UMLS:C0681814

The study aims to identify clinical and genetic factors that increase the risk of developing opioid use disorder (OUD) in patients using prescription opioids (POs) for pain relief. The researchers are using an existing biobank with whole exome sequencing and array genotyping. Participants are enrolled into the health system biobank and then into a second study focusing on opioid medication use. Data is collected through self-report surveys and electronic health records, including clinical, prescription, and brain imaging data. The goal is to understand the genetic and non-genetic contributions to OUD.


UMLS:C0035173


UMLS:C0679646


UMLS:C1511726


UMLS:C0242402

The study investigates the reasons for preoperative opioid use in patients undergoing total hip and knee arthroplasty (THA and TKA). It was found that not all patients use opioids for pain at the surgical site, with many using them for combined reasons. This combined use was associated with long-term use, suggesting that nonsurgical pain partly drives persistent opioid use after surgery. The study suggests that future care should focus on pain and non-pain reasons for presurgical opioid use to create tailored postoperative opioid weaning plans.


UMLS:C0242402


UMLS:C3693657

The paper discusses the use of Pragmatic Clinical Trials (PCTs) to address the healthcare needs arising from chronic pain, opioid misuse, and the COVID-19 pandemic. The National Institutes of Health, Department of Defense, and Department of Veterans Affairs have formed a partnership, the Pain Management Collaboratory, to advance nonpharmacological approaches and integrated models of care for pain management. The partnership supports 11 large-scale, multisite PCTs in veteran and military health systems. The paper also discusses strategies for advancing pain management in active clinical settings.


UMLS:C3693657


UMLS:C0242933


UMLS:C3266352

The study found that among patients who were not using opioids at the time of surgery, those with a history of opioid use, especially continuous use, were more likely to continue using opioids three months after surgery. This was also true for patients with moderate to high alcohol use. The study included 1,249 patients, 4.3% of whom continued opioid use three months post-surgery.


UMLS:C0154530

Patients with history of continuous opioid use


UMLS:C0678277

Patients with moderate to high alcohol use


UMLS:C5392141

The study explores the impact of the COVID-19 pandemic on veterans with chronic pain who were part of a clinical trial focused on pain management. The pandemic disrupted pain management service delivery, leading to changes in how veterans received services or managed their pain symptoms. However, it also offered opportunities for resilience and personal growth as veterans reflected on their lives and personal goals. The pandemic also highlighted mental health issues, which should be addressed as part of a comprehensive pain management approach. The discussions during counseling sessions provided a unique opportunity to facilitate behavior change by focusing on resilience to motivate individuals with chronic pain to adapt and adopt positive behaviors and outlooks to improve their pain experience and quality of life.


UMLS:C5392141


UMLS:C0199393


UMLS:C1304803

The study found that patients who had been exposed to opioids before surgery consumed more opioids after surgery compared to those who had not been exposed. This increase was particularly significant among chronic users. The study also found that patients who had been exposed to opioids before surgery were more likely to refill their prescriptions after surgery. The study suggests that existing guidelines for postoperative opioid use may be sufficient for most patients, but may need to be adjusted for chronic users.


UMLS:C1563199


UMLS:C1304803


UMLS:C0204799

is associated with small increases after surgery


UMLS:C0043210

developed new persistent use after benign hysterectomy

The study aimed to identify the incidence and predictors of new persistent opioid use after benign hysterectomy among opioid-naïve women. The study found that 4.6% of women developed new persistent opioid use after the procedure. Factors that significantly increased the odds of new persistent use included younger age, southern geographic location, preoperative psychiatric and pain disorders, more than one perioperative prescription, mood disorder medication use, tobacco smoking, and surgical complications. The study also found that minimally invasive hysterectomy and more recent surgery year significantly decreased the likelihood of new persistent opioid use.


UMLS:C2874363

Preoperative psychiatric and pain disorders


UMLS:C1283820

decreased likelihood of new persistent use


UMLS:C1144884

The study investigates the cause of death among West Virginia Medicaid enrollees who were discharged from hospitalization due to infective endocarditis (IE), with a focus on those with and without opioid use disorder (OUD). The top three causes of death were accidental drug poisoning, mental and behavioral disorders due to polysubstance use, and cardiovascular diseases. The proportion of deaths among patients discharged after IE-related hospitalization increased seven times from 2016 to 2019 among the OUD deaths, and doubled among the non-OUD deaths. The increase was higher in those with an OUD diagnosis, indicating that OUD significantly impacts survival outcomes among IE patients. The study emphasizes the importance of timely delivery of medication for OUD treatment and harm reduction efforts to IE patients, especially during the COVID-19 pandemic.


UMLS:C0432277


UMLS:C5541642


UMLS:C0597696

The study explores the beliefs about opioid risk, protective factors, and behavioral functions of opioid misuse among American Indian youth and young adults living on or near a reservation. The study found that family played a significant role in the initiation of opioid use, but also in treatment and recovery. The study also highlighted the need for upstream prevention methods, including increased employment and after-school activities.


UMLS:C0015576


UMLS:C0814357


UMLS:C0021270

The study investigates the impact of prenatal opioid exposure on the brain development of infants. Using resting-state functional MRI, the study found significant differences in global brain network connectivity between infants exposed to opioids in the womb and healthy control infants. Four network components were significantly different, two of which were associated with maternal psychological factors. The study also found significant differences in intra-network graph metrics between the two groups. These findings suggest that prenatal opioid exposure is associated with alterations in global brain functional networks and these alterations are also associated with maternal mental health.


UMLS:C2114037


UMLS:C2825804


UMLS:C2114037

Neonatal opioid withdrawal syndrome (NOWS)

The study investigates the impact of prenatal opioid exposure (POE) on neonatal opioid withdrawal syndrome (NOWS) severity. Using resting-state functional magnetic resonance imaging (rs-fMRI), the study found altered thalamic functional connectivity in infants with POE compared to healthy infants. The severity of NOWS was found to be correlated with these alterations. The study suggests that future research could use this method to predict long-term neurodevelopmental outcomes in infants with POE.


UMLS:C0919692


UMLS:C0228307


UMLS:C0242402

The study aimed to estimate the prevalence of delayed dispensing of opioid prescriptions from surgeons and dentists, and to evaluate the impact of laws shortening the period between prescription writing and dispensing. Data from 2014 to 2019 showed that 0.9% of opioid prescriptions were dispensed more than 30 days after writing. A law in Minnesota that precluded opioid prescription dispensing more than 30 days after writing decreased delayed dispensing prevalence by 0.22 percentage points. The study suggests that policy makers could mitigate prescription opioid misuse associated with delayed dispensing by shortening the maximum period between writing and dispensing of opioid prescriptions.


UMLS:C0026183


UMLS:C0242170


UMLS:C0616023

The study compared the concordance of opioid prescription fulfillment data between Michigan's prescription drug monitoring program (PDMP) and a national pharmacy prescription database (Surescripts). The study found that the PDMP database was more reliable in detecting opioid fulfillment after surgery, capturing twice as many patients with persistent opioid use compared to Surescripts. The prevalence of persistent opioid use was 10.7% using PDMP data, 5.5% using Surescripts data only, and 11.7% using both data resources.


UMLS:C0876481


UMLS:C0616023


UMLS:C5234947

The study reveals a significant increase in infective endocarditis (IE) cases in West Virginia, primarily associated with injection drug use. Over five years, there was a six-fold increase in IE admissions. Patients with drug use-associated IE were younger, had longer hospital stays, higher rates of MRSA, psychiatric disorders, cardiac surgeries, and discharges against medical advice. Drug use was found to be an independent predictor of discharge against medical advice or in-hospital mortality.


MONDO:0000565


UMLS:C0242566

Methicillin-resistant Staphylococcus aureus (MRSA)


UMLS:C5234947

Discharge against medical advice/In-hospital mortality


UMLS:C0849826

The study examined the relationship between perioperative anxiety, pain, and opioid use in patients undergoing elective surgical procedures. It was found that anxiety and surgical site pain were highest on the day of surgery and declined over time. Patients with anxiety reported higher opioid use and increased surgical pain compared to those without anxiety. However, anxiety did not significantly mediate the relationship between pain and opioid use. The study concludes that anxiety is an independent risk factor for increased pain and opioid use after surgery.


UMLS:C0849826


UMLS:C0518695


UMLS:C0085671

The study aimed to develop a clinical tool to predict severe pain during wound dressing changes. The study found that three predictors were most useful for this tool: type of dressing, resting wound pain, and expected pain. Algorithms based on these predictors were developed, which can be used to predict patients likely to experience severe pain during a dressing change. This is the first study to systematically examine a comprehensive set of wound and patient predictors for their individual and collective associations with pain during dressing changes.


UMLS:C5574858


UMLS:C3266208


UMLS:C0241745


UMLS:C0578072


UMLS:C0043210

The study investigates the frequency of coprescribing opioids with skeletal muscle relaxants or benzodiazepines after implant-based breast reconstruction. It was found that 86.7% of women who underwent this procedure filled an opioid prescription. Among these, 27.7% filled prescriptions for opioids and benzodiazepines, 14.4% for opioids and skeletal muscle relaxants, and 2.4% for all three. Risk factors for coprescribing opioids and benzodiazepines included use of acellular dermal matrix, immediate reconstruction, and history of anxiety. Women who filled prescriptions for these combinations were significantly more likely to refill opioid prescriptions. The study suggests avoiding coprescribing of opioids with skeletal muscle relaxants due to the risks of sedation and potential for increased opioid use after surgery.


UMLS:C0043210


UMLS:C2826124


UMLS:C0242402


UMLS:C1564816

Summary not provided or could not be parsed.


UMLS:C0445965


UMLS:C0314621


UMLS:C0005865

The study examined the impact of a financial incentive introduced by Blue Cross Blue Shield of Michigan (BCBSM) to reduce opioid use after vasectomies. The incentive, known as modifier 22, was implemented on July 1, 2019. The study found that the percentage of men who filled opioid prescriptions after a vasectomy dropped significantly from 32.5% before the policy to 12.6% after its implementation. This represents a 61% relative reduction. No significant change was observed in the control group.


PR:000032683


UMLS:C0009932


UMLS:C0054377

The study investigates the efficacy of a novel compound, C781, a β-arrestin-biased antagonist at Protease-Activated Receptor-2 (PAR2), in managing protease-induced pain in mice. The compound was found to effectively prevent and reverse mechanical and spontaneous nociceptive behaviors in response to small molecule PAR2 agonists, mast cell activators, and neutrophil elastase. However, it was not effective in the carrageenan inflammation model. The study suggests that optimizing the pharmacokinetic properties of C781 could improve its in vivo efficacy.


