Pore development in viscoelastic foods during drying.

In this paper, we present a numerical model that can describe the pore formation/cavitation in viscoelastic food materials during drying. The food material has been idealized as a spherical object, with a core/shell structure and a central gas-filled cavity. The shell represents a skin as present in fruits/vegetables, having a higher elastic modulus than the tissue, which we approximate as a hydrogel. The gas-filled pore is in equilibrium with the core hydrogel material, and it represents pores in food tissues as present in intercellular junctions. The presence of a rigid skin is a known prerequisite for cavitation (inflation of the pore) during drying. For modeling, we follow the framework of Suo and coworkers, describing the inhomogeneous large deformation of soft materials like hydrogels - where stresses couple back to moisture transport. In this paper, we have extended such models with energy transport and viscoelasticity, as foods are viscoelastic materials, which are commonly heated during their drying. To approach the realistic properties of food materials we have made viscoelastic relaxation times a function of Tg/T, the ratio of (moisture dependent) glass transition temperature and actual product temperature. We clearly show that pore inflation only occurs if the skin gets into a glassy state, as has been observed during the (spray) drying of droplets of soft materials like foods.

Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS.

PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment. MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms. RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity (P = .004). Having chronic pain conditions (P < .001), prior severe stent pain (P = .021), and depressive symptoms at baseline (P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms. CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

Long-Term Prescription Opioid Use After Injury in Washington State 2015-2018.

BACKGROUND: Patients with injury may be at high risk of long-term opioid use due to the specific features of injury (e.g., injury severity), as well as patient, treatment, and provider characteristics that may influence their injury-related pain management. OBJECTIVES: Inform prescribing practices and identify high-risk populations through studying chronic prescription opioid use in the trauma population. METHODS: Using the Washington State All-Payer Claims Database (WA-APCD) data, we included adults aged 18-65 years with an incident injury from October 1, 2015-December 31, 2017. We compared patient, injury, treatment, and provider characteristics by whether or not the patients had long-term (≥ 90 days continuous prescription opioid use), or no opioid use after injury. RESULTS: We identified 191,130 patients who met eligibility criteria and were included in our cohort; 5822 met criteria for long-term use. Most had minor injuries, with a median Injury Severity Score = 1, with no difference between groups. Almost all patients with long-term opioid use had filled an opioid prescription in the year prior to their injury (95.3%), vs. 31.3% in the no-use group (p < 0.001). Comorbidities associated with chronic pain, mental health, and substance use conditions were more common in the long-term than the no-use group. CONCLUSION: Across this large cohort of multiple, mostly minor, injury types, long-term opioid use was relatively uncommon, but almost all patients with chronic use post injury had preinjury opioid use. Long-term opioid use after injury may be more closely tied to preinjury chronic pain and pain management than acute care pain management.

The Prevalence and Factors Associated with the Prescription of Opioids for Head/Neck Pain after Elective Craniotomy for Tumor Resection/Vascular Repair: A Retrospective Cohort Study.

Background and objective: There is no report of the rate of opioid prescription at the time of hospital discharge, which may be associated with various patient and procedure-related factors. This study examined the prevalence and factors associated with prescribing opioids for head/neck pain after elective craniotomy for tumor resection/vascular repair. Methods: We performed a retrospective cohort study on adults undergoing elective craniotomy for tumor resection/vascular repair at a large quaternary-care hospital. We used univariable and multivariable analysis to examine the prevalence and factors (pre-operative, intraoperative, and postoperative) associated with prescribing opioids at the time of hospital discharge. We also examined the factors associated with discharge oral morphine equivalent use. Results: The study sample comprised 273 patients with a median age of 54 years [IQR 41,65], 173 females (63%), 174 (63.7%) tumor resections, and 99 (36.2%) vascular repairs. The majority (n = 264, 96.7%) received opioids postoperatively. The opiate prescription rates were 72% (n = 196/273) at hospital discharge, 23% (19/83) at neurosurgical clinical visits within 30 days of the procedure, and 2.4% (2/83) after 30 days from the procedure. The median oral morphine equivalent (OME) at discharge use was 300 [IQR 175,600]. Patients were discharged with a median supply of 5 days [IQR 3,7]. On multivariable analysis, opioid prescription at hospital discharge was associated with pre-existent chronic pain (adjusted odds ratio, aOR 1.87 [1.06,3.29], p = 0.03) and time from surgery to hospital discharge (compared to patients discharged within days 1−4 postoperatively, patients discharged between days 5−12 (aOR 0.3, 95% CI [0.15; 0.59], p = 0.0005), discharged at 12 days and later (aOR 0.17, 95% CI [0.07; 0.39], p < 0.001)). There was a linear relationship between the first 24 h OME (p < 0.001), daily OME (p < 0.001), hospital OME (p < 0.001), and discharge OME. Conclusions: This single-center study finds that at the time of hospital discharge, opioids are prescribed for head/neck pain in as many as seven out of ten patients after elective craniotomy. A history of chronic pain and time from surgery to discharge may be associated with opiate prescriptions. Discharge OME may be associated with first 24-h, daily OME, and hospital OME use. Findings need further evaluation in a large multicenter sample. The findings are important to consider as there is growing interest in an early discharge after elective craniotomy.

