NCBIGene:100043582

The study investigates the functional differences between the two alleles of rs678849, a genetic variant in the delta-opioid receptor gene (OPRD1) associated with substance use disorder phenotypes, regional brain volume, addiction risk, and the efficacy of buprenorphine/naloxone in treating opioid use disorder. The research found that the C allele construct had significantly lower luciferase expression than the T allele construct. Proteomic analysis identified XRCC6 as a transcription factor specifically binding the C allele, whereas hnRNP D0 was found to specifically bind the T allele. These differences may explain the psychiatric and neurological phenotype differences predicted by rs678849 genotype.


NCBIGene:100043582


UMLS:C0427362


NCBIGene:2547


UMLS:C0377278


UMLS:C0242402

The study aims to identify clinical and genetic factors that increase the risk of developing opioid use disorder (OUD) in individuals using prescription opioids (POs) for pain relief. The researchers are conducting a prospective observational study using an existing biobank that includes whole exome sequencing and array genotyping. The data capture includes self-report surveys measuring addiction severity, depression, anxiety, and nicotine use, as well as clinical, prescription, and brain imaging data extracted from electronic health records.


UMLS:C0541756


UMLS:C2362914


UMLS:C0242402

Total hip and knee arthroplasty (THA and TKA)

The study investigates the reasons for preoperative opioid use in patients undergoing total hip and knee arthroplasty (THA and TKA). It was found that patients who used opioids for combined reasons (surgical site pain and pain in other body areas) had greater odds of persistent use at 3 and 6 months postoperatively. This suggests that nonsurgical pain, in part, drives persistent opioid use after surgery. The study emphasizes the need for tailored postoperative opioid weaning plans that consider both pain and non-pain reasons for presurgical opioid use.


UMLS:C0242402


UMLS:C3658215

The paper discusses the use of Pragmatic Clinical Trials (PCTs) to address the dual public health crises of chronic pain and opioid misuse, which have been exacerbated by the COVID-19 pandemic. The National Institutes of Health, Department of Defense, and Department of Veterans Affairs have formed an interagency research partnership, the Pain Management Collaboratory, to advance nonpharmacological approaches and integrated models of care for pain management and common co-occurring conditions. The partnership supports 11 large-scale, multisite PCTs in veteran and military health systems.


UMLS:C3658215


UMLS:C0027468


UMLS:C1511775


UMLS:C0041735


CHEBI:30879

associated with new persistent opioid use after

The study found that among patients not using opioids at the time of surgery, those with a history of opioid use were more likely to continue using opioids 3 months after surgery. This was particularly true for patients with a history of continuous opioid use. Moderate to high alcohol use was also associated with new persistent opioid use and opioid prescription refill 1 month after surgery.


UMLS:C1562611

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 in consumption was dose-dependent, with chronic users reporting the highest consumption. Among those receiving perioperative prescriptions, patients with prior opioid exposure had a higher likelihood of refill, number of refills, and average refill amount. The study suggests that existing guidelines may meet the postoperative needs of most patients with preoperative opioid exposure, but may need to be tailored for patients with chronic use.


UMLS:C0150706


UMLS:C0242402

The study found that new persistent opioid use after benign hysterectomy was associated with several factors. These include 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 the total morphine milligram equivalent of ≥300 in the first perioperative prescription and dispensing of a first perioperative prescription before the surgery increased the likelihood of persistent use. However, minimally invasive hysterectomy and a more recent surgery year significantly decreased its likelihood.


PUBCHEM.COMPOUND:5288826


MONDO:0002025


HP:0012531


UMLS:C0301389


UMLS:C0302836


UMLS:C0742723


UMLS:C1283820


UMLS:C4324621

The study investigates the cause of death among West Virginia Medicaid enrollees discharged from hospitalization due to infective endocarditis (IE), with a focus on those diagnosed with 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.


UMLS:C0261435


UMLS:C0032606

Mental and behavioral disorders due to polysubstance use


MONDO:0004995


UMLS:C0772354


UMLS:C5540804

increases the need for timely treatment in


UMLS:C0242402

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:C0242402

The study investigated the impact of prenatal opioid exposure on the global brain network connectivity in infants. Using resting-state functional MRI, the researchers found significant differences in the brain network connectivity of infants exposed to opioids prenatally compared to healthy control infants. Four network components were significantly different between the two groups, two of which were associated with maternal psychological factors. The study also found that prenatal opioid exposure was associated with alterations in intra-network graph metrics, including average flow coefficient, clustering coefficient, and transitivity. These network alterations were also associated with maternal comorbidity, particularly mental health.


