Blockade of Piezo2 Pathway Attenuates Inflammatory and Neuropathic Pain in the Orofacial Area.

Although previous studies suggest that Piezo2 regulates chronic pain in the orofacial area, few studies have reported the direct evidence of Piezo2's involvement in inflammatory and neuropathic pain in the orofacial region. In this study, we used male Sprague Dawley rats to investigate the role of the Piezo2 pathway in the development of inflammatory and neuropathic pain. The present study used interleukin (IL)-1ß-induced pronociception as an inflammatory pain model. Subcutaneous injection of IL-1ß produced significant mechanical allodynia and thermal hyperalgesia. Subcutaneous injection of a Piezo2 inhibitor significantly blocked mechanical allodynia and thermal hyperalgesia induced by subcutaneously injected IL-1ß. Furthermore, the present study also used a neuropathic pain model caused by the misplacement of a dental implant, leading to notable mechanical allodynia as a consequence of inferior alveolar nerve injury. Western blot analysis revealed increased levels of Piezo2 in the trigeminal ganglion and the trigeminal subnucleus caudalis after inferior alveolar nerve injury. Furthermore, subcutaneous and intracisternal injections of a Piezo2 inhibitor blocked neuropathic mechanical allodynia. These results suggest that the Piezo2 pathway plays a critical role in the development of inflammatory and neuropathic pain in the orofacial area. Therefore, blocking the Piezo2 pathway could be the foundation for developing new therapeutic strategies to treat orofacial pain conditions.

Isolated Trigeminal Mononeuropathy: A Possible COVID-19 Sequelae.

COVID-19 infections have been linked with multiple neurological manifestations. One of the infrequent complications of post-COVID-19 infection is trigeminal neuropathy. Despite its infrequency, few cases of trigeminal neuropathy following COVID-19 infection have been documented in the literature. However, there remains a paucity of evidence regarding isolated trigeminal neuropathy following COVID-19, particularly in cases devoid of pain but characterized by sensory deficits such as loss of sensation and paresthesia only. We describe a clinical case of trigeminal neuropathy that emerged after a COVID-19 infection at our institution. Our case report delves into the clinical presentation of such trigeminal neuropathy that would aid clinicians in including this pathology in their differential diagnosis.

[What determines the overall quality of postoperative pain management? A question of perspective]. / Was ist ausschlaggebend für die Gesamtqualität der postoperativen Schmerztherapie? Eine Frage der Perspektive.

BACKGROUND: The outcome domains pain intensity, pain-related interference, side effects, (treatment) information, participation and personal interaction have all been identified as relevant factors in the management of perioperative pain. However, it is not yet clear which of these are particularly significant for the subjectively perceived overall quality of postoperative pain management. AIM: A newly developed questionnaire was used in this cross-sectional study to assess the relevance of these domains for patients and compare the relevance to healthcare professionals (HCP). METHODS: The patient survey (n = 40) was conducted on the first postoperative day at Jena University Hospital, Germany. In order to investigate group differences, 63 HCP (disciplines: n = 15 anaesthesiology, n = 17 surgery, n = 31 nursing) were recruited. The questionnaire primarily included all pairwise comparisons between the domains with regard to the overall quality of postoperative pain management. The resulting sum scores for each domain were the primary outcome measure, which were analysed using generalized estimating equations. RESULTS: Within the group of patients, there were significant differences in the prioritization of the six outcome domains, with personal interaction followed by intensity and interference having received the highest ratings. There were also significant differences within the domains between the perspectives of patients and HCP, as well as between the HCP themselves. CONCLUSIONS: The study demonstrates that personal interaction and the reduction of pain intensity and interference are three key factors that are significant for patients' experience of postoperative pain management. However, the extent to which the harmonisation of these three factors with those given prominence by HCP would positively impact postoperative pain management remains unclear and should be investigated further.

improving Pain mAnagement for childreN and young people attendeD by Ambulance (PANDA): protocol for a realist review.