Patient and Provider Acceptability of a Patient Preauthorized Concealed Opioid Reduction.

OBJECTIVE: Limited research of how to best taper opioids brings about an ethical and clinical dilemma. Experiments using overt and concealed administration of opioids have demonstrated the benefits of a concealed reduction to eliminate negative expectations and prolong analgesic benefits. This may allow for opioid tapering without significant increases in pain. Based on this, we investigated patient and provider acceptance of a concealed opioid reduction for chronic pain. METHODS: We conducted a cross-sectional survey via REDcap with 74 patients, who are currently taking or have taken high dose opioids, and 49 providers using a validated questionnaire based on two hypothetical clinical trials comparing a patient preauthorized concealed opioid reduction vs standard tapering. RESULTS: We found that patients and providers have positive attitudes toward a concealed reduction of opioid dosages. More than 60% of providers and patients surveyed viewed the hypothetical clinical trial as helpful to reduce pain, side effects, and withdrawal symptoms. Sixty-one percent of patients and 77.6% of providers recognized that there would be differences in pain relief depending upon which group the hypothetical participants would be enrolled in. CONCLUSIONS: Patients and providers appear to understand the benefits of a concealed opioid reduction. Our findings support future randomized controlled trials that compare concealed and overt opioid tapering in patients with chronic pain. More research is needed to understand the difference in attitudes between research and clinical practice and to test the acceptability of a concealed reduction following a participation in an active clinical trial.

Common Biological Modulators of Acute Pain: An Overview Within the AAAPT Project (ACTTION-APS-AAPM Acute Pain Taxonomy).

OBJECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) project relies on the identification of modulators to improve characterization and classification of acute pain conditions. In the frame of the AAAPT effort, this paper presents an overview of common biological modulators of acute pain. METHODS: Nonsystematic overview. RESULTS: Females may experience more acute pain than males, but the clinical significance may be modest. Increasing age is associated with decreasing analgesic requirement and decreasing pain intensity after surgery and with higher risk of acute low back pain. Racial and ethnic minorities have worse pain, function, and perceived well-being. Patients with preexisting chronic pain and opioid use are at higher risk of severe acute pain and high opioid consumption. The OPRM1 gene A118G polymorphism is associated with pain severity and opioid consumption, with modest quantitative impact. Most studies have found positive associations between pain sensitivity and intensity of acute clinical pain. However, the strength of the association is unclear. Surgical techniques, approaches, and complications influence postoperative pain. CONCLUSIONS: Sex, age, race, ethnicity, preexisting chronic pain and opioid use, surgical approaches, genetic factors, and pain sensitivity are biological modulators of acute pain. Large studies with multisite replication will quantify accurately the association between modulators and acute pain and establish the value of modulators for characterization and classification of acute pain conditions, as well as their ability to identify patients at risk of uncontrolled pain. The development and validation of quick, bed-side pain sensitivity tests would allow their implementation as clinical screening tools. Acute nonsurgical pain requires more investigation.

Mutations affecting glycinergic neurotransmission in hyperekplexia increase pain sensitivity.