UMLS:C0242402


UMLS:C1135956


CHEBI:35482

The study investigates how adolescents manage pain after third molar dental extractions, with a focus on the use of opioid and non-opioid analgesics. The study found that most adolescents and their parents discussed pain management plans that included non-medication options, over-the-counter medications, and opioid medications to be taken as needed. All participants reported receiving an opioid prescription for post-extraction pain management, but most only took it on the day of the extraction and up to 2 days following. The study suggests that providers may have an opportunity to reduce the number of opioids prescribed, and should educate patients and their parents about safe disposal of opioids to mitigate the potential for diversion.


UMLS:C0556027


UMLS:C0577760


UMLS:C2114037

Neonatal opioid withdrawal syndrome (NOWS)

The study investigates the impact of prenatal opioid exposure (POE) on neonatal opioid withdrawal syndrome (NOWS) severity. The researchers used resting-state functional magnetic resonance imaging (rs-fMRI) to assess alterations in thalamic functional connectivity in neonates with POE. The results showed significant alterations in thalamic to cortical functional connectivity in infants with POE compared to healthy infants. These alterations were found to correlate with the severity of NOWS. The study suggests that future research could use thalamocortical resting state functional connectivity to stratify the risk of long-term neurodevelopmental outcomes in infants with POE.


UMLS:C2114037


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 maximum period between prescription writing and dispensing. The data showed that in 2019, out of 20,858,413 opioid prescriptions, 194,452 (0.9%) had delayed dispensing. The study also found that a law enacted in Minnesota in July 2019, which precluded opioid prescription dispensing more than 30 days after writing, decreased delayed dispensing prevalence by 0.22 percentage points.


UMLS:C0242402

The study compared the reliability of Michigan's prescription drug monitoring program (PDMP) and a national pharmacy prescription database (Surescripts) in tracking opioid prescription fulfillment after surgery. The study found that the PDMP was more likely to capture fulfillment among younger and publicly insured participants, while Surescripts was more likely to capture fulfillment from counties bordering neighboring states. The PDMP detected 2 times more patients with persistent opioid use compared to Surescripts.


UMLS:C0699778

The study reveals a significant increase in infective endocarditis (IE) cases in West Virginia, primarily due to injection drug use. The study found that patients with drug use-associated IE (DU-IE) were younger, had longer hospital stays, and had a higher proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates, psychiatric disorders, cardiac surgeries, and discharges against medical advice compared to patients with non-DU-IE. Drug use was found to be an independent predictor of the combined outcome of discharge against medical advice/in-hospital mortality.


MONDO:0000565


UMLS:C3864091

The study examined the association and trajectory of perioperative anxiety, pain, and opioid use following common surgical procedures. It was found that anxiety and surgical site pain were highest on the day of surgery and declined in the follow-up period. Patients with anxiety reported higher opioid use and an increase in patient-reported surgical pain compared to those without anxiety. However, anxiety did not significantly mediate the relationship between pain and opioid use. The study concluded that anxiety is an independent risk factor for increased pain and opioid use after surgery.


UMLS:C3864091


UMLS:C1948041


UMLS:C3266208

The study aimed to develop a clinical tool to predict severe pain during dressing changes in patients with open skin wounds. The study identified three predictors that are most useful for a clinical prediction tool: type of dressing, resting wound pain, and expected pain. Algorithms based on these predictors can be used to predict patients likely to experience severe pain during a dressing change. This tool is important as it can help target patients for preventive pain control strategies.


UMLS:C0241745


UMLS:C0578072


UMLS:C0242402

The study examined 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 had this procedure filled an opioid prescription perioperatively. Of 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 opioids and skeletal muscle relaxants, opioids and benzodiazepines, and opioids with skeletal muscle relaxants and benzodiazepines were significantly more likely to refill opioid prescriptions. The study suggests that coprescribing of opioids with skeletal muscle relaxants may potentiate opioid use after surgery and should be avoided due to the risks of sedation.