Background: Each year in England, 450,000 children and young people (CYP) under 18 years of age are transported by ambulance to emergency departments. Approximately 20% of these suffer acute pain caused by illness or injury. Pain is a highly complex sensory and emotional experience. The intersection between acute pain, unwell CYP and the unpredictable pre-hospital environment is convoluted. Studies have shown that prehospital pain management in CYP is poor, with 61% of those suffering acute pain not achieving effective pain relief (abolition or reduction of pain score by 2 or more out of 10) when attended by ambulance. Consequences of poor acute pain management include altered pain perception, post-traumatic stress disorder and the development of chronic pain. This realist review will aim to understand how ambulance clinicians can provide improved prehospital acute pain management for CYP. Methods: A realist review will be conducted in accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidance. A five-stage approach will be adopted; 1) Developing an Initial Programme Theory (IPT): develop an IPT with key stakeholder input and evidence from informal searching; 2) Searching and screening: conduct a thorough search of relevant research databases and other literature sources and perform screening in duplicate; 3) Relevance and rigour assessment: assess documents for relevance and rigour in duplicate; 4) Extracting and organising data: code relevant data into conceptual "buckets" using qualitative data analysis software; and 5) Synthesis and Programme Theory (PT) refinement: utilise a realist logic of analysis to generate context-mechanism-outcome configurations (CMOCs) within and across conceptual "buckets", test and refine the IPT into a realist PT. Conclusion: The realist PT will enhance our understanding of what works best to improve acute prehospital pain management in CYP, which will then be tested and refined within a realist evaluation. Registration: PROSPERO Registration: CRD42024505978.

National trends in perioperative epidural analgesia use for surgical patients.

STUDY OBJECTIVE: Newer regional anesthesia techniques and minimally invasive surgeries have yielded decreased postoperative pain scores, potentially leading to decreased need for perioperative epidural analgesia. Limited literature is available on trends in usage rates of epidurals. The objective of this study was to identify trends in perioperative epidural analgesia rates among multiple fields of surgery. METHODS: All patients undergoing general, thoracic, urologic, plastic, vascular, orthopedic, or gynecological surgery in 2014-2020 were included from the National Surgical Quality Improvement Program database of over 700 hospitals in the U.S. and 11 different countries. Annual trends in epidural analgesia for all surgeries and each surgical specialty were assessed by mixed effects multivariable logistic regression. The odds ratios (OR) and 99 % confidence intervals (CI) were reported. RESULTS: There were 3,111,435 patients from 2014 to 2020 that were included in the final analysis, in which 107,209 (3.4 %) received perioperative epidural analgesia. Among all surgeries combined, epidural use throughout the study period decreased (OR 0.98 per year, 99 % CI 0.97-0.98, P < 0.001). When only analyzing the surgeries with the top 5 most frequent epidural use per specialty, there was no statistically significant trend in epidural utilization (OR 0.99 per year, 99 % CI 0.99-1.00, P = 0.09). However, there was an increasing trend in epidural utilization in general surgery (OR 1.05 per year, 99 % CI 1.03-1.07, P < 0.001) and vascular surgery (OR 1.08 per year, 99 % CI 1.05-1.10, P < 0.001). CONCLUSION: Rates of perioperative epidural analgesia use has decreased in recent years overall, however, among surgeries within the general surgery and vascular surgery specialty, utilization has increased for procedures that have the highest rates of usage.

Characterizing Acute Low Back Pain in a Community-Based Cohort: Results from a Feasibility Cohort Study.

Introduction: Acute low back pain (LBP) is a common experience; however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, two acute-LBP severity categorization definitions were developed: 1) pain impact frequency (impact-based) and 2) pain intensity (intensity-based) severity categories. The purpose of this manuscript is to describe and then compare these acute-LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological using a feasibility cohort study. Methods: This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios of categorical variables and Hedges' g for continuous variables. Results: Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. Discussion: This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute-LBP. The robust differences observed between these categorization approaches suggest that how we define acute-LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic-LBP.

Chemogenetic inhibition of pain-related neurons in the posterior insula cortex reduces mechanical hyperalgesia and anxiety-like behavior during acute pain.