UMLS:C0054377


UMLS:C0054377

could be optimized to improve in vivo efficacy


UMLS:C0021270

Neonatal abstinence syndrome (NAS) is a condition that infants develop due to withdrawal from in utero maternal drug exposure, particularly opioids. The Finnegan Score is used to monitor these infants, with a score of >8 indicating opioid exposure. Non-pharmacological treatments are the first line of management for all infants, regardless of their initial symptoms. However, if symptoms persist despite supportive care, pharmacological treatment is necessary and can be life-saving in severe cases.


UMLS:C0021270


UMLS:C0021270

The study found significant variation in the care and characteristics of infants with neonatal opioid withdrawal syndrome (NOWS) across different sites. This variation was observed in maternal-infant characteristics, infant management, and outcomes. The study found wide variation in the proportion of infants whose mothers received adequate prenatal care, medication-assisted treatment, and prenatal counseling. There was also variation in the proportion of infants with toxicology screening, those receiving pharmacologic therapy, secondary medications, and nonpharmacologic interventions. The length of stay and the proportion of infants discharged with their parents also varied across sites. The study concludes that this variation suggests not all infants are receiving efficient and effective care for NOWS.


UMLS:C0026591


UMLS:C1256370

The study evaluates the outcomes of infants with neonatal opioid withdrawal syndrome (NOWS) treated with secondary therapy of phenobarbital or clonidine, in combination with morphine. The results showed that infants treated with phenobarbital had a shorter length of hospital stay and shorter duration of morphine treatment than those treated with clonidine. However, infants were more likely to be discharged from the hospital on phenobarbital than clonidine. Further investigation is needed to determine if the benefits of shorter hospital stay and shorter duration of morphine therapy justify the possible neurodevelopmental consequences of phenobarbital use in infants with NOWS.


UMLS:C0949270


UMLS:C1256370


UMLS:C2939425

The paper discusses Neonatal Opioid Withdrawal Syndrome (NOWS), a condition affecting newborns born to mothers who consumed opioids during pregnancy. The standard approach to care for NOWS is not well-established, but nonpharmacologic treatment is usually the first line of management, with pharmacologic treatment added if necessary. Morphine and methadone are commonly used for pharmacologic treatment, but buprenorphine is emerging as a potential option based on its pharmacologic profile and results from initial clinical trials.


UMLS:C2092425


PUBCHEM.COMPOUND:644073


UMLS:C1541533

The study investigates the effects of the cannabinoid agonist CB-13 on pain in mice. It was found that CB-13 reduces inflammation-induced pain in a manner dependent on peripheral CB 1 receptors. However, repeated dosing led to tolerance and dependence, suggesting that it may engage central CB 1 receptors, leading to unwanted side effects. Therefore, while the analgesic effect of acute peripheral CB 1 receptor activation is promising, caution is advised in the therapeutic use of CB-13.


UMLS:C1541533


UMLS:C0242406

The study developed an automated pipeline using convolutional neural networks to segment lumbar intervertebral discs and characterize their biochemical composition. The methodology used MRI to combine deep learning-based segmentation, atlas-based registration, and statistical parametric mapping for voxel-based analysis of T1ρ and T2 relaxation time maps to characterize disc degeneration and its associated disability. The segmentation algorithm produced accurate, high-confidence segmentations of the lumbar discs. The imaging-based degenerative grades were strongly negatively correlated with T1ρ and T2, particularly in the nucleus. The study revealed significant differences in the relaxation maps between minimal/moderate versus severe disability.


UMLS:C1283643


UMLS:C2717759


UMLS:C0231170


CHEBI:59163

The study aimed to identify serum biomarkers that correlate with Modic changes (MC), which are vertebral endplate bone marrow lesions associated with chronic low back pain (cLBP). The researchers found that biomarkers related to the formation and degradation of type III and type IV collagen, key molecules in bone marrow fibrosis, correlated with the presence of MC. The bivariable model with the highest diagnostic value for MC in cLBP patients was PRO-C3 + C4M.


UMLS:C0009332


UMLS:C0009333


PR:000050129


UMLS:C0332985

The study used T2* mapping from ultrashort echo-time (UTE) magnetic resonance imaging (MRI) to evaluate the biochemical composition of the cartilage endplate (CEP) and its correlation with disc degeneration. The results showed that CEP T2* values were highest centrally and lowest posteriorly. In younger individuals with mild-to-moderate disc degeneration, low CEP T2* values were associated with more severe disc degeneration. However, in older individuals, CEP T2* values did not associate with disc degeneration. The study suggests that deficits in CEP composition, as indicated by low T2* values, associate with severer disc degeneration during the mild-to-moderate stages.


UMLS:C2700066


UMLS:C0336660

Ultrashort echo-time (UTE) magnetic resonance imaging (MRI)


UMLS:C0235048

assesses effectiveness of nonpharmacologic treatments for

The Defense Health Agency is conducting a Sequential Multiple-Assignment Randomization Trial for Low Back Pain (SMART LBP) to assess the effectiveness of nonpharmacologic treatments for chronic low back pain. The trial involves two treatment phases, with participants receiving either physical therapy or the Move2Health program in phase I. Nonresponders are then randomized to receive either a combination of Move2Health and physical therapy or the Mindfulness-Oriented Recovery Enhancement program in phase II. The primary outcome is measured using the Patient-Reported Outcomes Measurement Information System pain interference computer-adapted test score.


UMLS:C0679646


UMLS:C0086713

Move2Health program and Physical therapy


UMLS:C0086713

Mindfulness-Oriented Recovery Enhancement program


UMLS:C0681815

Patient-Reported Outcomes Measurement Information System pain interference computer-adapted test score


HP:0030776

Vertebral endplate bone marrow lesions (Modic changes, MC)

The study investigates the composition of vertebral endplate bone marrow lesions (Modic changes, MC) in patients with chronic low back pain (CLBP) using water-fat MRI. The bone marrow fat fraction (BMF) was measured in these patients and compared with asymptomatic controls. The results showed that the presence of MC coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC, while in MC 2, BMF was higher. The differences in BMF were larger in patients with greater disability and were not associated with pain. The study suggests that water-fat MRI can be used to measure BMF, which could be used for quantitative assessments of MC severity and progression.


UMLS:C0262872


NCBIGene:90427

Vertebral endplate bone marrow lesions (Modic changes, MC)


UMLS:C3655321

Bone marrow fat fraction (BMF) differences


UMLS:C3655321


UMLS:C1518418

The National Institute of Health (NIH) Back Pain Consortium (BACPAC) is conducting a trial to evaluate the effectiveness of three forms of virtual reality (VR) for patients with chronic lower back pain (cLBP). The trial will involve 360 patients who will be randomized into one of three VR programs: skills-based VR, distraction-based VR, and sham VR. The patients will be monitored for 12 weeks using patient-reported outcomes, wearable sensor data, and electronic health record data. The primary outcome will be the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference scale. Secondary outcomes will include PROMIS Anxiety, PROMIS Sleep Disturbance, opioid prescription data, and Pain Catastrophizing Scale Short Form.


UMLS:C0457949

Patients with chronic lower back pain (cLBP)


UMLS:C3877812

NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference scale


UMLS:C3873755

The study developed a deep learning algorithm to automatically extract the vertebral midline for frontal and lateral radiographs, addressing the limitations of current measurement methods for spinal deformities. The algorithm was validated using 20,118 pairs of full spine radiographs from 15,378 patients. The 3D dataset was used to describe global imbalance parameters and to build a statistical shape model to describe global spine shape variations in preoperative deformity patients. The method can identify patient subgroups with similar shape characteristics without relying on an existing shape classification system.


UMLS:C0182216


UMLS:C1253948


UMLS:C0871511


UMLS:C0448353

The study investigates the role of paraspinal musculature (PSM) in chronic low back pain (LBP) using conventional MRI and chemical shift encoding-based water-fat MRI (CSE-MRI). The study found that the fat fraction (FF) in PSM, measured by CSE-MRI, showed excellent agreement between readers and was significantly associated with Goutallier classification (GC) at all spinal levels. The study also found that FF and GC were significantly associated with pain scores. The study suggests that CSE-MRI may be useful in detecting early stages of PSM degeneration and could be used in further investigations of the role of PSM in chronic LBP.


UMLS:C0262872

Chemical shift encoding-based water-fat MRI (CSE-MRI)


UMLS:C0424679


UMLS:C0448353

The study uses hierarchical multiple factor analysis (hMFA) to analyze MRI data of paraspinal muscles (PSM) in relation to low back pain (LBP). The analysis found complex relationships between pain intensity and specific muscles and spinal levels. Subjects with high asymmetry between left and right lean muscle composition and differences between spinal segments PSM quality and structure are more likely to increase in pain after prolonged time in microgravity. Changes in PSM quality and structure between pre and post-spaceflight relate to increase in pain after prolonged microgravity. The study also confirms previous research on the association of CEP damage and LBP diagnosis.


UMLS:C0242688


UMLS:C3686783


UMLS:C0333575

The study investigates the spatial distribution of fat infiltration (FI) in the paraspinal muscles (PSMs) in relation to chronic low back pain (cLBP) and degenerative intervertebral disc (IVD) pathology. Using MRI scans of 40 cLBP patients and 21 controls, the researchers found that the distribution of FI differs according to symptoms and adjacent IVD pathology. The region of the multifidus muscle closest to the disc center of rotation was found to be most susceptible to FI in the presence of symptomatic IVD degeneration. The study suggests that the spatial distribution patterns of FI in the PSMs could serve as a potential diagnostic biomarker for cLBP.


UMLS:C0457949


MONDO:0011385

Degenerative intervertebral disc (IVD) pathology


UMLS:C0224319


UMLS:C0457949

The study aims to examine the effectiveness of a combined approach of physical therapy and mindfulness (MIND-PT) for post-surgical rehabilitation in patients undergoing lumbar surgery. The study will compare an enriched pain management (EPM) pathway that integrates physical therapy and mindfulness with usual-care pain management (UC). The primary outcome will be the pain impact, assessed with the Pain, Enjoyment, and General Activity (PEG) scale. The main secondary outcome will be the time to opioid discontinuation. The study is part of the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative, which aims to provide scientific solutions to the opioid crisis.


UMLS:C0949766


HP:0012531

Pain, Enjoyment, and General Activity (PEG) scale


UMLS:C0242402


UMLS:C5444372

The Back Pain Consortium (BACPAC) Research Program Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs include guidelines for the collection, reading/grading, and storage of images. The procedures are meant to improve understanding of pain mechanisms and facilitate patient phenotyping by standardizing MRI-based methods for non-invasive assessments of spinal pathologies. These procedures can be applied at other centers performing MRI acquisitions in patients with low back pain (LBP).