See Dickenson (doi:10.1093/brain/awx334) for a scientific commentary on this article.Inhibitory interneurons in the spinal cord use glycine and GABA for fast inhibitory neurotransmission. While there is abundant research on these inhibitory pain pathways in animal models, their relevance in humans remains unclear, largely due to the limited possibility to manipulate selectively these pathways in humans. Hyperekplexia is a rare human disease that is caused by loss-of-function mutations in genes encoding for glycine receptors and glycine transporters. In the present study, we tested whether hyperekplexia patients display altered pain perception or central pain modulation compared with healthy subjects. Seven patients with genetically and clinically confirmed hyperekplexia were compared to 14 healthy age- and sex-matched controls. The following quantitative sensory tests were performed: pressure pain detection threshold (primary outcome), ice water tolerance, single and repeated electrical pain detection thresholds, nociceptive withdrawal reflex threshold, and conditioned pain modulation. Statistical analysis was performed using linear mixed models. Hyperekplexia patients displayed lower pain thresholds than healthy controls for all of the quantitative sensory tests [mean (standard deviation)]: pressure pain detection threshold [273 (170) versus 475 (115) kPa, P = 0.003], ice water tolerance [49.2 (36.5) versus 85.7 (35.0) s, P = 0.015], electrical single pain detection threshold [5.42 (2.64) versus 7.47 (2.62) mA, P = 0.012], electrical repeated pain detection threshold [3.76 (1.41) versus 5.8 (1.73) mA, P = 0.003], and nociceptive withdrawal reflex [7.42 (3.63) versus 14.1 (6.9) mA, P = 0.015]. Conditioned pain modulation was significantly reduced in hyperekplexia [increase to baseline: 53.2 (63.7) versus 105 (57) kPa, P = 0.030]. Our data demonstrate increased pain sensitivity and impaired central pain modulation in hyperekplexia patients, supporting the importance of glycinergic neurotransmission for central pain modulation in humans.

Can quantitative sensory tests predict failed back surgery?: A prospective cohort study.

BACKGROUND: Failed back surgery syndrome (FBSS) is a pain condition refractory to therapy, and is characterised by persistent low back pain after spinal surgery. FBSS is associated with severe disability, low quality of life and high unemployment. We are currently unable to identify patients who are at risk of developing FBSS. Patients with chronic low back pain may display signs of central hypersensitivity as assessed by quantitative sensory tests (QST). This can contribute to the risk of developing persistent pain after surgery. OBJECTIVE: We tested the hypothesis that central hypersensitivity as assessed by QST predicts FBSS. DESIGN: Prospective cohort study. SETTING: Three tertiary care centres. PATIENTS: 141 patients scheduled for up to three segment spinal surgery for chronic low back pain (defined as at least 3 on a numerical rating scale on most days during the week and with a minimum duration of 3 months) due to degenerative changes. OUTCOMES: We defined FBSS as persistent pain, persistent disability or a composite outcome defined as either persistent pain or disability. The primary outcome was persistent pain 12 months after surgery. We applied 14 QST using electrical, pressure and temperature stimulation to predict FBSS and assessed the association of QST with FBSS in multivariable analyses adjusted for sociodemographic, psychological and clinical and surgery-related characteristics. RESULTS: None of the investigated 14 QST predicted FBSS, with 95% confidence intervals of crude and adjusted associations of all QST including one as a measure of no association. Results remained robust in all sensitivity and secondary analyses. CONCLUSION: The study indicates that assessment of altered central pain processing using current QST is unlikely to identify patients at risk of FBSS and is therefore unlikely to inform clinical decisions.

Driving water cavitation in a hydrogel cavity.

We study the dynamics of the dehydration process of a hydrogel with a cavity filled with water. We identify two transient phases: the first one dominated by an inflatable-balloon deformation mode, and the second by a suction effect, determining highly not homogeneous deformation modes of the hydrogel walls. This last phase triggers negative pressures into the cavity up to the typical values of water cavitation. An analysis of the factors allowing cavitation pressure to form inside the cavity is proposed, to allow for precise tuning of the key geometrical and material parameters.

Modeling and simulation of fish swimming with active muscles.

Our goal is to reproduce the key features of carangiform swimming by modeling muscle functioning using the notion of active distortions, thus emphasizing the kinematical role of muscle, the generation of movement, rather than the dynamical one, the production of force. This approach, already proposed to model the action of muscles in different contexts, is here tested again for the problem of developing an effective and reliable framework to model and simulate swimming. A proper undulatory movement of a fish-like body is reproduced by defining a pattern of distortions, tuned in both space and time, meant to model the muscles activation which produce the flexural motion of body fish; eventually, interactions with the surrounding water yields the desired thrust. Carangiform swimmers have a relatively inflexible anterior body section and a generally flat, flexible posterior section. Because of this configuration, undulations sent rearward along the body attain a significant amplitude only in the posterior section. We compare the performances of different swimming gaits, and we are able to find some important relations between key parameters such as frequencies, wavelength, tail amplitude, and the achieved swim velocity, or the generated thrust, which summarize the swimming performance. In particular, an interesting relation is found between the Strouhal number and the wavelength of muscles activation. We highlight the muscle function during fish locomotion describing the activation of muscles and the relation between the force production and the shortening-lengthening cycle of muscle. We found a great accordance between results and empirical relations, giving an implicit validation of our models.

