Chronic Constriction Injury of the Distal Infraorbital Nerve (DIoN-CCI) in Mice to Study Trigeminal Neuropathic Pain.

Animal models remain necessary tools to study neuropathic pain. This manuscript describes the distal infraorbital nerve chronic constriction injury (DIoN-CCI) model to study trigeminal neuropathic pain in mice. This includes the surgical procedures to perform the chronic constriction injury and the postoperative behavioral tests to evaluate the changes in spontaneous and evoked behavior that are signs of ongoing pain and mechanical allodynia. The methods and behavioral readouts are similar to the infraorbital nerve chronic constriction injury (IoN-CCI) model in rats. However, important changes are necessary for the adaptation of the IoN-CCI model to mice. First, the intra-orbital approach is replaced by a more rostral approach with an incision between the eye and the whisker pad. The IoN is thus ligated distally outside the orbital cavity. Secondly, due to the higher locomotor activity in mice, allowing rats to move freely in small cages is replaced by placing mice in custom-designed and constructed restraining devices. After DIoN ligation, mice exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are similar to those in IoN-CCI rats, i.e., increased directed face grooming and hyperresponsiveness to von Frey hair stimulation of the IoN territory.

Evaluating the Predictive Value of a Short Preoperative Holistic Risk Factor Screening Questionnaire in Preventing Persistent Pain in Elective Adult Surgery: Study Protocol for a Prospective Observational Pragmatic Trial [PERISCOPE].

Background: The global incidence of persistent pain after surgery is approximately 10%, with considerable clinical and socioeconomic impacts. Despite identifying many risk factors in its development and the challenging management of the often neuropathic pain complaints, preoperative recognition of high-risk patients in various surgical populations using a standardized risk factor assessment questionnaire is lacking. This study evaluates the predictive value of a short holistic risk factor screening questionnaire as a first step in preventing and treating persistent pain in adults undergoing elective surgery. Methods: This prospective observational pragmatic trial will include 560 adults undergoing elective surgery. The primary endpoint is the evaluation of the predictive value of the screening questionnaire, including the optimal cut-off determination in terms of sensitivity and specificity for inclusion in a perioperative high-vigilance program. Secondary endpoints are postoperative pain (intensity and characterization using the NRS and DN4), postoperative analgesic usage, and well-being using the EQ-5D-5 L. To assess the performance of the designed screening questionnaire in the identification of psychosocial pain aspects, HADs, and STAI-trait are being surveyed. Additionally, the multidimensional pain inventory (MPI, part 1) is being used to assess the impact of pain on daily life in patients. Discussion: This pragmatic clinical trial will evaluate a short preoperative screening questionnaire to predict persistent postoperative pain after elective surgery in adults. Suppose high-risk patients could be identified earlier using this short preoperative holistic screening questionnaire. In that case, it might contribute to a more widespread implementation of standardized preoperative assessment and awareness for preventing persistent postoperative pain. Trial Registration: Local ethics committee: B3002022000112. ClinicalTrials.gov identifier: NCT05526976. Registered on: 02 September 2022. Start of recruitment: 22 December 2022. Trial Status: This paper is based on protocol version 4.0. The first patient was assigned to the research project on the 22 of December 2022. We anticipate including the last patient in October 2023 and plan to finalize the study by January 2024.

Large-scale real-life implementation of technology-enabled care to maximize hospitals' medical surge preparedness during future infectious disease outbreaks and winter seasons: a viewpoint.

Hospitals can be overburdened with large numbers of patients with severe infectious conditions during infectious disease outbreaks. Such outbreaks or epidemics put tremendous pressure on the admission capacity of care facilities in the concerned region, negatively affecting the elective program within these facilities. Such situations have been observed during the recent waves of the coronavirus disease pandemic. Owing to the imminent threat of a "tripledemic" by new variants of the coronavirus disease (such as the new Omicron XBB.1.16 strain), influenza, and respiratory syncytial virus during future winter seasons, healthcare agencies should take decisive steps to safeguard hospitals' surge capacity while continuing to provide optimal and safe care to a potentially large number of patients in their trusted home environment. Preparedness of health systems for infectious diseases will require dynamic interaction between a continuous assessment of region-wide available hospital capacity and programs for intensive home treatment of patients who can spread the disease. In this viewpoint, we describe an innovative, dynamic coupling system between hospital surge capacity and cascading activation of a nationwide system for remote patient monitoring. This approach was developed using the multi-criteria decision analysis methodology, considering previously published real-life experiences on remote patient monitoring.