UMLS:C1443867


UMLS:C0917711


UMLS:C0695341

MRI acquisitions in patients with Low Back Pain (LBP)


UMLS:C0457949

The paper discusses the development of a personalized medicine algorithm for treating chronic low back pain (cLBP), a prevalent condition that significantly impacts quality of life. The Back Pain Research Consortium, part of the National Institutes of Health Helping to End Addiction Long-termSM (HEAL) Initiative, is conducting a clinical trial to identify the most effective treatments for individual patients or patient subgroups. Four treatments were selected based on the strength of evidence and magnitude of treatment effect: duloxetine, acceptance and commitment therapy, a classification-based exercise and manual therapy intervention, and a self-management approach.


UMLS:C1882265


UMLS:C0114463


UMLS:C3658321


UMLS:C4082302

Classification-based exercise and manual therapy intervention


UMLS:C0262675


MESH:D000069196

Summary not provided or could not be parsed.


UMLS:C0578570


UMLS:C5392064


MESH:D000069196


UMLS:C0583420

The study investigates the value of group visits for patients undergoing treatment for opioid use disorder (OUD) in primary care. The study involved 25 participants who were part of a weekly group visit at a family medicine clinic. The participants demonstrated several communication behaviors that supported recovery, including emotional support, probing about others' lives, venting, joking, and expressing gratitude. These behaviors fostered a sense of accountability, shared identity, and a supportive community. However, some behaviors like side conversations, tangential comments, and individual participants dominating group time could detract from the group experience. The study suggests that the group visit format may add unique value in supporting patients in their recovery.


UMLS:C0014093


UMLS:C0871703


UMLS:C1527374

The paper presents a systematic review of studies on Group-Based Opioid Treatment (GBOT), which combines buprenorphine/naloxone (B/N) prescribing with group counseling for opioid use disorder (OUD). The review included 10 full-text articles and 5 conference abstracts, but found that most were of low quality and none were designed to rigorously compare GBOT with other treatment approaches. While most studies reported on the feasibility and acceptability of GBOT, more research is needed to determine its efficacy.


UMLS:C1320105


UMLS:C0681814


UMLS:C1527374


UMLS:C0260173

The study aimed to test the feasibility and acceptability of a mind-body intervention called Mindful Awareness in Body-oriented Therapy (MABT) as an additional treatment to buprenorphine for individuals with opioid use disorder (OUD). The MABT protocol, which lasts for 8 weeks, teaches skills for interoceptive awareness to promote self-care and emotion regulation. The study found that it was feasible to recruit and retain participants, and the intervention was well-received. The group that received MABT showed an increase in interoceptive awareness skills, and participants reported satisfaction with the intervention and perceived benefits.


PUBCHEM.COMPOUND:644073


UMLS:C0234416


UMLS:C0876909

The study aimed to assess the appropriateness of a behavioral activation intervention delivered by Peer Recovery Coaches (PRCs) to reduce problematic substance use in individuals not engaged in care. The study was conducted in a community resource center in Baltimore, serving low-income and homeless clients with high rates of problematic substance use. The findings suggest that PRC-delivered behavioral activation could be acceptable and appropriate with suggested adaptations, including adding peer-delivered case-management and linkage to care, and tailoring the intervention to include activities that are accessible and feasible in the community.


UMLS:C2733064


UMLS:C0008942


UMLS:C0682651

The paper discusses the manipulation of interoceptive pathways to improve symptoms in various disorders. The primary focus is on the respiratory system, outlining different pathways that can be manipulated at neural, behavioral, and psychological levels to change the representation of and attention to interoceptive signals. This can improve functioning and adaptive behavior. Interventions can include neuromodulation of the vagus nerve, slow breathing, or mindfulness-based interventions. The framework can be applied to other physiological systems and future research may integrate interventions across multiple levels of manipulation or bodily systems.


UBERON:0001004


UBERON:0001759


UMLS:C4552487


UMLS:C0814263


UMLS:C1145171


UMLS:C2169145

The study investigates the effects of therapy dose and therapeutic alliance on opioid abstinence in youth with opioid use disorder (OUD). The participants were divided into two groups: one receiving 12 weeks of Buprenorphine/Naloxone (Bup-Nal) treatment and the other receiving up to 2 weeks of Bup/Nal detoxification. The results showed that participants in the Bup-Nal group attended more therapy sessions, had increased therapeutic alliance, and had less opioid use by week-12 compared to the detox group. The study found a "dose-response" effect of therapy on abstinence in youth OUD, suggesting that extended Bup-Nal treatment may enhance abstinence through a mechanism of therapy facilitation.


UMLS:C0680207


UMLS:C2460978


UMLS:C5557372

The study investigates the feasibility and acceptability of the Mindful Recovery OUD Care Continuum (M-ROCC), a 24-week mindfulness-based intervention (MBI) for adults with Opioid Use Disorder (OUD) who are prescribed buprenorphine/naloxone (B/N) treatment. The results show that M-ROCC is feasible and acceptable, with high retention rates at 4 and 24 weeks, and increased mindfulness levels correlated with the frequency of informal mindfulness practice. The study suggests that MBIs can be integrated into standard primary care Office-Based Opioid Treatment (OBOT) among a population with substantial trauma history.


UMLS:C0812167

The study evaluated the effectiveness of Mindfulness-Oriented Recovery Enhancement (MORE) as an additional treatment to methadone maintenance treatment (MMT) for individuals with opioid use disorder and chronic pain. The results showed that participants who received MORE along with their usual MMT had significantly fewer days of illicit drug use, lower levels of craving, pain, physical and emotional limitations, depression, and anxiety compared to those who only received MMT. They also reported higher levels of well-being, vitality, and social functioning. The study suggests that MORE could be an effective addition to MMT.


UMLS:C0812167


UMLS:C1960643

The study investigates the role of stigma in the retention of patients in Medication for Opioid Use Disorder (MOUD) programs, particularly within ethno-racial minority communities. It suggests that Peer Recovery Specialists (PRSs), who have personal experience with substance use and recovery, could help reduce stigma-related barriers to MOUD retention. The study collected feedback from patients receiving methadone treatment and found that stigma, both internalized and anticipated, was a significant barrier to treatment. The PRS role, with its shared lived experience, was identified as a potential means to shift these stigma-related barriers.


UMLS:C0277787


UMLS:C0557536


UMLS:C0030705


UMLS:C5550174

The study investigates the feasibility and acceptability of a mobile digital therapeutic tool, reSET-O, in treating opioid use disorder. The tool, which delivers cognitive behavioral therapy modules and rewards for completion of modules and negative drug tests, was tested on 15 individuals undergoing buprenorphine treatment. The results showed that reSET-O was well received by both patients and providers, with patients finding it easy to use and helpful in providing a safe space to admit recurring substance use. However, adherence and retention in treatment were identified as areas for improvement.


UMLS:C4273841


UMLS:C1138603


UMLS:C3508320

The paper discusses the role of misinformation, misconceptions, and stigma in the low uptake of treatment for opioid use disorder. It highlights that these factors are prevalent among healthcare providers, first responders, pharmaceutical companies, and individuals with opioid use disorder. The paper suggests that social media, education, and community involvement can help mitigate these issues and improve understanding of opioids and treatment options.


UMLS:C0277787

negatively affects treatment uptake and adherence


UMLS:C1292796

Misconceptions about treatment efficacy and side effects


UMLS:C3179065


UMLS:C0679740

The study aimed to test the effectiveness of a peer recovery specialist-delivered behavioral activation and problem-solving approach (Peer Activate) in improving methadone retention among patients with opioid use disorder (OUD). The results showed that the intervention was feasible, acceptable, and implemented with high fidelity. The intervention group had a higher methadone retention rate, better methadone adherence, and a significant reduction in substance use frequency and substance use-related problems compared to a comparison cohort. The study suggests that the Peer Activate approach could be significant in promoting methadone retention, especially among vulnerable populations.


UMLS:C0679740


UMLS:C4324621


UMLS:C4505046

The study investigates the effects of a 24-week trauma-informed program called Mindful Recovery OUD Care Continuum (M-ROCC) on patients undergoing buprenorphine treatment for opioid use disorder. The findings suggest that the program reduces pain, anxiety, and substance use, including cocaine and benzodiazepines. The program also increased mindfulness, interoceptive awareness, and self-compassion among participants. The study concludes that larger randomized controlled trials are needed to confirm these findings.


UMLS:C4505046


UMLS:C4095868

The study explores the feasibility of conducting a 24-hour hackathon to develop solutions for the opioid crisis. The hackathon brought together teams from various fields such as law enforcement, public health, and data science. The event was planned with the help of an advisory board and planning committee, including key stakeholders. The participants were primarily from the industry, academia, public health/medicine, and government/public policy. The study found that it is feasible to implement such an event and recruit participants from a broad range of disciplines.


UMLS:C0871489


UMLS:C0162458


UMLS:C0679646


UMLS:C0339223

The study aimed to find an objective diagnostic sign to identify patients with neuropathic corneal pain (NCP), a condition often difficult to differentiate from conventional dry eye disease (DED). Using in vivo confocal microscopy (IVCM), the researchers found a decrease in total nerve density in both NCP and DED patients compared to healthy controls. However, microneuromas (terminal enlargements of subbasal corneal nerve) were observed in all patients with NCP, but not in any of the patients with DED. This suggests that microneuromas could serve as a sensitive and specific biomarker for the diagnosis of NCP.


UMLS:C5197850


UMLS:C5575281


UMLS:C1531708


UMLS:C0494081


UMLS:C1314200


CHEBI:24261

The study investigates the effects of glucocorticoids (GC), specifically methylprednisolone (MP), on the immune response in patients after major surgery. The results show that MP significantly alters immune cell signaling, particularly in the adaptive compartments of the immune system. However, key innate signaling responses associated with pain and recovery after surgery are not affected by MP. This suggests that GCs have cell-specific and pathway-specific effects.


UMLS:C1527312


UMLS:C1450464

The study investigates the effectiveness and tolerability of the tricyclic antidepressant, nortriptyline, in treating neuropathic corneal pain (NCP). The study included patients with clinically diagnosed NCP and a centralized component of pain, who were treated with oral nortriptyline. The results showed that nortriptyline was effective in relieving NCP symptoms in patients who tolerated the drug for at least 4 weeks. The mean ocular pain improved significantly and the quality of life also improved. However, some patients discontinued treatment due to persistent side effects.


UMLS:C1450464


PUBCHEM.COMPOUND:5360515

The study found that low-dose naltrexone (LDN) is effective and well-tolerated in treating neuropathic corneal pain (NCP), a condition caused by damage or disease of the somatosensory nervous system that innervates the cornea. The study involved 59 NCP patients who were treated with LDN for at least four weeks. The results showed a significant decrease in mean pain score and an improvement in quality of life scores. Common side effects included vivid dreams, headaches, and stomachache.


