analysis can assess the predictive value of data on outcomes at the individual level, offering a potential tool for developing personalized pain management. Pretreatment quantitative sensory testing (QST) may stratify patient groups, which are then linked to treatment outcomes. Our objective was to determine if measures of QST at baseline are related to treatment outcomes (at any time point) for pain and disability in lower-limb osteoarthritis. We performed a systematic review with an IPD meta-analysis. Searches were conducted in 9 databases until May 5, 2023 for intervention studies that measured baseline QST and longitudinal measures of participant-reported pain and disability. We performed a 2-stage approach to analyse longitudinal data. Individual models were fitted to each study and combined using random effects multivariate meta-analytic models. Study quality was assessed using the Joanna Briggs Institute checklist, and certainty of the evidence was assessed using GRADE. We identified 3082 records and included 1 hip and 28 knee datasets consisting of 2522 participants from 40 studies. Local warm detection thresholds ( P = 0.024) predicted knee osteoarthritis pain outcomes (very-low certainty). Local warm detection thresholds ( P = 0.030), remote cold detection thresholds ( P = 0.05), and remote pressure tolerance thresholds ( P = 0.007) predicted knee osteoarthritis disability outcomes (very-low certainty). Other QST variables were associated with hip and knee osteoarthritis pain and disability levels (eg, pressure pain thresholds), but this relationship did not change over time. This review finds that mechanism-based, QST methodologies do not consistently predict pain or disability on an individual level in hip or knee osteoarthritis.

BackgroundThe objectives were to determine the prevalence of de novo and persistent pelvic pain after benign hysterectomy and to assess risk factors.MethodsA Swedish prospective multicenter study of 440 women undergoing benign hysterectomy was conducted between October 2011 and March 2017. Measures of pain, the spatial extent of bodily pain, and pain sensitivity were assessed using a self-reporting questionnaire, Margolis’s patient pain drawing, and quantitative sensory testing of pain thresholds for pressure, heat, and cold, respectively. Quality of life was evaluated by EQ-5D-3L and SF-36. Psychological distress was assessed by the Hospital Anxiety and Depression Scaleand the Stress-Coping Inventory. Logistic regression models were used to assess risk factors, and the outcome was presented as an adjusted odds ratio (aOR) and 95% confidence interval (CI).ResultsPreoperatively, 18.0% of the women reported no bodily pain, 41.5% had pelvic pain, either as the only location (7.0%) or along with pain in other locations (34.5%), and 40.5% had non-pelvic pain only. Postoperatively, 6.2% developed de novo pelvic pain and 16.4% had persistent pelvic pain. De novo pelvic pain developed exclusively in women who preoperatively had non-pelvic pain only. Risk factors for de novo pelvic pain were a long hospital stay (aOR 1.50 (95%CI) 1.02–2.21)), high preoperative pain intensity (aOR 1.25 (95%CI 1.01–1.62)) and a high number of pain areas (aOR 1.15 (95%CI 1.05–1.27)), along with anxiety (aOR 10.61 (95%CI 1.84–61.03)) and low EQ-5D-3L health index (aOR 0.02 (95%CI 0.00–0.31)). Risk factors for persistent pelvic pain were lower age (aOR 0.89 (95%CI 0.81–0.97)), higher number of pain areas (aOR 1.08 (95%CI 1.02–1.14)), and a higher frequency of preoperative pain (aOR 12.75 (95%CI 2.24–72.66)).ConclusionAlthough hysterectomy appeared to be reasonably effective in curing pelvic pain, a non-negligible proportion of women developed de novo pelvic pain or had persistent pelvic pain. De novo pelvic pain seemed to affect only those who preoperatively had widespread bodily pain. Women at risk for de novo and persistent pelvic pain after hysterectomy could be identified preoperatively.Trial registrationsThe study was retrospectively registered in ClinicalTrial.gov (NCT01526668) on 01/27//2012.

ABSTRACT Gastrointestinal function plays a pivotal role in nutrient absorption and overall digestive health. Abnormal gastric emptying is closely linked to type 2 diabetes, impacting blood glucose regulation and causing gastrointestinal symptoms. This study aims to investigate and compare segmental transit times, motility indices, and micromilieu between Greenlandic Inuit and Danish individuals with and without type 2 diabetes. We included forty-four Greenlandic Inuit, twenty-three of whom had type 2 diabetes, and age and gender-matched Danish individuals. Segmental transit time, motility, and luminal environment were measured using the SmartPill®. Greenlandic controls displayed shorter gastric emptying time (GET) (163 min), higher gastric median pH (2.0 pH) and duodenal median contractions (18.2 mm Hg) compared to Greenlanders with type 2 diabetes (GET: 235 min, pH:1.9, median duodenal contraction 18.4 mm Hg) and Danish controls (GET: 190, pH:1.2 median duodenal contraction 17.5 mmHg). Despite similar anti-diabetic management efforts, variations in gastrointestinal physiology were evident, highlighting the complexity of diabetes and its interaction with ethnicity, suggesting potential dietary or even genetic influences, emphasising the necessity for personalised diabetes management approaches. Finally, the study opens possibilities for future research, encouraging investigations into the underlying mechanisms linking genetics, diet, and gastric physiology, as an understanding of factors can lead to more effective, tailored strategies for diabetes care and improved digestive health in diverse populations.

To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). A total of 100 participants. Descriptive and comparative analysis from flares questionnaire. The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

Chronic pancreatitis (CP), a condition marked by severe pain, necessitates precise pain assessment for effective treatment. This review explores recent advances in CP pain assessment, including CP-specific tools, quantitative sensory testing (QST), and the emerging use of wearable devices. Unidimensional pain assessment tools are constrained in capturing the multifaceted nature of CP pain. CP-specific tools, such as the Comprehensive Pain Assessment Tool (COMPAT) and its briefer variant, COMPAT-SF, exhibit promise but may necessitate further validation for broader adoption. QST provides a semi-objective method for characterizing pain profiles, and the P-QST consortium is refining QST for CP patients. Additionally, technology is opening new avenues for objective pain assessment. Wearable devices, like smartwatches, can monitor vital signs, activity levels, and sleep quality. While they hold promise for improving pain assessment, their effectiveness requires further validation. Accurate pain assessment is critical for managing CP. Recent developments include tools like COMPAT and COMPAT-SF, QST for characterizing pain profiles, and the potential of wearable devices. These advances can potentially enhance pain assessment and guide personalized treatment strategies. Integration into clinical practice and rigorous validation will be instrumental in improving CP pain assessment and raising the level of patient care.