Non-pharmacological interventions for alleviating pain during orthodontic treatment.

BACKGROUND: Pain is prevalent during orthodontics, particularly during the early stages of treatment. To ensure patient comfort and compliance during treatment, the prevention or management of pain is of major importance. While pharmacological means are the first line of treatment for alleviation of orthodontic pain, a range of non-pharmacological approaches have been proposed recently as viable alternatives. OBJECTIVES: To assess the effects of non-pharmacological interventions to alleviate pain associated with orthodontic treatment. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 6 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 9), MEDLINE Ovid (1946 to 6 October 2016), Embase Ovid (1980 to 6 October 2016) and EThOS (to 6 October 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a non-pharmacological orthodontic pain intervention to a placebo, no intervention or another non-pharmacological pain intervention were eligible for inclusion. We included any type of orthodontic treatment but excluded trials involving the use of pre-emptive analgesia or pain relief following orthognathic (jaw) surgery or dental extractions in combination with orthodontic treatment. We excluded split-mouth trials (in which each participant receives two or more treatments, each to a separate section of the mouth) and cross-over trials. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed risk of bias and extracted data. We used the random-effects model and expressed results as mean differences (MD) with 95% confidence intervals (CI). We investigated heterogeneity with reference to both clinical and methodological factors. MAIN RESULTS: We included 14 RCTs that randomised 931 participants. Interventions assessed included: low-level laser therapy (LLLT) (4 studies); vibratory devices (5 studies); chewing adjuncts (3 studies); brain wave music or cognitive behavioural therapy (1 study) and post-treatment communication in the form of a text message (1 study). Twelve studies involved self-report assessment of pain on a continuous scale and two studies used questionnaires to assess the nature, intensity and location of pain.We combined data from two studies involving 118 participants, which provided low-quality evidence that LLLT reduced pain at 24 hours by 20.27 mm (95% CI -24.50 to -16.04, P < 0.001; I² = 0%). LLLT also appeared to reduce pain at six hours, three days and seven days.Results for the other comparisons assessed are inconclusive as the quality of the evidence was very low. Vibratory devices were assessed in five studies (272 participants), four of which were at high risk of bias and one unclear. Chewing adjuncts (chewing gum or a bite wafer) were evaluated in three studies (181 participants); two studies were at high risk of bias and one was unclear. Brain wave music and cognitive behavioural therapy were evaluated in one trial (36 participants) assessed at unclear risk of bias. Post-treatment text messaging (39 participants) was evaluated in one study assessed at high risk of bias.Adverse effects were not measured in any of the studies. AUTHORS' CONCLUSIONS: Overall, the results are inconclusive. Although available evidence suggests laser irradiation may help reduce pain during orthodontic treatment in the short term, this evidence is of low quality and therefore we cannot rely on the findings. Evidence for other non-pharmacological interventions is either very low quality or entirely lacking. Further prospective research is required to address the lack of reliable evidence concerning the effectiveness of a range of non-pharmacological interventions to manage orthodontic pain. Future studies should use prolonged follow-up and should measure costs and possible harms.

Regional anesthesia in pain management.

PURPOSE OF REVIEW: The study focuses on neural blocks with local anesthetics in postoperative and chronic pain. It is prompted by the recent publication of several systematic reviews and guidelines. RECENT FINDINGS: For postoperative pain, the current evidence supports infusions of local anesthetics at the surgical site, continuous peripheral nerve blocks, and neuraxial analgesia for major thoracic and abdominal procedures. Ultrasound guidance can improve the performance of the blocks and different patient outcomes, although the incidence of peripheral nerve damage is not decreased. For chronic pain, the best available evidence is on nerve blocks for the diagnosis of facet joint pain. Further research is needed to validate diagnostic nerve blocks for other indications. Therapeutic blocks with only local anesthetics (greater occipital nerve and sphenopalatine ganglion) are effective in headache. A possible mechanism is modulation of central nociceptive pathways. Therapeutic nerve blocks for other indications are mostly supported by retrospective studies and case series. SUMMARY: Recent literature strongly supports the use of regional anesthesia for postoperative pain, whereby infusions at peripheral nerves and surgical site are gaining increasing importance. Local anesthetic blocks are valid for the diagnosis of facet joint pain and effective in treating headache. There is a need for further research in diagnostic and therapeutic blocks for chronic pain.