PUBCHEM.COMPOUND:5360515


UMLS:C0030705

The study reveals that patients with neurotrophic keratopathy (NK), a condition typically thought to lack discomfort symptoms, may experience ocular pain. A subset of these patients may also present with neuropathic corneal pain (NCP). The study involved 7 stage 1 NK patients who presented with concurrent ocular pain. The findings showed significant decrease in nerve densities in ranges consistent with NK as compared to normal controls, increased dendritiform cell density in three patients, and the presence of microneuromas in six of the patients. The study suggests that nerve damage and inflammation, which contribute to the development of NK, may result in chronic ocular pain, such as NCP, leading to potential underdiagnosis of either disease.


UMLS:C1408627


UMLS:C0030705


UMLS:C0035173

The study developed a classification system for chronic pain using symptoms rather than illness manifestations. The system was developed using a cohort of real-world patients who completed a multidimensional patient-reported registry. Hierarchical clustering was applied to a subset of patients using nine pain-agnostic symptoms. The system was validated using a three-cluster solution reflecting a graded scale of severity across all symptoms and eight independent pain-specific measures. Negative affect-related factors were key determinants of cluster assignment. The system promises to improve clinical care and provide markers for personalized diagnosis and prognosis.


UMLS:C0035173


UMLS:C0008902


UMLS:C0420256

The study investigates the effects of placebo administration on immune mechanisms and its relationship with endogenous opioid neurotransmission. The study involved 37 healthy human volunteers who were exposed to a standardized pain challenge and were given a placebo under the expectation of analgesia. The results showed that the placebo reduced the levels of plasma IL-18, a pro-inflammatory cytokine, during pain, and this reduction correlated with a reduction in pain scores. The reduction in IL-18 also correlated with placebo-induced endogenous opioid release in the left nucleus accumbens and left amygdala. These findings suggest that placebo administration can modulate the levels of a potent pro-inflammatory cytokine and its relationship with endogenous opioid activity.


UMLS:C0420256


PR:000001376


MONDO:0024317

The study titled "Signature for Pain Recovery IN Teens (SPRINT)" aims to discover and validate a prognostic signature for chronic musculoskeletal pain in adolescents. The study will collect and analyze a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging, and biological information over 12 months. The goal is to create a multivariate model with strong prognostic power regarding the clinical course of adolescent musculoskeletal pain and function. The study complies with the National Institutes of Health policy on the use of a single internal review board for multisite research.


UMLS:C0681814


UMLS:C2960026

The study evaluated the reliability of two potential biomarkers for pain: peak alpha frequency (PAF) and corticomotor excitability (CME). Participants were given an injection of nerve growth factor (NGF) into the right masseter muscle, inducing sustained pain. PAF and CME were then assessed using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) respectively. The study found that PAF was reliable even in the presence of pain and that 80% of individuals showed either facilitation or depression of CME, with these changes being stable across sessions. The study supports the reliability of PAF and CME as prospective cortical biomarkers for pain.


UMLS:C2210335


UMLS:C0030705

The study investigates the use of clinical questionnaires to predict the improvement of post-traumatic headaches (PTH) in patients who have suffered mild traumatic brain injury (mTBI). The study found that these questionnaires, which assess factors such as headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use, have good utility for predicting headache improvement at 3 and 6 months, as well as the evolving headache trajectory. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub-domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State-Trait Anxiety Inventory score.


UMLS:C0199186


UMLS:C0205451


UniProtKB:Q99VQ4

The study investigates the safety and efficacy of the isolated enzymatic A1 domain of LT (LTA1) as an adjuvant in intranasal influenza vaccines. The results show that LTA1 does not exhibit neurotoxicity, unlike cholera toxin. When used in vaccination, LTA1 enhances immune responses to inactivated virus antigen and improves protection against H1N1 influenza in mice. This enhanced protection was also observed in mice lacking B-cells, suggesting that the mechanism does not require B-cells.


UniProtKB:Q99VQ4


UMLS:C1279755


UMLS:C0042209

The study presents the development and testing of a novel vaccine against fentanyl, a potent opioid. The vaccine is composed of a fentanyl hapten conjugated to tetanus toxoid (TT) and adjuvanted with liposomes containing monophosphoryl lipid A adsorbed on aluminum hydroxide. The vaccine induced high and robust antibody endpoint titers in mice, and the antisera bound fentanyl and its analogues in vitro. The vaccine did not cross-react with other opioids like naloxone, naltrexone, methadone, or buprenorphine. In vivo, the vaccine shifted the antinociceptive dose-response curve of fentanyl to higher doses, indicating its potential to combat fentanyl-induced effects.


UMLS:C1875294


UMLS:C0042209


CHEBI:76107

The paper discusses the synthesis of a deuterated hapten, 6-AmHap, which is crucial for the study of residual hapten and stability of a hapten-protein conjugate. This hapten is selected for a heroin vaccine that is now ready for a Phase 1 clinical trial. The vaccine, which uses a maleimide-thiol bioconjugation strategy, connects the hapten 6-AmHap with an immunogenic carrier protein (tetanus toxoid, TT) through a trityl-protected 3-mercaptopropanamide linker. The antibodies induced by the vaccine have been found to be active against several opioids, including heroin and its metabolites, but do not affect alternate pain treatment medications such as methadone. The deuterated 6-AmHap was synthesized from hydrocodone.


PUBCHEM.COMPOUND:5284569


UMLS:C0042209

The study investigates the use of a vaccine targeting fentanyl, a major contributor to substance use disorder-related overdose deaths. The vaccine uses fentanyl-based haptens and is delivered either intramuscularly, sublingually, or intranasally with adjuvants derived from the heat-labile toxin of E. coli. The results show that the vaccine, especially when delivered sublingually or intranasally with dmLT or LTA1 adjuvants, produces high levels of anti-fentanyl antibodies and effectively blocks fentanyl-induced analgesia and CNS penetration. The study suggests that these delivery and adjuvant strategies may improve the efficacy of vaccines against substance use disorders.


UMLS:C3850135

The study explores the synthesis of three novel opiate surrogates (1, 2, and 3) as potential haptens for a heroin vaccine. These haptens were tested in mice for their immunogenicity and efficacy. All three haptens resulted in antibody endpoint titers of >105. However, none of the haptens induced antibodies with broad enough selectivity to recognize and bind heroin, 6-AM, and morphine, resulting in little to no protection against the antinociceptive effects of heroin in vivo. Only the mice immunized with hapten 3 were partially protected against heroin-induced antinociception. The results highlight the importance of rational hapten design for heroin vaccine development.


UMLS:C3850135


NCBIGene:4280


UMLS:C1273046


UMLS:C4543600

The study investigates the impact of preexisting immunity to tetanus toxoid on the efficacy of a heroin vaccine (TT-6-AmHap) in mice. The mice were first primed with a diphtheria, tetanus, and acellular pertussis (DTaP) vaccine, then immunized with the heroin vaccine. The results showed that preexisting immunity to tetanus toxoid did not affect the immunogenicity and efficacy of the heroin vaccine.


UMLS:C0003250

The study presents the development of chimeric monoclonal antibodies (mAb) that can specifically bind with fentanyl and its analogs, preventing them from reaching the central nervous system. This mAb-based passive immunotherapy does not interfere with other medications used to treat opioid use disorder (OUD). The study found two mAb candidates with high binding affinities to fentanyl and its analogs that were effective in engaging fentanyl in the periphery and blocking its effects in animals. This discovery is a significant contribution to the development of novel therapeutics targeting OUD.


UMLS:C0003250


PUBCHEM.COMPOUND:3345


MESH:D000485

The study presents the design and synthesis of four haptens, which are potential medications for opioid use disorder. These haptens are hydrolytically stable surrogates of heroin, attached at the C1 position in the 4,5-epoxymorophinan nucleus. The haptens were conjugated with tetanus toxoid (TT) and tested for their efficacy in vivo. All TT-hapten conjugates induced high antibody endpoint titers against the targets, but only haptens 2 and 3 showed protective effects against heroin in vivo. The study also found that the chirality at C6 in these epoxymorphinans is crucial to their effectiveness.


MESH:C520103


CHEBI:74818


PUBCHEM.COMPOUND:649923


UMLS:C1184301

The study investigates the impact of peripheral nerve injury on the lumbar sympathetic ganglion in two rat pain models. The models used were ligation of the L5 spinal nerve and local inflammation of the L5 dorsal root ganglion (DRG). Both models showed neuroinflammatory changes in the sympathetic ganglia, including macrophage responses, satellite glia activation, and increased numbers of T cells. There were also slight increases in sympathetic neuron excitability. The spinal nerve ligation model generally caused larger responses than DRG inflammation.


UMLS:C5230021


UBERON:0002859


UMLS:C1720269


MONDO:0043797

The study investigates the role of immune responses in the development of neuropathic pain following spinal cord injury (SCI). It was found that rats with SCI-induced pain had greater microglial activation in the dorsal horn and an increased number of macrophages in the dorsal root ganglia (DRG). Early exercise after SCI was found to reduce pain development, possibly by modulating the injury-induced macrophage response in the DRG. The presence of macrophages in the DRG may be a potential target for future pain therapies.


UMLS:C1882864


UMLS:C0237919


CL:0009048


PUBCHEM.COMPOUND:4829

The study investigates the role of sex in the development and treatment of central neuropathic pain in spinal cord injury (SCI). Using a mouse model, the researchers tested the analgesic efficacy of pioglitazone and azithromycin. The results showed a sex-specific effect of pioglitazone, with significant pain relief in female mice but not in males. Azithromycin, however, was effective in both sexes. The findings support the use of these drugs for SCI pain and emphasize the need to consider sex as a biological variable in SCI pain research.


PUBCHEM.COMPOUND:447043


UMLS:C1522384


UMLS:C1290885

The study investigates the role of calcium permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) in chronic pain. The research found that acute inflammation triggers the accumulation of these receptors in the spinal cord, which coincides with signs of acute inflammatory pain. The study also found that the CP-AMPAR antagonist IEM-1460 inhibited AMPAR-evoked Ca2+ transients after injury but had no effect in uninflamed mice. The study concludes that CP-AMPAR inhibitors could be a promising treatment for chronic inflammatory pain.


MESH:C406748


PUBCHEM.COMPOUND:5360515


MESH:C000718808


PR:000033575

The study investigates the properties of the DOP-KOP heteromer agonist, 6'-guanidinonaltrindole (6'-GNTI), in comparison with agonists for DOP and KOP in peripheral sensory neurons. All three agonists inhibited PGE2-stimulated cAMP accumulation and activated ERK with similar efficacy. However, the ERK activation by DPDPE or 6'-GNTI was Gi-protein independent. In vivo, all three agonists reduced thermal nociception. The antinociceptive responses to DPDPE or U50488 were transient but could be prolonged with inhibitors of 12/15-lipoxgenases (LOX). Responsiveness to 6'-GNTI remained for a prolonged time in the absence of LOX inhibitors. The results suggest that DOP-KOP heteromers may be a promising therapeutic target for the treatment of pain.