UMLS:C3653964


PUBCHEM.COMPOUND:134664


UMLS:C3494272


UBERON:0035017

The study found that pain-sensing neurons, or nociceptors, play a role in regulating intestinal inflammation. In a mouse model of intestinal damage and inflammation, the silencing or removal of TRPV1+ nociceptors led to more severe inflammation and impaired tissue repair processes. This was associated with significant changes in the intestinal microbiota. The presence of Gram+Clostridium spp. in germ-free mice promoted intestinal tissue protection through a nociceptor-dependent pathway. The disruption of nociception resulted in decreased levels of substance P, a protein involved in pain perception. Therapeutic delivery of substance P promoted tissue-protective effects in a microbiota-dependent manner. Dysregulated nociceptor gene expression was also observed in intestinal biopsies from patients with inflammatory bowel diseases.


UBERON:0035017


UMLS:C0445965


HP:0007021


UMLS:C0075381


UMLS:C0314621


UMLS:C0005865

The study examined the impact of a payment incentive by Blue Cross Blue Shield of Michigan (BCBSM) for opioid-sparing vasectomies on the percentage of patients who filled opioid prescriptions before and after the procedure. The results showed a significant reduction in the percentage of men who filled opioid prescriptions after vasectomy following the implementation of the incentive. There was a 19.9% absolute reduction and 61.0% relative reduction in opioid prescription fills after the incentive was introduced. No significant change was observed in the control group.


UMLS:C0242402


UMLS:C0054377

The study investigates the in vivo efficacy of a novel small molecule/peptidomimetic hybrid compound, C781, as a β-arrestin-biased Protease-Activated Receptor-2 (PAR2) antagonist. 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 efficacious in the carrageenan inflammation model. The study suggests that optimizing pharmacokinetic properties could improve in vivo efficacy of C781.


UMLS:C0054377

prevents and reverses nociceptive behaviors induced by


UMLS:C0054377


UMLS:C5237389

The study discusses the treatment of Neonatal abstinence syndrome (NAS), a condition that infants develop after intrauterine maternal drug exposure. The Finnegan Score is used to monitor infants with opioid exposure, with a score of >8 suggesting exposure. Non-pharmacological approaches are the first line of treatment for all infants, regardless of initial symptoms. However, if symptoms persist despite supportive care, pharmacological treatment is recommended, which can be life-saving in severe cases.


UMLS:C1609039


UMLS:C0013216


UMLS:C0033052

Neonatal opioid withdrawal syndrome (NOWS)

The study examined the variation in care for infants with neonatal opioid withdrawal syndrome (NOWS) across different sites. The study found significant variation in maternal-infant characteristics, infant management, and outcomes for infants with NOWS across 30 participating hospitals. The variation included 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, receiving pharmacologic therapy, secondary medications, and nonpharmacologic interventions. The mean length of stay and the proportion of infants discharged with their parents also varied across sites. The study concluded that the observed variation makes it unlikely that all infants are receiving efficient and effective care for NOWS.


UMLS:C1290954


UMLS:C0850266


UMLS:C1278213


UMLS:C0520018


UMLS:C0016498


UMLS:C0885503


UMLS:C1256370

shortens hospital stay and duration of treatment

The study investigates the effectiveness of phenobarbital and clonidine as secondary medications for neonatal opioid withdrawal syndrome (NOWS) when first-line opioid medications fail. The study found that infants treated with phenobarbital had a shorter hospital stay and shorter duration of morphine treatment compared to those treated with clonidine. However, infants were more likely to be discharged from the hospital on phenobarbital than clonidine. The potential neurodevelopmental consequences of phenobarbital use in infants with NOWS need further investigation.


UMLS:C0949270

longer hospital stay and duration of treatment compared to Phenobarbital


UMLS:C1256370


UMLS:C0242402

Neonatal opioid withdrawal syndrome (NOWS) is a risk for newborns whose mothers consumed opioids during pregnancy. Nonpharmacologic treatment is usually the first line of management, with pharmacologic treatment added if necessary. Morphine and methadone are commonly used, but buprenorphine is emerging as a potential treatment option based on its pharmacologic profile and results from initial clinical trials. This report discusses the current state of knowledge and practical considerations regarding the use of buprenorphine for NOWS treatment.