Considerations on the Obstacles That Lead to Slow Recruitment in a Pain Management Clinical Trial: Experiences from the Belgian PELICAN (PrEgabalin Lidocaine Capsaicin Neuropathic Pain) Pragmatic Study.

Background: A qualitative evaluation study of the prematurely terminated PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) study was performed. The PELICAN study aimed to examine pain management for localized neuropathic pain (LNP), as epidemiological figures have shown a high percentage of LNP patients in Belgium. The study compared systemic and topical medications according to pain relief, adverse effects, and several measures of quality of life. Objective: Achieving better study patient recruitment through qualitative research. To investigate and determine the causes of the observed recruitment problems in the PELICAN study, pain centers involved in the study as well as nonrecruiting pain centers were included. Furthermore, it aimed to highlight the positive and negative lessons learned from the conducted study and the number of obstacles the team had to overcome. Methods: A qualitative study, using a mixed methods approach, was performed. Multiple pain centers in Belgium completed an online survey, after which a structured interview was conducted to elaborate the responses in more detail. The broad topics of these meetings were feedback about the study, reviewing survey answers, and actions undertaken to enhance recruitment. Results: Different factors contributed to the low recruitment rate in the PELICAN study, such as limited and late referral from the general practitioners to the Belgian pain centers, insufficient internal referrals from nonpain specialists, lack of specific expertise on LNP in some centers, scarcity of staff, limited reimbursement to administer complex analgesic schemes, overestimation of the patient population, and the reluctance of patients to participate in pain research. Additionally, shortcomings in the implemented study design and the need for more logistical investments were identified. Conclusion: The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies. Future studies could support this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase. Clinical Trials. This trial is registered with NCT03348735. EUDRACT number 2018-003617-17.

A low dose of three local anesthetic solutions for interscalene blockade tested by thermal quantitative sensory testing: a randomized controlled trial.

This randomized double-blind controlled trial compared the block characteristics of three low-dose local anesthetics at different roots in an ultrasound-guided interscalene block, using thermal quantitative sensory testing for assessing the functioning of cutaneous small nerve fibres. A total of 37 adults scheduled to undergo shoulder arthroscopy were randomized to receive 5 mL of either 0.5% levobupivacaine with and without epinephrine 1/200,000 or 0.75% ropivacaine in a single-shot interscalene block. Thermal quantitative sensory testing was performed in the C4, C5, C6 and C7 dermatomes. Detection thresholds for cold/warm sensation and cold/heat pain were measured before and at 30 min, 6, 10 and 24 h after infiltration around C5. The need for rescue medication was recorded. No significant differences between groups were found for any sensation (lowest P = 0.28). At 6 h, the largest differences in sensory thresholds were observed for the C5 dermatome. The increase in thresholds were less in C4 and C6 and minimal in C7 for all sensations. The analgesic effect lasted the longest in C5 (time × location mixed model P < 0.001 for all sensory tests). The time to rescue analgesia was significantly shorter with 0.75% ropivacaine (P = 0.02). The quantitative sensory findings showed no difference in intensity between the local anesthetics tested. A decrease in block intensity, with minimal changes in pain detection thresholds, was observed in the roots adjacent to C5, with the lowest block intensity in C7. A clinically relevant shorter duration was found with 0.75% ropivacaine compared to the other groups. Trial registration NCT 02691442.

Staff empowerment and engagement in a magnet® recognized and joint commission international accredited academic centre in Belgium: a cross-sectional survey.