MESH:C507819


PR:000033575


UMLS:C3847834

The study investigates the role of Methylglyoxal (MG) in Painful Diabetic Neuropathy (PDN) in type 2 diabetes using db/db mice. The study found that MG and a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in these mice. The administration of a MG scavenger or a vector overexpressing glyoxalase 1, the enzyme that breaks down MG, reduced heat hypersensitivity in the mice. The study suggests that MG scavengers, glyoxalase inducers, and inhibitors of the MG-TRPA1-AC1-Epac pathway could be potential treatments for PDN in type 2 diabetes.


MESH:C000716787


UMLS:C0066384


GO:0086097


MESH:D063388

The paper discusses the role of endocannabinoids, a type of neurotransmitter system, in providing short-term pain relief following spinal manipulative therapy. The research suggests that understanding the involvement of endocannabinoids in this therapy could enhance its clinical efficacy.


UMLS:C2073787


MESH:D063388


UMLS:C5200744

The study presents a pH-responsive nanoparticle designed to target acidified endosomes and inhibit endosomal signalling events that lead to chronic pain. The nanoparticle enters cells and accumulates in endosomes containing the neurokinin 1 receptor (NK1R), which in chronic pain, redistributes from the plasma membrane to these endosomes. The nanoparticle contains the FDA-approved NK1R antagonist aprepitant, which inhibits the activation of spinal neurons and prevents pain transmission. The treatment provides complete and persistent relief from various types of pain and offers a non-opioid treatment option for chronic pain.


PUBCHEM.COMPOUND:135413536


UMLS:C5205585


UMLS:C0815002

Glutamatergic neurons in the parafascicular nucleus (GluPF)

The study identifies a neural pathway involving GABAergic neurons from the central nucleus of the amygdala (GABACeA) projecting to glutamatergic neurons in the parafascicular nucleus (GluPF), which then relay to neurons in the second somatosensory cortex (S2). This pathway is found to be inhibited in mice exhibiting symptoms of comorbid pain in depression (CP). The study suggests that reversing this pathway using chemogenetic or optogenetic approaches can alleviate CP symptoms.


CL:4023012

Glutamatergic neurons in the parafascicular nucleus (GluPF)

Neurons in the second somatosensory cortex (S2)


RHEA:12921


UMLS:C3665472


UMLS:C3494301


UMLS:C1167250

The paper discusses the role of lipid rafts in glial cells, specifically their role in neuroinflammation and pain processing. The researchers introduce the concept of an "inflammaraft", which are enlarged lipid rafts that contain activated receptors and adaptor molecules, and initiate inflammatory signaling and cellular response. The study suggests that targeting these inflammarafts could lead to new therapies for neuropathic pain and other neuroinflammatory conditions.


NCIT:C3137


UMLS:C1302375


GO:1903074


HP:0012531

The study investigates the relationship between pain, opioid use, and the role of GluA1 in the central amygdala (CeA). In a rat model, short-term pain was found to decrease voluntary morphine intake, but this effect was blocked by pre-treatment with a non-opioid pain inhibitor. The protein level of GluA1 was found to increase in rats with steady morphine self-administration (MSA), while GluA2 decreased, leading to an increased GluA1/GluA2 ratio in the CeA. Pain, however, decreased this ratio. Inhibiting GluA1-AMPARs in the CeA reduced morphine intake, while overexpressing GluA1 protein maintained a higher level of morphine intake and reversed the pain-induced reduction. This suggests that GluA1 in the CeA promotes opioid use and its upregulation can increase opioid consumption, counteracting the inhibitory effect of pain.


PUBCHEM.COMPOUND:3715


PR:000008233


UMLS:C1372573


NCBIGene:4897

The study investigates the role of alternative splicing of the Nrcam gene in neuropathic pain. Two splicing variants of Nrcam, Nrcam+10 and Nrcam-10, were found to be differentially expressed in the injured dorsal root ganglions (DRGs) after spinal nerve ligation in mice. The study found that an increase in Nrcam+10 and a decrease in Nrcam-10 contributed to neuropathic pain. An antisense oligonucleotide (ASO) that targeted exon 10 of the Nrcam gene was able to repress the expression of Nrcam+10 and increase the expression of Nrcam-10, thereby attenuating the development of neuropathic pain. The study concludes that targeting Nrcam alternative splicing could be a potential avenue for neuropathic pain management.


NCBIGene:4897


UMLS:C0078976


UMLS:C0597437

alleviate symptoms in half of the patients

The study discusses the role of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathophysiology. It highlights the development and clinical testing of drugs targeting CGRP or its receptor, which have been found to alleviate migraine symptoms in half of the patients. The study also suggests that a second CGRP receptor could be a new therapeutic target. The safety profile of CGRP-targeting drugs is attributed to the redundancy of peptides within the CGRP family and the nature of peptide release. The study supports the development of more refined CGRP therapeutic drugs and drugs that target other neuropeptides.


UMLS:C0108066


UMLS:C0597437


UMLS:C1531810


UMLS:C0079189

The study explores the role of cytokines, soluble mediators, in the development and maintenance of pain states. Cytokines are found to facilitate nociceptive processing at all levels of the neuraxis, leading to an enhanced pain state. This understanding of the interaction between neural and immune signaling systems in pain phenotypes could be key in understanding the induction of pain and the maintenance of facilitated states of pain behavior generated by tissue injury/inflammation and nerve injury.


UMLS:C0079189


UBERON:0001016


UMLS:C0262593

The study found that peripheral nerve injury led to an increase in the expression of long noncoding RNA H19 in the dorsal root ganglion (DRG). The use of a specific H19 siRNA in the injured DRG before and after nerve injury reduced symptoms of neuropathic pain such as mechanical allodynia and thermal hyperalgesia. The study suggests that H19 plays a role in the development and maintenance of neuropathic pain and could be a potential target for treatment.


MESH:C094335


MONDO:0700057


PR:000008233

The study investigates the role of GluA1 subunits of glutamate AMPA receptors in the central amygdala in modulating behavioral response to pain and opioid withdrawal. The findings reveal that the protein level of GluA1 in the central nucleus of the amygdala was significantly increased in rats under persistent pain and viral upregulation of GluA1 increased pain responses. However, the viral upregulation of GluA1 inhibited the aversion induced by naloxone-precipitated morphine withdrawal, while knockdown of GluA1 enhanced it. This suggests a differential action of GluA1 on the aversive event of sensory pain and opioid withdrawal.


UBERON:0002883


PUBCHEM.COMPOUND:5284596


UMLS:C0262593

The study found that Toll-like receptor 7 (TLR7), a protein found in neurons of the dorsal root ganglion (DRG), contributes to neuropathic pain. Peripheral nerve injury led to an increase in TLR7 expression in mice. Blocking this increase alleviated pain hypersensitivities. Conversely, artificially increasing TLR7 led to increased pain responses. The study suggests that TLR7 activates the NF-κB signaling pathway in primary sensory neurons, contributing to neuropathic pain. Therefore, TLR7 could be a potential target for therapeutic treatment of neuropathic pain.


PR:000001158


PR:000001158

potential target for therapeutic treatment of


UMLS:C5447544

GRM2-tdtomato anterior cingulate cortex neurons

Group II metabotropic glutamate receptor subtype 2

The study investigates the role of group II metabotropic glutamate receptor subtype 2 (GRM2) in the anterior cingulate cortex (ACC), a region associated with emotional processing of pain. Using a mouse model, the researchers found that a population of pyramidal neurons in the ACC, which express GRM2, become hyperexcitable under conditions of inflammatory and neuropathic pain. This hyperexcitability was reversed by the application of a GRM2 agonist, suggesting that these neurons and their associated receptors undergo changes in response to pain and could potentially be targeted for pain relief.


UMLS:C5447544


UMLS:C0856984


UMLS:C0039038

The study investigates the effect of local sympathectomy, a procedure that involves cutting the sympathetic nerves, on chemotherapy-induced neuropathic pain in mice. The mice were given the chemotherapeutic drug paclitaxel, which often causes neuropathic pain in cancer patients. The results showed that local sympathectomy led to a quick recovery from mechanical allodynia (pain response to non-painful stimuli) and prevented the development of cold allodynia. This was associated with an increase in anti-inflammatory responses, specifically the upregulation of macrophage markers and the anti-inflammatory cytokine, transforming growth factor-β (TGF-β). Blocking TGF-β signaling or depleting monocytes/macrophages reversed the pain relief provided by sympathectomy. Furthermore, administering TGF-β was sufficient to relieve mechanical allodynia, suggesting that local sympathetic nerves control immune responses and pain-like behaviors in mice after paclitaxel treatment.


UMLS:C0039038


UMLS:C0459521


UMLS:C0002915

The study suggests that general anesthesia (GA) can suppress pain by activating a specific group of neurons in the central amygdala (CeAGA neurons) of mice. These neurons are activated by different GA drugs and their activity is more related to the internal state of the animal than external stimuli. When these neurons are activated, they suppress pain and when inhibited, they exacerbate pain. The study suggests that these neurons could be a potential therapeutic target for chronic pain relief.


UMLS:C0815002


UMLS:C3494301

Neuropathic pain-induced mechanical (hyper-)sensitivity


UMLS:C3894754


CL:4023012

potential therapeutic target for alleviating


UMLS:C5551447

The study investigates the effect of sex on motor function, lesion size, and neuropathic pain after a contusion spinal cord injury in male and female C57BL/6 mice. The results showed that motor function was largely similar between sexes, but all males and only half of the females recovered plantar stepping. Females had a shorter rostral-caudal lesion length than males. All animals, regardless of sex, developed mechanical allodynia and heat hyperalgesia after the injury. There were no significant differences in pain outcomes between sexes.


NCBIGene:4280


NCBIGene:4280

The study used next-generation transcriptomics and imaging-based approaches to compare the expression of population markers in mouse and human dorsal root ganglion (DRG) neuronal subpopulations. The study found a large overlapping CGRP and P2X3R neuronal subpopulation in human lumbar DRG that was not present in mouse. There was also differential expression in a variety of mRNAs for transient receptor potential channels, cholinergic receptors, potassium channels, sodium channels, and other markers/targets. These findings suggest that sensory system organizational principles are likely different between both species.


UMLS:C3253774


NCBIGene:13494


UMLS:C1511448


NCBIGene:13494

mRNAs for transient receptor potential channels, cholinergic receptors, potassium channels, sodium channels


UMLS:C0039038

The study found that a localized sympathectomy, a procedure that involves cutting certain nerves, reduced pain behaviors and peripheral nerve regeneration in two rat models of neuropathic pain. This procedure also reduced the expression of growth-associated protein 43 (GAP43), a protein related to nerve regeneration, and the density of macrophages, immune cells that can affect nerve function. These findings suggest that while sympathetic blockade can relieve pain, it may also inhibit beneficial nerve regeneration.