Central Sensitization and Pain: Pathophysiologic and Clinical Insights.

Central sensitization is an increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input. AIM: To explain how the notion of central sensitization has changed our understanding of pain conditions, discuss how this knowledge can be used to improve the management of pain, and highlight knowledge gaps that future research needs to address. METHODS: Overview of definitions, assessment methods, and clinical implications. RESULTS: Human pain models, and functional and molecular imaging have provided converging evidence that central sensitization occurs and is clinically relevant. Measures to assess central sensitization in patients are available; however, their ability to discriminate sensitization of central from peripheral neurons is unclear. Treatments that attenuate central sensitization are available, but the limited understanding of molecular and functional mechanisms hampers the development of target-specific treatments. The origin of central sensitization in human pain conditions that are not associated with tissue damage remains unclear. CONCLUSION: The knowledge of central sensitization has revolutionized our neurobiological understanding of pain. Despite the limitations of clinical assessment in identifying central sensitization, it is appropriate to use the available tools to guide clinical decisions towards treatments that attenuate central sensitization. Future research that elucidates the causes, molecular and functional mechanisms of central sensitization would provide crucial progress towards the development of treatments that target specific mechanisms of central sensitization.

Analytical and numerical solutions of pore formation in elastic food materials during dehydration.

In this paper, we describe a model for pore formation in food materials during drying. As a proxy for fruits and vegetables, we take a spherical hydrogel, with a stiff elastic skin, and a central cavity filled with air and water vapour. The model describes moisture transport coupled to large deformation mechanics. Both stress and chemical potential are derived from a free energy functional, following the framework developed by Suo and coworkers. We have compared Finite Volume and Finite Element implementations and analytical solutions with each other, and we show that they render similar solutions. The Finite Element solver has a larger range of numerical stability than the Finite Volume solver, and the analytical solution also has a limited range of validity. Since the Finite Element solver operates using the mathematically intricate weak form, we introduce the method in a tutorial manner for food scientists. Subsequently, we have explored the physics of the pore formation problem further with the Finite Element solver. We show that the presence of an elastic skin is a prerequisite for the growth of the central cavity. The elastic skin must have an elastic modulus of at least 10 times that of the hydrogel. An initial pore with 10% of the size of the gel can grow to 5 times its initial size. Such an increase in porosity has been reported in the literature on drying of vegetables, if a dense hard skin is formed, known as case hardening. We discuss that models as presented in this paper, where moisture transport is strongly coupled to large deformation mechanics, are required if one wants to describe pore/structure formation during drying and intensive heating (as baking and frying) of food materials from first principles.

Lumbar intervertebral disc degeneration in low back pain.

Intervertebral disc degeneration is characterized by deterioration in structural support that is potentially followed by stimulated neuronal ingrowth, and dysfunction of cellular physiology in the disc. Discogenic low back pain originates from nociceptors within the intervertebral disc or the cartilage endplate. This narrative review examines the mechanisms of disc degeneration, the association between degeneration and pain, and the current diagnosis and treatment of discogenic low back pain. Mechanisms of disc degeneration include dysregulated homeostasis of the extracellular matrix of the disc, altered spine mechanics, DNA damage, oxidative stress, perturbed cell signaling pathways, and cellular senescence. Although disc degeneration is more common in individuals with low back pain than in asymptomatic ones, degeneration occurs in a large proportion of asymptomatic individuals. Therefore, degeneration itself is not sufficient to trigger low back pain. Imaging and discography are common diagnostic tools of discogenic low back pain but have limited validity to diagnose discogenic pain. Most of current treatments options are not specific to discogenic pain but are unspecific treatments of low back pain of any origin. There is an urgent need to clarify and distinguish the molecular mechanisms of discogenic pain from mechanisms of disc degeneration that are not involved in nociception. Future research should make use of current methods to study molecular mechanisms of human pain in comprehensively and quantitatively phenotyped patients with low back pain, with the objective to identify molecular triggers of discogenic pain and determine the relationship between molecular mechanisms, pain, and patient-relevant outcomes.

Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial.

BACKGROUND: Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. METHODS: Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. DISCUSSION: This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Contribution of Hypersensitivity to Postureteroscopy Ureteral Stent Pain: Findings From Study to Enhance Understanding of Stent-associated Symptoms.