BACKGROUND: A substantial number of studies linked aspects of a balanced, healthy and supportive nurse practice environment with quality and patient safety. To what extent balanced work characteristics such as social capital, decision latitude and workload are relevant for all staff engaged in patient care including healthcare and medical staff in a Magnet Recognized and Joint Commission International accredited academic centre is unclear. The study aim is to investigate associations between work characteristics such as social capital, decision latitude and workload, work engagement and feelings of burnout as explanatory variables and job satisfaction, turnover intentions and perceived quality of care as dependent variables in a study population of nursing, healthcare and medical staff taken in account generation differences. METHODS: Hierarchical regression analysis estimated strength of associations with demographic characteristics (block-1), professional category (block-2), work characteristics (block-3) and work engagement or burnout dimensions (block-4) as explanatory variables of job satisfaction and turnover intention and quality of care as outcome variables. RESULTS: The study confirmed and extended previous study findings demonstrating positive impact on staff' job outcomes and assessed quality of care by balanced work characteristics such as social capital, decision latitude and workload in nursing staff (N = 864), healthcare staff (N = 131) and medical staff (N = 241). Generational characteristics and professional category were associated with turnover intentions and less favorable assessed quality of care, respectively. Explained variances of studied models ranged from 14.4 to 45.7%. CONCLUSION: Engaging and committing staff to promote excellent patient outcomes in daily interdisciplinary practice works through clear frameworks, methods and resources supported by governance and policy structure that makes outcomes visible and accountable.

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex.

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and long-term consequences of unresolved pain or excessive analgosedation, adequate nociceptive monitoring remains challenging in non-communicative, critically ill adults. In the intensive care unit (ICU), routine nociceptive evaluation is carried out by the attending nurse using the Behavior Pain Scale (BPS) in mechanically ventilated patients. This assessment is limited by medication use (e.g., neuromuscular blocking agents) and the inherent subjective character of nociceptive evaluation by third parties. Here, we describe the use of two nociceptive reflex testing devices as tools for objective pain evaluation: the pupillary dilation reflex (PDR) and nociception flexion reflex (NFR). These measurement tools are non-invasive and well tolerated, providing clinicians and researchers with objective information regarding two different nociceptive processing pathways: (1) the pain-related autonomic reactivity and (2) the ascending component of the somatosensory system. The use of PDR and NFR measurements are currently limited to specialized pain clinics and research institutions because of impressions that these are technically demanding or time-consuming procedures, or even because of a lack of knowledge regarding their existence. By focusing on the two abovementioned nociceptive reflex assessments, this study evaluated their feasibility as a physiological pain measurement method in daily practice. Pursuing novel technologies for evaluating the analgesia level in unconscious patients may further improve individual pharmacological treatment and patient related outcome measures. Therefore, future research must include large well-designed clinical trials in a real-life environment.

Effects of Stellate Ganglion Block on Analgesia Produced by Cervical Paravertebral Block as Established by Quantitative Sensory Testing: A Randomized Controlled Trial.

Objective: To use quantitative sensory testing (QST) to assess whether a stellate ganglion block (SGB) modulates the analgesia induced by cervical paravertebral block (CPVB). Design: A prospective double-blind randomized controlled trial. Setting: Department of Anesthesia, Antwerp University Hospital, October 2011 to December 2015. Subjects: Twenty-eight adults scheduled for arthroscopy of a nonfractured shoulder were enrolled. Methods: Participants were randomly assigned to receive either single CPVB (5 mL of levobupivacaine 0.5%) or combined CPVB + SGB (5 mL and 3 mL of levobubivacaine 0.5%, respectively). The detection thresholds for cold/warm sensations and cold/heat pain were established using thermal QST on the C4-C7 dermatomes before local anesthetic infiltration and at 0.5, 6, 10, and 24 hours thereafter. Our primary outcome was the time course of QST thresholds for the different neurosensitive/nociceptive modalities. As secondary and tertiary outcomes, we evaluated the degree of motor block and the time to first administration of rescue analgesics. Results: We randomized 20 patients. There were no significant differences in the detection thresholds for the neurosensitive/nociceptive modalities, motor block, or timing for rescue analgesics between the groups (P = 0.15-0.94). All patients with CPVB + SGB exhibited Horner's signs, whereas patients in the CPVB group did not exhibit these signs; however, this does not exclude sympathetic block. Conclusions: We were unable to demonstrate any analgesic benefit of CPVB + SGB in arthroscopic shoulder surgery. It is therefore not unreasonable to suppose that pain from soft tissue injuries without bony lesions is transmitted mainly by somatic nerves with no or only minimal involvement of the sympathetic nervous system.