NCBIGene:36727

The paper discusses the role of cyclin-dependent kinase 5 (Cdk5) in neuropathic pain. Cdk5 and its activators p35 and p39 are expressed in spinal nerves, dorsal root ganglia, and the dorsal horn of the spinal cord. In conditions of neuropathic pain, the expression or activity of Cdk5 is increased. The paper suggests that Cdk5 is regulated through its own phosphorylation, through increasing p35's interaction with Cdk5, and through cleavage of p35 into p25. The paper also discusses the molecular mechanisms of Cdk5-mediated regulation of target proteins involved in neuropathic pain, including channels, proteins involved in neurotransmitter release, and receptors. The paper concludes that Cdk5 could be a potential target for treating neuropathic pain conditions.


UMLS:C0662945


UMLS:C0384842

The study investigates the role of spinal neuropeptide Y (NPY) in inhibiting chronic pain and itch. The research focuses on the Gi-coupled neuropeptide Y1 receptor (Y1), which is found in areas of pain transmission. The study found that selective removal of spinal Y1-interneurons reduces the development of hypersensitivity caused by peripheral nerve injury. On the other hand, reducing NPY expression or administering Y1 antagonists reinstates hypersensitivity in models of chronic latent pain sensitization. The study suggests that spinal NPY release and the subsequent inhibition of pain facilitatory Y1-interneurons is a significant mechanism of endogenous analgesia. This mechanism can be replicated with pharmacological approaches to inhibit hypersensitivity and spinal neuron activity in rodent models of neuropathic, inflammatory, and postoperative pain. Activation of Y1 also inhibits itch. The study concludes that Y1-interneurons could be a promising therapeutic target for treating chronic pain and itch.


UMLS:C4075888

Selective ablation of spinal Y1-interneurons

Peripheral nerve injury-induced hypersensitivity


UMLS:C1266800


UMLS:C1511372

The study reveals that adult K/BxN transgenic mice, both males and females, develop spontaneous autoimmune arthritis with joint remodeling and significant bone loss. This condition is accompanied by severe sustained tactile allodynia, which is reduced by gabapentin but not by ketorolac. The study also found increased GFAP+ astrocytic cells in the dorsal horn in both genders, but an increase in Iba1+ microglia was observed only in males. In the dorsal root ganglia (DRG), there was an increase in CGRP+, TH+, and Iba1+ (macrophage) labeling, but no increase in ATF3+ cells. At the ankle, there was increased CGRP+, TH+, and GAP-43+ fiber synovial innervation. These findings suggest that adult K/BxN transgenic arthritic mice display a neuropathic phenotype, which is consistent with the analgesic pharmacology seen in this animal model.


UMLS:C0751213


UBERON:0002256


UMLS:C1511372


MONDO:0024317


PR:000009780

The study reveals that legumain (Lgmn), a cysteine protease, is activated in oral squamous cell carcinoma (OSCC), one of the most painful cancers. Lgmn cleaves protease-activated receptor-2 (PAR2) in the acidic OSCC microenvironment, causing pain. The study found that Lgmn evoked pain in female mice but not in mice lacking PAR2 or treated with a Lgmn inhibitor. The study also found that Lgmn activated PAR2 to induce calcium mobilization, cAMP formation, and activation of protein kinase D (PKD) and protein kinase A (PKA), but not β-arrestin recruitment or PAR2 endocytosis.


PR:000009780


CL:0002470

The study investigates the role of CCR2-expressing macrophages in a mouse model of low back pain and radiculopathy. It was found that local inflammation of the dorsal root ganglia (DRG) induced pain behaviors in mice, which were dominated by increases in CCR2+ macrophages. The study also found that the primary endogenous ligand for CCR2, CCL2, was upregulated in inflamed DRG. Experimental manipulations that reduced the CCR2+ macrophage influx also reduced pain behaviors. These findings suggest a key role for the CCR2/CCL2 system in establishing the pain state in this model of inflammatory low back pain and radiculopathy.


CL:0002470


NCBIGene:729230


NCBIGene:6347


UMLS:C3827110


UMLS:C0935779


MONDO:0024317

The paper reviews the neuroimmunology of chronic pain, which includes conditions like low back pain, arthritis, persistent post-surgical pain, fibromyalgia, and neuropathic pain disorders. It emphasizes that most treatments focus only on neurons, even though signaling between immune cells, glia, and neurons is crucial for the onset and continuation of chronic pain. The paper discusses recent progress in understanding neuroimmune signaling mechanisms and potential therapeutic targets in rodent models of chronic pain. It also talks about new technologies to study, diagnose, and quantify neuroimmune contributions to chronic pain in patients.


UMLS:C0027842


UMLS:C1521840


UMLS:C1657933

Neuroimmune contributions to chronic pain


UMLS:C0655643

The study suggests that complex regional pain syndrome (CRPS) is a posttraumatic autoimmune disease. The research found that early CRPS patient IgM antibodies have pronociceptive effects in the skin and spinal cord of muMT fracture mice. The study also found that the pronociceptive effects of these antibodies were blocked by a C5a receptor antagonist or a global cytokine inhibitor. The study postulates that CRPS IgM antibodies bind to neoantigens in the fracture limb skin and corresponding spinal cord to activate C5a complement signaling in macrophages and microglia, evoking proinflammatory cytokine expression contributing to nociceptive sensitization in the injured limb.


MESH:C559761

C5a receptor antagonist (PMX53) or global cytokine inhibitor (pentoxifylline)

pronociceptive effects of CRPS IgM antibodies


UMLS:C0655643

C5a complement signaling in macrophages and microglia


UMLS:C0682972

The paper discusses the role of G protein-coupled receptors (GPCRs) in chronic pain, particularly in the digestive system. It explains how mediators from injured tissues activate GPCRs, leading to acute hyperexcitability and nociception. The paper also discusses the potential of endosomally targeted GPCR antagonists, biased agonists, and allosteric modulators in providing superior pain relief. The paper suggests that a deeper understanding of GPCR structure and function could lead to better treatments for gastrointestinal pain.


UMLS:C0243042


UMLS:C3850135

Biased agonists of µ-opioid receptors (MOPrs)


CHEBI:48406


PR:000030035


UMLS:C1257975

Chemotherapy-induced peripheral neuropathy (CIPN)

The study found that nasal administration of mesenchymal stem cells (MSC) can completely reverse the signs of chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of cancer treatment, in mice. This reversal is associated with the normalization of mitochondrial bioenergetics in DRG neurons and is dependent on IL-10 production. MSC from IL-10 knockout animals were not capable of reversing CIPN symptoms, and neither were WT MSC in mice lacking IL-10 receptors on peripheral sensory neurons. The researchers suggest that nasal MSC treatment could be a potential treatment for patients suffering from neurotoxicities of cancer treatment.


CHEBI:81550


UMLS:C1257975


NCBIGene:3586


MONDO:0700057

The paper discusses neuropathic pain, a common clinical disorder that significantly impacts the quality of life of patients. Opioids are often used to treat this disorder, but their effectiveness is limited due to the downregulation of opioid receptors in primary afferent neurons following peripheral nerve trauma. The paper explores the molecular mechanisms behind this downregulation, including alterations in epigenetic modifications, transcription factors, post-transcriptional modifications, and protein translation initiation in the neurons of the dorsal root ganglion (DRG). The paper suggests that understanding these mechanisms could provide new avenues for the prevention and treatment of neuropathic pain.


UMLS:C0262593


GO:2000475

contributes to induction and maintenance of


CL:0000084

The paper discusses the role of T cells, a part of the immune system, in suppressing pain. It suggests that the immune system actively contributes to the resolution of pain, which could explain why immunosuppressive drugs often fail to control pain. The paper also suggests that a dysregulation in certain immune functions could lead to chronic pain. Therefore, stimulating the immune system's natural pain resolution pathways could be a potential treatment for chronic pain.


UBERON:0002405


MESH:D007166


UMLS:C2371094


UMLS:C0312550


PR:000006680

The study investigates the role of non-SUMOylated CRMP2 in the regulation of voltage-gated sodium channel NaV1.7, which is crucial for neuronal excitability and pain signaling. The research found that when CRMP2 is not SUMOylated, it forms a complex with proteins Numb, Eps15, and Nedd4-2 to promote the endocytosis of NaV1.7. In mice with a specific mutation (CRMP2K374A/K374A) that prevents CRMP2 SUMOylation, there was a reduction in NaV1.7 membrane localization and currents in sensory neurons. This was also associated with a reversal of mechanical allodynia, a type of neuropathic pain. However, inhibiting clathrin assembly in nerve-injured male mice with the same mutation led to the development of persistent pain. The study concludes that the endocytic complex composed of Numb, Nedd4-2, and Eps15 is necessary for non-SUMOylated CRMP2-mediated internalization of sodium channels.


PR:000006680


PR:000037550


UMLS:C1157990


GO:0048268


NCBIGene:80036

The study investigates the role of Transient receptor potential melastatin 3 (TRPM3), a heat-activated ion channel, in various pain modalities. The research used two inhibitors of TRPM3, isosakuranetin and primidone, in mice with nerve injury-induced neuropathic pain. The results showed that these inhibitors reduced heat hypersensitivity in wild-type mice but not in TRPM3-/- mice. The study also found that TRPM3 plays a role in heat hypersensitivity and spontaneous pain after nerve injury, but not in cold and mechanical hypersensitivity.


NCBIGene:80036


PUBCHEM.COMPOUND:5280804


PUBCHEM.COMPOUND:4909


UMLS:C1563722

The paper discusses the role of Transient Receptor Potential (TRP) ion channels in orofacial pain, which includes conditions like temporomandibular joint disorders pain, trigeminal neuralgia, dental pain, and headaches. The research indicates that TRP ion channels, specifically TRPV1, TRPA1, TRPV4, and TRPM8, are expressed in the trigeminal sensory system and play a significant role in the transduction and pathogenesis of orofacial pain. The paper also highlights the unique characteristics of the orofacial sensory system compared to the spinal sensory system.


NCBIGene:7442


UBERON:0007641

involved in the transduction and pathogenesis of


UMLS:C0038369

shows distinct pain processing and different sensitivities from


UMLS:C0109529

The study investigates the effects of a neurokinin 1 receptor (NK1R) antagonist, Spantide I (Span), when conjugated to cholestanol (Span-Chol). The research found that Span-Chol accumulates in endosomes, inhibits endosomal NK1R signaling, and causes prolonged antinociception. Over time, Span-Chol increased local concentration at the plasma membrane, showed an increase in NK1R-binding affinity, and more potent inhibition of NK1R-mediated calcium signaling. Span-Chol also caused a persistent decrease in NK1R recruitment of β-arrestin and receptor internalization to early endosomes. In a preclinical model of pain, Span-Chol caused prolonged antinociception (>9 h), which is attributable to a three-pronged mechanism of action: increased local concentration at membranes, a prolonged decrease in NK1R endocytosis, and persistent inhibition of signaling from endosomes.