PUBCHEM.COMPOUND:5288826


PUBCHEM.COMPOUND:643985


UMLS:C0701445


UMLS:C1541533

The study investigates the effects of the cannabinoid receptor type 1 (CB 1) agonist CB-13 on pain in mice. Acute dosing of CB-13 reduced inflammation-induced pain in a peripheral CB 1-receptor-dependent manner and relieved thermal hyperalgesia. This was achieved by reducing TRPV1 sensitization and neuronal hyperexcitability induced by the inflammatory mediator prostaglandin E 2. However, repeated dosing led to analgesic tolerance and CB 1 receptor dependence, suggesting increased central nervous system (CNS) exposure and unwanted engagement of central CB 1 receptors.


UMLS:C1541533


UMLS:C0242406

The study developed an automated pipeline using convolutional neural networks to segment lumbar intervertebral discs and characterize their biochemical composition using voxel-based relaxometry. The method was used to establish local associations with clinical measures of disability, muscle changes, and other symptoms of lower back pain. 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. Stratifying patients by disability grades revealed significant differences in the relaxation maps between minimal/moderate versus severe disability.


UMLS:C0449289


UMLS:C4305168


HP:0003419

The study aimed to identify serum biomarkers that correlate with vertebral endplate bone marrow lesions, also known as Modic changes (MC), which are 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, which are 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


UMLS:C0071997


NCBIGene:12268


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 adjacent 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 more severe disc degeneration during the mild-to-moderate stages.


UMLS:C2700066


UMLS:C0332985


UMLS:C1609607

The study presents a protocol for a Sequential Multiple-Assignment Randomization Trial for Low Back Pain (SMART LBP) within the Military Health System (MHS). The trial aims to assess the effectiveness of nonpharmacologic treatments for chronic low back pain. The trial has two phases, with participants initially randomized to receive either physical therapy (PT) or the Move2Health (M2H) program. Nonresponders to phase I treatment are then randomized to receive either a combination of M2H and PT or the Mindfulness-Oriented Recovery Enhancement (MORE) program. The primary outcome is the Patient-Reported Outcomes Measurement Information System pain interference computer-adapted test score.


UMLS:C0812167

Mindfulness-Oriented Recovery Enhancement (MORE) program


UMLS:C4511580

Vertebral endplate bone marrow lesions (Modic changes, MC)

The study aimed to understand 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 42 CLBP patients and 18 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.


NCBIGene:90427

Vertebral endplate bone marrow lesions (Modic changes, MC)


NCBIGene:90427

larger differences in patients with greater


NCBIGene:90427


UMLS:C0871582

The study presents a protocol for a trial evaluating the effectiveness of three forms of virtual reality (VR) for patients with chronic lower back pain (cLBP). The trial will randomize 360 patients into one of three arms: skills-based VR, distraction-based VR, and sham VR. 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:C0871582

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


UMLS:C0871582


UMLS:C0158712

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 resulting 3D dataset was used to describe global imbalance parameters in the patient population and to build a statistical shape model to describe global spine shape variations in preoperative deformity patients.


UMLS:C4704761


UMLS:C0448353

The study investigates the role of paraspinal musculature (PSM) in chronic low back pain (LBP) using standard MRI and chemical shift encoding-based water-fat MRI (CSE-MRI). The fat fraction (FF) of PSM, measured by CSE-MRI, showed excellent intra- and interreader agreement and was significantly associated with Goutallier classification (GC) at all spinal levels. The study suggests that CSE-MRI can detect early changes in PSM that are not detectable with GC. Both FF and GC were significantly associated with pain scores.


UMLS:C0424679


UMLS:C5548099


UMLS:C0448353

The study used hierarchical multiple factor analysis (hMFA) to analyze MRI data of paraspinal muscles (PSM) in relation to low back pain (LBP). The analysis was applied to two unique cohorts: astronauts with pre- and post-spaceflight data and a group of chronic LBP subjects and asymptomatic controls. The study 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 were more likely to experience increased pain after prolonged time in microgravity. Changes in PSM quality and structure between pre and post-spaceflight were also related to increased pain after prolonged microgravity. The study also confirmed previous research on the association of CEP damage and LBP diagnosis.