Pain is a complex phenomenon that involves sensory, emotional, and cognitive components. The posterior insula cortex (pIC) has been shown to integrate multisensory experience with emotional and cognitive states. However, the involvement of the pIC in the regulation of affective behavior in pain remains unclear. Here, we investigate the role of pain-related pIC neurons in the regulation of anxiety-like behavior during acute pain. We combined a chemogenetic approach with targeted recombination in active populations (TRAP) in mice. Global chemogenetic inhibition of pIC neurons attenuates chemically-induced mechanical hypersensitivity without affecting pain-related anxiety-like behavior. In contrast, inhibition of pain-related pIC neurons reduces both mechanical hypersensitivity and pain-related anxiety-like behavior. The present study provides important insights into the role of pIC neurons in the regulation of sensory and affective pain-related behavior.

Dorsal root ganglion stimulation provides significant functional improvement from acute debilitating Crohn's disease: A novel use.

Crohn's disease is a chronic inflammatory bowel condition causing symptoms, notably pain, due to ongoing intestinal inflammation or complications like abscesses, strictures, and fistulas, which are common in IBD patients. Abdominal pain affects up to 60 % of IBD patients, irrespective of disease severity, prompting medical attention. Various medications like NSAIDs, antidepressants, antispasmodics, anticonvulsants, and opioids are used to manage pain, but they have limited effectiveness and potential side effects, even during remission. In this case, a 20-year-old Caucasian female college student [height 5'4″, weight 120lbs (54.4 kg)] with juvenile idiopathic arthritis and Crohn's disease experienced severe daily abdominal pain, negatively impacting her life. Despite a multimodal regimen, including gabapentin, nortriptyline, duloxetine, and acetaminophen, her pain persisted, significantly affecting her appetite, sleep, mood, activity level, and overall quality of life (QOL). To address this, dorsal root ganglion (DRG) stimulation was considered. The patient aimed for a 20 % pain reduction and improved QOL. Trial leads were placed along the T10 and T12 DRG, resulting in a 25 % pain reduction (8-6 out of 10) and substantial QOL improvement. She could eat, sleep without interruptions, walk longer distances, and be more active. The T12 lead was more effective than the T10, targeting upper abdomen stimulation. The patient and her mother were highly satisfied and opted for permanent implantation for the T11 and T12 DRG. While DRG stimulation was approved in 2016 for chronic pain, to our knowledge, this is the first reported case of its use in a patient with debilitating Crohn's disease.

Psychophysical changes after total sleep deprivation and experimental muscle pain.

Sleep disturbances exacerbate chronic pain, increase psychological load, and increase inflammation. Delayed onset muscle soreness (DOMS) mimics aspects of chronic pain, predominantly affecting peripheral pain mechanisms, while experimental sleep provocations have been shown to impact central pain mechanisms. This study aimed to combine a DOMS model with total sleep deprivation (TSD) to create a novel model affecting both peripheral and central pain mechanisms. A total of 30 healthy participants attended two sessions (baseline and follow-up) separated by 24 h of TSD and a home rating after 48 h. Assessments of interleukin 6 (IL-6) levels, sleep quality, pain catastrophising, affect, and symptoms of depression and anxiety were included in the baseline and follow-up sessions. Additionally, pressure pain and tolerance thresholds, temporal summation, and conditioned pain modulation (CPM) were assessed using cuff-pressure algometry in the baseline and follow-up sessions. DOMS was induced with eccentric calf raises during the baseline session followed by 24 h of TSD. At follow-up pain tolerance (p = 0.012) was significantly reduced, and CPM (p = 0.036) was significantly impaired compared to baseline. Psychological changes included decreases in pain catastrophising (p = 0.027), positive affect (p < 0.001), negative affect (p = 0.003), and anxiety (p = 0.012). Explorative regression models predicted 58% and 68% of DOMS pain intensity after 24 and 48 h, respectively, based on baseline body mass index, pain thresholds, psychological measures, and IL-6 (p < 0.01). Combining DOMS with 1 night of TSD induced pain hypersensitivity, impaired CPM, and altered psychological states. A combination of baseline inflammation, psychological measures, and pain sensitivity significantly predicted DOMS pain intensity after 24 and 48 h.

NursPainPrevent: A Prospective Observational Study on Pain During a Bed Bath.