UMLS:C0109529


PR:000001393

The study investigates the role of Interleukin 6 (IL-6) in the development of adaptive immune responses and nociceptive sensitization in a mouse model of complex regional pain syndrome (CRPS). The findings suggest that IL-6 signaling is necessary for the development of nociceptive sensitization, vascular changes, and IgM immune complex deposition in the skin of injured limbs post-fracture. The study also found that the administration of anti-IL-6 antibodies reduced nociceptive and vascular changes after fracture and inhibited lymphadenopathy. Therefore, anti-IL-6 therapies might reduce pain after limb fracture or in the setting of CRPS.


PR:000001393


UMLS:C4086508


UMLS:C0600322

The study reviews the mechanisms and pathways through which light modulates pain. It shows that the application of red light (660 nm) on the skin can reduce pain in neuropathies and complex regional pain syndrome-I, while visual exposure to the same wavelength can worsen migraines and cause functional pain in animal models. However, visual exposure to green light can reduce pain in conditions like migraines and fibromyalgia. Both cutaneous and visual exposure cause changes in the brainstem, spinal cord, dorsal root ganglia, and nociceptors.


UMLS:C0600322


UMLS:C4316930


UMLS:C0031765


UMLS:C0301835

The study found that intermittent parathyroid hormone (iPTH) can reduce osteoarthritis pain in mice. This is achieved by inhibiting subchondral sensory innervation, subchondral bone deterioration, and articular cartilage degeneration. The iPTH treatment also reduced the level of prostaglandin E2 in the subchondral bone and regulated uncoupled subchondral bone remodeling. The study suggests that iPTH could be a potential disease-modifying therapy for osteoarthritis.


UMLS:C1295402


UMLS:C3658265

The study investigates the use of targeted epigenetic repression of NaV1.7, a sodium channel protein associated with pain signaling, as a potential treatment for chronic pain. The researchers used CRISPR-dCas9 and zinc finger proteins to repress NaV1.7 in primary afferents at the spinal level. The repression was delivered via adeno-associated viruses (AAVs) in three mouse models of pain. The results showed effective repression of NaV1.7, reduced thermal hyperalgesia in the inflammatory state, decreased tactile allodynia in the neuropathic state, and no changes in normal motor function in mice. This suggests that this method, dubbed pain LATER, could have therapeutic potential in the management of persistent pain states.


NCBIGene:9607

The cocaine- and amphetamine-regulated transcript peptide (CART) has been recognized since 1981, but its gene was only identified in 1995. The peptide has been linked to ingestive behaviors, reward behaviors, and pain sensation. Despite its potential, the lack of an identified receptor has limited its therapeutic development. However, the recent identification of GPR160 as a receptor for CART could lead to new pharmacotherapies.


NCBIGene:9607


CL:0000235

The study reveals that macrophages (MΦ) residing in the sciatic nerve contribute to cancer-induced pain in mice. The pain is mediated by an increase in MΦ-colony stimulating factor (M-CSF), which leads to the expansion of these macrophages, activation of the transient receptor potential ankyrin 1 (TRPA1), and oxidative stress. The TRPA1 in Schwann cells plays a crucial role in this process. Depleting these macrophages in the sciatic nerve reduces pain-like behaviors. The findings suggest a pathway involving M-CSF, macrophages, oxidative stress, and Schwann cell TRPA1 that signals cancer-induced pain.


PR:000000699


CL:0000235


MESH:C062290

Summary not provided or could not be parsed.


MESH:C062290


MESH:C062290

constipation, respiratory depression, hyperactivity


MESH:C062290

cAMP formation, β-arrestins recruitment, MOPr endocytosis


NCBIGene:19

The study found that neuroinflammation, a major component in neuropathic pain states, involves the activation of TLR4 in cholesterol-enriched lipid rafts, termed as inflammarafts. The deletion of cholesterol transporters ABCA1 and ABCG1 in microglia led to the formation of inflammarafts and induced tactile allodynia. The apoA-I binding protein (AIBP) was found to deplete cholesterol from inflammarafts and reverse neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN). However, AIBP failed to reverse allodynia in mice with ABCA1/ABCG1-deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia or reverse CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia.


PR:000004141


UMLS:C5432325


NCBIGene:9607

Cocaine- and amphetamine-regulated transcript

The paper discusses the diverse pharmacologic actions of the peptide, CARTp, encoded by the cocaine- and amphetamine-regulated transcript. The peptide has effects on the central and peripheral nervous systems and several endocrine organs, including the pancreas. The identification of a CARTp receptor, GPR160, has revealed the physiological importance and therapeutic potential of CARTp. The interaction between CARTp and GPR160 is essential for the circadian regulation of appetite and thirst and for the transmission of nerve injury-induced pain. Further research is being conducted to uncover more physiologically relevant actions of this ligand/receptor pair.


GO:0071906


MESH:D002116

The paper discusses the potential of the calcitonin family of peptides, which includes calcitonin, amylin, adrenomedullin, and adrenomedullin 2, as targets for migraine and pain treatment. These peptides show pro-nociceptive and anti-nociceptive actions in primary headache conditions like migraine. They are also expressed at sites relevant to migraine and pain, suggesting their potential therapeutic use in treating these conditions.


MESH:D002116

Pro-nociceptive and anti-nociceptive actions


UMLS:C0054487

The study found that painful diabetic neuropathy (PDN), a complication affecting 25% of diabetic patients, is characterized by neuropathic pain and dorsal root ganglion (DRG) nociceptor hyperexcitability, leading to calcium overload, axonal degeneration, and loss of cutaneous innervation. The researchers discovered that mitochondrial fission proteins were elevated in DRG neurons from mice with PDN induced by a high-fat diet (HFD). They also found that preventing calcium entry into the mitochondria by deleting the mitochondrial calcium uniporter restored normal mitochondrial morphology, prevented axonal degeneration, and reversed mechanical allodynia in the HFD mouse model of PDN. This suggests that targeting calcium entry into nociceptor mitochondria could be a promising therapeutic approach for PDN.


CL:1001451


NCBIGene:4280

The study investigates the pharmacology of the calcitonin (CT) receptor family in mice, which includes two receptors (the CT receptor [CTR] and the CTR-like receptor [CLR]), three accessory proteins (RAMPs), and multiple endogenous peptides. The study reports the first synthesis and characterisation of mouse adrenomedullin, adrenomedullin 2 and βCGRP and of mouse CTR without or with mouse RAMPs. The pharmacological profiles of receptors comprising m-CLR:m-RAMPs were generally similar to those of their human counterparts, albeit with reduced specificity. The study concludes that mouse receptor pharmacology differs from that in humans, with mouse receptors displaying reduced discrimination between ligands.


NCBIGene:11535


NCIT:C123624


UMLS:C5391524


PR:000001068

Transient Receptor Potential Vanilloid 4 (TRPV4)


UMLS:C3813211

The study found that the concentration of prostaglandin E2 (PGE2) increases in porous vertebral endplates, leading to spinal pain. High-dose treatment with celecoxib, a cyclooxygenase 2 inhibitor, reduced PGE2 concentration and spinal pain, but also impaired bone formation and the pain returned after discontinuing the treatment. However, low-dose celecoxib treatment resulted in a sustained reduction in spinal pain even after discontinuing the treatment. This was associated with a significant reduction in endplate porosity, decreased sensory nerve innervation, and maintained PGE2 concentration at the physiological level.


UMLS:C5560161


UMLS:C1337049

The study identifies genes that are exclusively expressed in different types of neurons in mice. It was found that the pituitary hormone genes prolactin (Prl), growth hormone (Gh), and proopiomelanocortin (Pomc) are almost exclusively expressed in trigeminal (TG) neurons. The study also found that growth hormone (GH) plays a significant role in pain responses in the trigeminal system, causing mechanical hypersensitivity when injected into the masseter muscle and dura. This hypersensitivity was reversed by a GH receptor antagonist, pegvisomant.


UNII:N824AOU5XV


UMLS:C0064239

The study investigates the sex differences in pain sensitization after surgery, which is controlled by kappa opioid receptors in the spinal cord. The research found that a pronociceptive latent pain sensitization persists for over a year after surgical incision and is regulated by the analgesic activity of kappa opioid receptors. The signaling pathways NMDAR→AC1→cAMP→Epac in the dorsal horn of the spinal cord maintain this sensitization in both males and females. However, only males recruit a PKA-dependent mechanism. This suggests a novel male-specific mechanism for the promotion of chronic postoperative pain.


UMLS:C2267184


UMLS:C0086582


UMLS:C0184898

pronociceptive latent pain sensitization


NCBIGene:1520

The study reveals that Cathepsin S, a lysosomal cysteine protease, is more active in oral squamous cell carcinoma (SCC) than in normal tissue. It is generated by carcinoma and macrophages in the oral cancer microenvironment. Cathepsin S activates protease-activated receptor-2 (PAR2), contributing to cancer pain. The pain was significantly reduced in mice lacking PAR2 in Nav1.8-positive neurons or treated with an endogenous cathepsin S inhibitor. The human oral SCC cell line with a homozygous deletion of the gene for cathepsin S also provoked less pain.


NCBIGene:1520


PR:000008817

Mechanical allodynia and thermal hyperalgesia


UMLS:C0014139

The study identifies nociceptor endocytosis as a potential target for local, specific, and long-lasting treatment of inflammatory pain. The research found that AP2α2, an α-subunit isoform of the AP2 complex, is preferentially expressed within CGRP+/IB4- nociceptors in rodents and in CGRP+ dorsal root ganglion neurons from a human donor. Inhibiting nociceptor endocytosis through genetic and pharmacological approaches demonstrated its role in the development and maintenance of acute and chronic inflammatory pain. A one-time injection of an AP2 inhibitor peptide significantly reduced acute and chronic pain-like behaviors and provided prolonged analgesia. The study also found sexually dimorphic recovery responses to this pharmacological approach, emphasizing the importance of sex differences in pain development and response to analgesics.


PR:000004100


MESH:C509263


UMLS:C2219909


UBERON:0002410

The study investigates the role of the autonomic nervous system in regulating the activation of the adaptive immune system and nociceptive sensitization in a mouse model of chronic post-traumatic pain with features of complex regional pain syndrome (CRPS). The findings suggest that inhibiting sympathetic signaling or augmenting parasympathetic signaling can reduce nociceptive sensitization and immune system activation, which are associated with limb fracture. This could potentially alleviate persistent post-traumatic pain and CRPS.


UMLS:C2267069


UMLS:C2267067


UMLS:C0004112

The study reveals a new function of astrocytes in the spinal cord, contributing to the gating of pain signals. The research found that electrical stimulation of peripheral Aβ-fibers in mice activated spinal astrocytes, which then induced long-term depression in NK1R+ neurons and antinociception through activation of endogenous adenosinergic mechanisms. The suppression of astrocyte activation blocked the induction of long-term depression in NK1R+ neurons and pain inhibition by Aβ-fiber stimulation. This suggests that astrocytes play a significant role in nonneuronal control of pain.