Implementation of an Enhanced Recovery Pathway for Minimally Invasive Pectus Surgery: A Population-Based Cohort Study Evaluating Short- and Long-Term Outcomes Using eHealth Technology.

BACKGROUND: Pectus excavatum and pectus carinatum are the most common chest wall deformities. Although minimally invasive correction (minimally invasive repair of pectus, MIRP) has become common practice, it remains associated with severe postoperative pain. Preoperative psychosocial factors such as anxiety and low self-esteem can increase postsurgical pain. Early detection of psychological symptoms, effective biopsychosocial perioperative management of patients, and prevention of pain chronification using an enhanced recovery pathway (ERP) may improve outcomes. However, the incidence of the latter is poorly described in adolescents undergoing MIRP. OBJECTIVE: The objective of our study was to evaluate the implementation of an ERP containing early recovery goals and to assess persistent postsurgical pain 3 months postoperatively in pediatric patients undergoing MIRP. The ERP consists of a Web-based platform containing psychological screening questionnaires and extensive telemonitoring for follow-up of patients at home. METHODS: A population-based cohort study was conducted with prospectively collected data from patients undergoing pectus surgery between June 2017 and December 2017. An ERP was initiated preoperatively; it included patient education, electronic health-based psychological screening, multimodal pre-emptive analgesia, nausea prophylaxis as well as early Foley catheter removal and respiratory exercises. After hospital discharge, patients were followed up to 10 weeks using a Web-based diary evaluating pain and sleep quality, while their rehabilitation progress was monitored via Bluetooth-connected telemonitoring devices. RESULTS: We enrolled 29 adolescents using the developed ERP. Pre-emptive multimodal analgesia pain rating scores were low at hospital admission. Optimal epidural placement, defined by T8-9 or T9-10, occurred in 90% (26/29) of the participants; thus, no motor block or Horner syndrome occurred. Mean bladder catheterization duration was 3.41 (SD 1.50) days in ERP patients. Numeric rating scale (NRS) scores for pain and the incidence of nausea were low, contributing to a fluent rehabilitation. Mean NRS scores were 2.58 (SD 1.77) on postoperative day (POD) 1, 2.48 (SD 1.66) on POD 2, and 3.14 (SD 1.98) on POD 3 in ERP-treated patients. Telemonitoring at home was feasible in adolescents after hospital discharge despite adherence difficulties. Although the pain scores at the final interview were low (0.81 [SD 1.33]), 33% (9/27) long-term follow-up ERP patients still experienced frequent disturbing thoracic pain, requiring analgesic administration, school absenteeism, and multiple doctor (re)visits. CONCLUSIONS: Allocating patients to the appropriate level of care preoperatively and immediately postoperatively may improve long-term outcome variables. Internet-based technologies and feasible, objective monitoring tools can help clinicians screen surgical patients for risk factors and initiate early treatment when indicated. Future research should focus on improving risk stratification and include a psychological assessment and evaluation of the effect of perioperative care pathways in children undergoing major surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03100669; https://clinicaltrials.gov/ct2/show/NCT03100669 (Archived by WebCite at http://www.webcitation.org/72qLB1ADX).

Thermal quantitative sensory testing to assess the sensory effects of three local anesthetic solutions in a randomized trial of interscalene blockade for shoulder surgery.