BACKGROUND: Although bed baths are known to cause pain, the engendered pain frequency and intensity remain poorly studied. This prospective, observational study was undertaken to examine prospectively, on a given day, patients' bed bath-associated pain in the general in-hospital population. METHODS: Eight external investigators observed 166 bed baths given in 23 units in 5 hospitals. Using validated assessment scales specific to the patients' clinical situations, they established pain scores. RESULTS: Expert observers rated bed bath-induced pain as moderate-to-severe for 48% of the patients, among whom 51.9% had not received prophylactic analgesia prior to the procedure. Only 7.2% benefited from evaluation with a validated pain scale. Astute attention-distraction techniques were applied to shift attention during 16.8% of the bed baths. Caregivers used verbal guidance for 85% of the procedures, and adapted touch and rhythm of the gestures for 84.3%. CONCLUSION: Bed baths generate moderate-to-severe pain intensity. Evaluation and recourse to analgesia remain insufficient despite caregivers' attention accorded to patient comfort and positioning. CLINICAL IMPLICATIONS: The results of this study could contribute to sensitizing professionals to preventing pain linked with routine nursing care. Four axes for improvement were highlighted: evaluation improvement, analgesia, nonpharmacological approaches, and adapted mobilization techniques.

Drugs used for pain management in gastrointestinal surgery and their implications.

Pain is the predominant symptom troubling patients. Pain management is one of the most important aspects in the management of surgical patients leading to early recovery from surgical procedures or in patients with chronic diseases or malignancy. Various groups of drugs are used for dealing with this; however, they have their own implications in the form of adverse effects and dependence. In this article, we review the concerns of different pain-relieving medicines used postoperatively in gastrointestinal surgery and for malignant and chronic diseases.

Adjunctive use of hypnosis for clinical pain: a systematic review and meta-analysis.

Systematic reviews suggest that stand-alone hypnotic suggestions may improve pain outcomes compared with no treatment, waitlist, or usual care. However, in clinical practice, hypnosis is often provided adjunctively with other interventions, which might have different effects than those reported in previous reviews. This systematic review aimed to summarize the analgesic effects of adjunctive hypnosis in adults with clinical pain. Seven databases (MEDLINE, Embase, PsycINFO, Emcare, SCOPUS, CENTRAL, Cochrane) were searched up to January 2024. Randomised controlled trials comparing the analgesic effects of adjunctive hypnosis (hypnosis + primary intervention) with those of the primary intervention alone were included. Meta-analyses (random-effects model) calculated mean differences (MD, [95% confidence intervals]) for pain intensity (0-100). Seventy studies were pooled in meta-analyses (n = 6078). Hypnosis adjunctive to usual care had a small additional analgesic effect (chronic pain: -8.2 [-11.8, -1.9]; medical procedures/surgical pain: -6.9 [-10.4, -3.3]; burn wound care: -8.8 [-13.8, -3.9]). Hypnosis adjunctive to education had a medium additional analgesic effect for chronic pain (-11.5 [-19.7, 3.3]) but not postsurgery pain (-2.0 [-7.8, 3.7]). When paired with psychological interventions, hypnosis slightly increased analgesia in chronic pain only at the three-month follow-up (-2 [-3.7, -0.3]). Hypnosis adjunctive to medicines had a medium additional analgesic effect for chronic pain (-13.2, [-22.5, -3.8]). The overall evidence certainty is very low; therefore, there is still uncertainty about the analgesic effects of adjunctive hypnosis. However, hypnosis adjunct to education may reduce pain intensity for chronic pain. Clarification of proposed therapeutic targets of adjunctive hypnosis to evaluate underlying mechanisms is warranted.

Risk factors for persistent postoperative opioid use: an entity distinct from chronic postsurgical pain.

Despite a decline in opioid prescriptions over the past decade, patients commonly receive opioid analgesics as a treatment for postoperative pain in the USA. One complication that patients may experience after surgery is persistent postoperative opioid use (PPOU), or opioid use beyond the typical recovery period. Often defined as beyond 3 months postsurgery, PPOU is frequently conflated with chronic postsurgical pain (CPSP), where pain persists well after the expected healing time following surgery. This narrative review explores the distinct risk factors for each condition, their interrelation, and potential future research directions.For PPOU, major risk factors include the risky use of substances including misuse and use disorders; depression and other mental health disorders; a history of chronic pain before surgery including back pain; and certain surgical types (ie, total knee arthropathy, open cholecystectomy, total hip arthropathy). Conversely, CPSP risk factors include the type of surgery (ie, thoracic and breast surgeries), mental health conditions (particularly catastrophizing), and pain in both the preoperative and postoperative phases. Despite the overlap of some factors, studies typically employ different frameworks when examining PPOU and CPSP, with a biopsychosocial model applied for CPSP and little emphasis on an individual's social environment employed for PPOU. Additionally, existing studies predominantly rely on retrospective insurance claims data, which may not capture the full scope of risk factors.To fill gaps in understanding, investigations may prospectively assess and analyze patient-reported outcomes, implement similar frameworks, and concurrently measure both conditions to advance the scientific understanding of PPOU and CPSP.

Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol.

INTRODUCTION: Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. METHODS: We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90 mg/tramadol 50 mg (one packet of granules diluted in 100 ml of water, once a day [QD], for 7 days) or paracetamol 975 mg/tramadol 112.5 mg (one tablet of 325 mg/37.5 mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. RESULTS: One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% - 0.648 (- 0.010 to 1.306)] and 5 days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061-0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland-Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). CONCLUSIONS: The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04968158.

Understanding the role of intraoperative hypothermia in perioperative opioid requirements in immediate implant-based breast reconstruction.

BACKGROUND: The relationship between perioperative temperatures and postoperative pain is unknown. The present study investigated the relationship of intraoperative hypothermia and perioperative opioid requirements after immediate implant-based breast reconstruction. METHODS: A retrospective chart review was conducted on patients undergoing immediate implant-based breast reconstruction from 2019-2023. Patients were classified into the hypothermic group (majority of procedure <36.0 °C) or normothermic group (majority of procedure ≥36.0 °C). Cumulative inpatient opioid requirements (morphine milli-equivalents [MMEs]) and frequency of patients requiring "high-dose opioids" (≥100 MMEs) were collected and compared between the groups. RESULTS: In total, 536 patients (835 breasts) were included, among whom 135 (25.1%) were hypothermic. The hypothermic group had lower mean intraoperative (88.4 vs. 99.1 MMEs, P = 0.007) and postoperative (45.6 vs. 56.8 MMEs, P = 0.006) than the normothermic group. Mean (B = 14.6, P = 0.004) and nadir (B = 10.4, P = 0.038) intraoperative temperatures directly predicted higher opioid requirements while higher percentages of the procedure time spent under 36 °C (B = -27.6, P = 0.004) predicted lower opioid requirements. The hypothermic group was associated with 66% decreased odds of requiring high-dose opioids after adjusting for differences in patient and operative characteristics (P = 0.007). CONCLUSION: Hypothermia is associated with decreased perioperative opioid requirements. Future studies should further investigate ideal temperature thresholds for warming protocols to minimize postoperative pain.

Comparison of the effectiveness of three different distraction methods in reducing pain and anxiety during blood drawing in children: A randomized controlled study.

BACKGROUND: Healthcare professionals need to use effective pain and anxiety-relieving methods during blood drawing in children. AIM: This study aimed to compare the effects of three different distraction methods (Virtual Reality Glasses, Kaleidoscope, and Distraction Cards) in reducing pain and anxiety during blood drawing in children. METHODS: This study was a randomized controlled study. The research was conducted on 400 children between the ages of 7 and 11 years who required blood for routine check-ups upon the doctor's request and who met the sample selection criteria. Children were randomized into four groups: Virtual Reality Glasses, Kaleidoscope, Distraction Cards, and Control Group. Data were collected using the Interview and Observation Form, Wong-Baker FACES Pain Rating Scale, and Children's Fear Scale. Wong-Baker FACES and Children's Fear Scale were assessed and reported by children, parent, and observer. FINDINGS: Pain assessments of the child, parent, and observer after the procedure, and anxiety assessments of the parent, and observer after the procedure in the Virtual Reality Glasses, Kaleidoscope, and Distraction Cards Group were significantly lower than the Control Group (p < 0.001). CONCLUSIONS: All three methods applied to the child during blood drawing were effective in reducing the child's pain and anxiety level. However, it was found that the most effective method to relieve pain and anxiety is virtual reality glasses. PRACTICE IMPLICATIONS: These results contribute to the pain and anxiety management of children during blood drawing. CLINICAL TRIAL REGISTRATION NUMBER: NCT06192498.