UMLS:C0475316


UMLS:C0004112

Long-term depression (LTD) in NK1R+ neurons


GO:0002265


UMLS:C1997216

The study investigates the mechanisms of spontaneous pain, which is pain that occurs without external stimuli and is a common symptom in chronic pain conditions. The researchers discovered a unique form of abnormal spontaneous activity in dorsal root ganglion (DRG) neurons after peripheral nerve injury: clusters of adjacent DRG neurons firing synchronously and sporadically. This cluster firing is triggered by the activity of sympathetic nerves, which grow into DRGs after injury, and norepinephrine was identified as the key neurotransmitter mediating this firing. The level of cluster firing directly correlated with nerve injury-induced spontaneous pain behaviors. Manipulations of sympathetic activity and norepinephrine receptors suggest they are necessary for DRG cluster firing and spontaneous pain behavior. Therefore, blocking this cluster firing may be a new approach to treating spontaneous pain.


CL:1001451


UMLS:C0459521


PUBCHEM.COMPOUND:439260


GO:0098874


UMLS:C0068979

Sympathetic activity and Norepinephrine receptors

Cluster firing and Spontaneous pain behavior


UBERON:0002405

The study reveals that the immune system plays a dual role in pain regulation. It can both enhance pain through proinflammatory mediators produced by T cells and macrophages, and promote pain resolution through anti-inflammatory mediators and endogenous opioids.


CL:0000235


UMLS:C1563722

Transient receptor potential (TRP) ion channels

involved in the generation and progression of

The study discusses the role of transient receptor potential (TRP) ion channels in the generation and progression of chronic pain. Despite being targeted by pharmaceutical companies for pain relief, TRP channel inhibitors have failed in clinical trials due to their thermoregulatory function. The study also highlights the emerging role of Botulinum neurotoxins (BoNTs) as potential pain therapeutics due to their regulation of exocytosis and pro-nociceptive neurotransmitters. The study suggests that BoNTs may also regulate the expression and function of TRP channels, which could explain their analgesic effects.


UNII:E211KPY694

Exocytosis and pro-nociceptive neurotransmitters


UNII:E211KPY694

Transient receptor potential (TRP) ion channels

may regulate the expression and function of


NCBIGene:7223

The study investigates the role of transient receptor potential cation channel subfamily C member 4 (TRPC4) in pain and its potential as a target for migraine treatment. The researchers found that TRPC4 is highly expressed in trigeminal ganglia and its activation mediates both itch and pain. The small-molecule inhibitor ML204, a specific TRPC4 antagonist, significantly reduced migraine-like behaviors in mice. Additionally, ML204 treatment resulted in a significant decrease in CGRP protein levels in the plasma, which largely prevented the development of chronic migraine-like behavior. These findings suggest that TRPC4 could be a potential target for migraine treatment.


MESH:C000611564


NCBIGene:7223


CHEBI:35482

The paper discusses the potential of nanotechnology in pain management. Current pain treatments, which primarily rely on opioid analgesics, are unsatisfactory due to their life-threatening side effects and addictive properties. Nanomedicine could provide a solution to these challenges by offering targeted treatments without the associated burdens of current clinical pain therapies. The paper highlights advances in nanoparticle-based drug delivery, gene therapy, and nanomaterials-based scavenging as potential methods for effective pain treatment.


UMLS:C0391976


UMLS:C5205585


CHEBI:61115

The study investigates the role of Histone deacetylase 6 (HDAC6) inhibitors in reversing chemotherapy-induced peripheral neuropathy (CIPN), a condition affecting many cancer survivors. The research found that HDAC6 inhibitors can reverse CIPN by increasing macrophage-derived IL-10 signaling to IL-10 receptors on Advillin+ sensory neurons. This process helps resolve mechanical hypersensitivity, a symptom of CIPN. Additionally, HDAC6 inhibitors can restore axonal mitochondrial health, which is often compromised by cisplatin, a chemotherapy drug. These findings suggest that HDAC6 inhibitors could be a potential treatment for CIPN.


CHEBI:61115

increases signaling to IL-10 receptors on Advillin+ sensory neurons


CHEBI:61115


CHEBI:81550


PR:000002102

The research paper discusses the role of the sodium channel isoform NaV1.7 in transmitting pain information. The study reveals that direct targeting of this channel has been unsuccessful, but an indirect approach, disrupting interactions with accessory protein partners, has shown promise. The researchers have found that a small-molecule inhibitor of CRMP2 SUMOylation, compound 194, selectively reduces NaV1.7 currents in DRG neurons. This compound has also shown to reverse mechanical allodynia in a chronic constriction injury (CCI) model of neuropathic pain. The study concludes that compound 194 is a robust inhibitor of NaV1.7 function and can significantly alleviate mechanical allodynia associated with nerve injury.


MESH:C016897


PR:000006680

Spontaneous excitatory postsynaptic currents

The study investigates the role of collapsin response mediator protein 2 (CRMP2) in the initiation and maintenance of chronic pain. The researchers found that the knockdown of CRMP2 in the spinal cord of rats reduced the frequency and amplitude of spontaneous excitatory postsynaptic currents, which are involved in pain signaling. However, this effect was not observed in astrocytes. The conditional knockout of CRMP2 in neurons also reversed established mechanical allodynia (a type of pain) induced by a spared nerve injury in mice. These findings suggest that CRMP2 is a key regulator of glutamatergic neurotransmission driving pain signaling and contributes to the transition of physiological pain into pathological pain.


PR:000006680


UMLS:C0993583

The study investigates the analgesic mechanism of contulakin-G (CGX), a conotoxin peptide and neurotensin analogue. The research suggests that CGX produces antinociception (pain relief) through the activation of the presynaptic neurotensin receptor (NTSR)2. This effect was observed to be dose-dependent and was reversed by pharmacological and gene editing of NTSR2. The study also found that CGX inhibition was dependent on the R-type voltage-gated calcium channel (Cav2.3) in sensory neurons. The findings reveal a nonopioid pathway for pain relief.


UMLS:C0993583


UMLS:C0993583

R-type voltage-gated calcium channel (Cav2.3)


PR:000001628


NCBIGene:4280

The study investigates the trafficking and signaling of protease-activated receptor 2 (PAR2) in colitis. Researchers generated knockin mice expressing PAR2 fused to monomeric ultrastable green fluorescent protein (muGFP). The study found that in healthy mice, PAR2-muGFP was prominently localized to the basolateral membrane of colonocytes. However, in mice with colitis, PAR2-muGFP was depleted from the plasma membrane of colonocytes and redistributed to early endosomes. This is consistent with the generation of proinflammatory proteases that activate PAR2. The study suggests that PAR2 endocytosis sustains protease-evoked inflammation and nociception and that PAR2 in endosomes is a potential therapeutic target for colitis.


UMLS:C0293065


GO:0002499


UMLS:C0259628


UMLS:C0006669

The study reveals that the calcitonin gene-related peptide (CGRP) released from mouse cutaneous trigeminal fibers targets CLR/RAMP1 on surrounding Schwann cells to evoke periorbital mechanical allodynia. The activation of CLR/RAMP1 in human and mouse Schwann cells generates long-lasting signals from endosomes that evoke cAMP-dependent formation of NO. This NO, by gating Schwann cell transient receptor potential ankyrin 1 (TRPA1), releases ROS, which in a feed-forward manner sustain allodynia via nociceptor TRPA1. The study suggests that the CGRP-mediated neuronal/Schwann cell pathway mediates allodynia associated with neurogenic inflammation, contributing to the algesic action of CGRP in mice.


GO:0002271


CHEBI:25585


UMLS:C0456922

CGRP-mediated neuronal/Schwann cell pathway


UMLS:C0242402

The study found that chronic high-dose opioid exposure leads to opioid tolerance and features of opioid-induced hyperalgesia in the colon. This action is mediated by Delta-Opioid Receptor (DOPr) signaling and is dependent on receptor endocytosis and downstream protein kinase C signaling. The role of DOPr was found to be central in the development of opioid tolerance and opioid-induced hyperalgesia in colonic afferent nociceptors following prolonged exposure to high concentrations of MOPr or DOPr agonists.


UMLS:C0242402


PR:000001579


PR:000045382


UMLS:C0242629

The study found that the resolution of chemotherapy-induced peripheral neuropathy (CIPN), a type of chronic pain, depends on CD8+ T cells and IL-10 produced by other cells. The research showed that CD8+ T cells producing IL-13 were required for resolution of CIPN. The study also found that cell damage induced by cisplatin activated TIM3 on CD8+ T cells, leading to increased IL-13 production, which in turn induced macrophage IL-10 production and resolution of CIPN. This suggests that developing activators of the IL-13/IL-10 pain resolution pathway could potentially treat the underlying cause of chronic pain.


PR:000001370


CHEBI:81550


UMLS:C5237935


NCBIGene:5020

The study investigates the role of Oxytocin (OT) in pain-related disorders, specifically in the comorbidity of temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS). The research used a rat model with masseter muscle inflammation combined with stress, which mimics the comorbidity of TMD and FMS. The study found that spinal administration of OT reduced hyperalgesia (increased sensitivity to pain) in the hindpaws of the rats. This effect was blocked by the administration of OT receptor antagonist atosiban or 5-HT2A receptor antagonist ritanserin, suggesting that OT's analgesic effect is mediated through these receptors. This suggests a potential therapeutic role for OT in treating patients with TMD and FMS.


UMLS:C0069841


UMLS:C0289174


UMLS:C0873206


UMLS:C2698070


UBERON:0001954

Chronic multisite musculoskeletal pain (CMP)

The study investigates the vulnerability factors for chronic multisite musculoskeletal pain (CMP). It was found that small hippocampal brain volume and FKBP5 genetic risk, along with severity of childhood trauma, increase vulnerability for CMP. The interaction between FKBP5 genetic risk and right hippocampal volume was associated with CMP severity. The study used data from 36,822 individuals from the UK Biobank study.


NCBIGene:14229


UMLS:C5544356


UMLS:C0439656

The study found that voluntary wheel running before nerve injury can prevent chronic pain in both male and female rats. This is achieved by maintaining redox homeostasis after sciatic nerve injury. The study showed that 6 weeks of voluntary wheel running reduced neuropathic pain development induced by chronic constriction injury. This was associated with reduced nitrotyrosine immunoreactivity, a marker for peroxynitrite, at the sciatic nerve injury site. The study also found that voluntary wheel running increased superoxide scavenging by elevating the expression of superoxide dismutases 1 and 2. The prevention of neuropathic pain was associated with the activation of nuclear factor E2-related factor 2 (Nrf2), a master transcriptional regulator of the antioxidant response.