PURPOSE: This study investigated whether quantitative sensory testing (QST) with thermal stimulations can quantitatively measure the characteristics of an ultrasound-guided interscalene brachial plexus block (US-ISB). METHODS: This was a prospective randomized trial in patients scheduled for arthroscopic shoulder surgery under general anesthesia and US-ISB. Participants and observers were blinded for the study. We assigned the study participants to one of three groups: 0.5% levobupivacaine 15 mL, 0.5% levobupivacaine 15 mL with 1:200,000 epinephrine, and 0.75% ropivacaine 15 mL. We performed thermal QST within dermatomes C4, C5, C6, and C7 before infiltration and 30 min, six hours, ten hours, and 24 hr after performing the US-ISB. In addition, we used QST, a semi-objective quantitative testing method, to measure the onset, intensity, duration, extent, and functional recovery of the sensory block. We also measured detection thresholds for cold/warm sensations and cold/heat pain. RESULTS: Detection thresholds for all thermal sensations within the ipsilateral C4, C5, C6, and C7 dermatomes increased rapidly (indicating the development of a hypoesthetic state) and reached a steady state after 30 min. This lasted for approximately ten hours and returned to normal detection thresholds by 24 hr. There were no differences detected between the three groups at 24 hr when we compared warm sensation thresholds on one dermatome. Visual inspection of the pooled results per dermatome suggests the ability of QST to detect clinically relevant differences in block intensity per dermatome. CONCLUSIONS: Quantitative sensory testing can be useful as a method for detecting the presence and characteristics of regional anesthesia-induced sensory block and may be used for the evaluation of clinical protocols. The three local anesthetic solutions exhibited a similar anesthetic effect. The results support the use of QST to assess block characteristics quantitatively under clinical research conditions. This trial was registered at Clinicaltrals.gov, NCT02271867.

Chronic Constriction Injury of the Rat's Infraorbital Nerve (IoN-CCI) to Study Trigeminal Neuropathic Pain.

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral procedures to study trigeminal neuropathic pain in rats. To meet the specificity of trigeminal neuropathic pain syndromes, the infraorbital nerve (IoN) is subjected to a chronic constriction injury (CCI) by loosely ligating the nerve. An intra-orbital approach is presented here to expose and ligate the IoN in the orbital cavity. After IoN ligation, rats exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are indicative of persistent pain and mechanical allodynia. Two phases can be defined in the development of the behavioral changes. During the first week following IoN-CCI (phase 1), rats show an increased and asymmetric face grooming activity, i.e., with face wash strokes primarily directed to the nerve-injured IoN territory. A distinction is made between face grooming behavior that is part of a more general body grooming behavior, which remains largely unaffected by IoN-CCI, and face grooming that is neither preceded nor followed by body grooming, which is significantly increased after IoN-CCI. During this period, responsiveness to mechanical stimulation of the IoN territory is reduced. This hyporesponsiveness is abruptly replaced by an extreme hyperresponsiveness whereby even very weak stimulus intensities provoke nocifensive behavior (phase 2). The phenomenological similarities between these behavioral alterations and reported signs of facial pain (i.e., responses to noxious stimulation of the face) suggest the presence of dysesthesia/paresthesia and mechanical allodynia in the ligated IoN territory.

Cerebral activation during von Frey filament stimulation in subjects with endothelin-1-induced mechanical hyperalgesia: a functional MRI study.

Endothelin-1 (ET-1) is an endogenously expressed potent peptide vasoconstrictor. There is growing evidence that ET-1 plays a role in the pain signaling system and triggers overt nociception in humans. The underlying neuronal pathways are still a matter of great debate. In the present study, we applied an intradermal ET-1 sensitization model to induce mechanical hyperalgesia in healthy subjects. Functional magnetic resonance imaging (fMRI) was used to tease out the cortical regions associated with the processing of ET-1-induced punctate hyperalgesia, as compared to a nonnoxious mechanical stimulation of the contralateral arm. Von Frey hair testing revealed the presence of increased responsiveness to punctate stimulation in all subjects. Activational patterns between nonpainful control stimulation and hyperalgesic stimulation were compared. Two major observations were made: (1) all cortical areas that showed activation during the control stimulation were also present during hyperalgesic stimulation, but in addition, some areas showed bilateral activation only during hyperalgesic stimulation, and (2) some brain areas showed significantly higher signal changes during hyperalgesic stimulation. Our findings suggest that injection of ET-1 leads to a state of punctate hyperalgesia, which in turn causes the activation of multiple brain regions. This indicates that ET-1 activates an extended neuronal pathway.

Treatment of breakthrough cancer pain: to titrate or to proportionate?

Breakthrough cancer pain can be treated effectively by rapid-onset opioids, such as sublingual fentanyl. However, it remained unclear how the optimal dose of sublingual fentanyl should be determined. Dosing proportional to basic opioid regimen is now proposed as an alternative to dose titration.