OBJECTIVE: To examine the relationships between preoperative hypersensitivity to pain and central sensitization, and postoperative ureteral stent pain after ureteroscopy (URS) for urinary stones. METHODS: Adults enrolled in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS) underwent quantitative sensory testing (QST) prior to URS and stent placement. Hypersensitivity to mechanical pain was assessed using a pressure algometer. Participants rated their pain intensity to pressure applied to the ipsilateral flank area and lower abdominal quadrant on the side of planned stent placement, and the contralateral forearm (control). Pressure pain thresholds were also assessed. Central sensitization was assessed by applying a pointed stimulator (pinprick) and calculating the temporal summation. Postoperative stent pain intensity and interference were assessed using PROMIS questionnaires. Data were analyzed using repeated-measures mixed-effects linear models. RESULTS: Among the 412 participants, the median age was 54.0years, and 46% were female. Higher preoperative pain ratings to 2 kg and 4 kg mechanical pressure to the ipsilateral flank and abdominal areas were associated with higher postoperative stent pain intensity with the stent in situ. Greater degree of central sensitization preoperatively, manifesting as higher temporal summation, was associated with higher postoperative pain intensity. Factors associated with preoperative hypersensitivity on QST included female sex, presence of chronic pain conditions, widespread pain, and depression. CONCLUSION: Hypersensitivity to pain and central sensitization preoperatively was associated with postoperative ureteral stent pain, suggesting a physiologic basis for stent symptom variation. QST may identify patients more likely to develop stent pain after URS and could inform selection for preventive and interventional strategies.

Mortality with concurrent treatment with gabapentin and opioids among people with spine diagnoses in the U.S. Medicare population: a propensity-matched cohort study.

IMPORTANCE: Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. Concurrent gabapentin and opioid prescriptions are commonly reported in retrospective studies of opioid-related overdose deaths. OBJECTIVE: To determine whether people who filled gabapentin and opioid prescriptions concurrently ('gabapentin + opioids') had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently ('TCAs/duloxetine + opioids'). We hypothesized that people treated with gabapentin + opioids would have higher mortality rates compared to people treated with TCAs/duloxetine + opioids. DESIGN: Propensity score-matched cohort study with an incident user, active control design. The median (maximum) follow-up was 45 (1093) days. SETTING: Population-based. PARTICIPANTS: Medicare beneficiaries with spine-related diagnoses 2017-2019. The primary analysis included those who concurrently (within 30 days) filled at least 1 incident gabapentin + at least 1 opioid or at least 1 incident TCA/duloxetine + at least 1 opioid. EXPOSURES: People treated with gabapentin + opioids (n=67,133) were matched on demographic and clinical factors in a 1:1 ratio to people treated with TCAs/duloxetine + opioids (n=67,133). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at any time. A secondary outcome was occurrence of a major medical complication at any time. RESULTS: Among 134,266 participants (median age 73.4 years; 66.7% female), 2360 died before the end of follow-up. No difference in mortality was observed between groups (adjusted hazard ratio (HR) and 95% confidence interval (CI) for gabapentin + opioids was 0.98 (0.90, 1.06); p=0.63). However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 (1.00, 1.04); p=0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (a) restricted to less than or = 30-day follow-up and (b) that required at least 2 fills of each prescription. CONCLUSIONS AND RELEVANCE: When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine. However, providers should be cognizant of a small increased risk of major medical complications among opioid users initiating gabapentin compared to those initiating TCAs or duloxetine.

Probabilistic model for individual assessment of central hyperexcitability using the nociceptive withdrawal reflex: a biomarker for chronic low back and neck pain.

BACKGROUND: The nociceptive withdrawal reflex (NWR) has been proven to be a valuable tool in the objective assessment of central hyperexcitability in the nociceptive system at spinal level that is present in some chronic pain disorders, particularly chronic low back and neck pain. However, most of the studies on objective assessment of central hyperexcitability focus on population differences between patients and healthy individuals and do not provide tools for individual assessment. In this study, a prediction model was developed to objectively assess central hyperexcitability in individuals. The method is based on statistical properties of the EMG signals associated with the nociceptive withdrawal reflex. The model also supports individualized assessment of patients, including an estimation of the confidence of the predicted result. RESULTS: up to 80% classification rates were achieved when differentiating between healthy volunteers and chronic low back and neck pain patients. EMG signals recorded after stimulation of the anterolateral and heel regions and of the sole of the foot presented the best prediction rates. CONCLUSIONS: A prediction model was proposed and successfully tested as a new approach for objective assessment of central hyperexcitability in the nociceptive system, based on statistical properties of EMG signals recorded after eliciting the NWR. Therefore, the present statistical prediction model constitutes a first step towards potential applications in clinical practice.