UMLS:C0242688


UMLS:C0448353


UMLS:C3686783


UMLS:C0332985

The study investigates the role of cartilage endplate (CEP) composition and vertebral bone marrow fat fraction (BMFF) in intervertebral disc degeneration in patients with chronic low back pain (cLBP). The study used MRI data from 60 patients and found that both CEP composition and vertebral BMFF were independently associated with disc degeneration. However, after adjusting for age, sex, and BMI, only CEP composition remained significantly associated with disc degeneration. The findings suggest that poor CEP composition plays a significant role in disc degeneration severity and can affect disc health both with and without deficits in vertebral perfusion.


NCBIGene:90427

Vertebral bone marrow fat fraction (BMFF)


UMLS:C0332985


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 in the PSMs varies according to symptoms and the severity of adjacent degenerative 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 findings suggest that the spatial distribution patterns of FI in the PSMs could serve as a potential diagnostic biomarker for cLBP.


UMLS:C0333575


UMLS:C0333575

Degenerative intervertebral disc (IVD) pathology


UMLS:C0224319


UMLS:C0394463

The study aims to investigate the effectiveness of a combined approach of physical therapy and mindfulness (MIND-PT) for post-surgical rehabilitation in patients with chronic low back pain (LBP) undergoing lumbar surgery. The study will compare an enriched pain management (EPM) pathway integrating physical therapy and mindfulness to usual care pain management (UC). The primary outcome will be the pain impact assessed with the Pain, Enjoyment and General Activity (PEG) scale, and 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.


UMLS:C0394463

Pain, Enjoyment and General Activity (PEG) scale


UMLS:C0242402


UMLS:C5444372

The Back Pain Consortium (BACPAC) Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs aim to standardize the collection, reading/grading, and storage of images for patients suffering from low back pain (LBP). The procedures are designed to improve understanding of pain mechanisms and facilitate patient phenotyping by providing standardized, non-invasive assessments of spinal pathologies.


UMLS:C1710183


UMLS:C1532547


UMLS:C0114463

The study discusses the development of a personalized medicine algorithm for chronic low back pain (cLBP) treatment. 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 optimize treatment selection for cLBP patients. Four leading, evidence-based treatments for cLBP were selected for the trial: duloxetine, acceptance and commitment therapy, a classification-based exercise and manual therapy intervention, and a self-management approach. These treatments were chosen based on their moderate to high level of evidence supporting a therapeutic effect and their belonging to different therapeutic classes.


UMLS:C3658321


UMLS:C4082302

Classification-based exercise and manual therapy intervention


UMLS:C0086969


MESH:D000069196

The paper reviews the potential connection between the gut microbiome and musculoskeletal pain. It discusses the role of various metabolites associated with inflammation and immune-metabolic response, which are known to contribute to musculoskeletal pain. The paper also explores modifiable factors like diet, lifestyle choices, exposure to prescription drugs, pollutants, and chemicals, and non-modifiable factors like gut architecture, genetics, age, birth history, and early feeding patterns that can influence the gut microbiome. The review suggests that the gut microbiome may play a crucial role in musculoskeletal health, and further research is needed to understand this connection.


UMLS:C0578570


UMLS:C0012155


UMLS:C0870811


UMLS:C0556027


UMLS:C0303747


UMLS:C0220806


UMLS:C0699819


UMLS:C1948182


UMLS:C0001779


HP:0033623


UMLS:C2067262


MESH:D000069196


UMLS:C1320105

The study investigates the value of shared medical appointments (SMAs) for patients with opioid use disorder (OUD) who are receiving buprenorphine/naloxone (B/N) treatment. The qualitative assessment revealed that SMAs foster a sense of accountability, shared identity, and supportive community among patients. The communication behaviors observed during the group visits, such as emotional support, probing about others' lives, venting, joking, and expressing gratitude, were found to be beneficial for the patients' recovery. However, certain behaviors like side conversations, tangential comments, and individual participants dominating group time could detract from the group experience.


UMLS:C0260173

The study aimed to test the effectiveness of Mindful Awareness in Body-oriented Therapy (MABT) as an additional treatment to buprenorphine for individuals with opioid use disorder (OUD). The results showed that the group that received MABT in addition to their usual treatment demonstrated an increase in interoceptive awareness skills, which was not observed in the control group. The study also found that MABT was well-received by the participants, indicating its potential as a feasible adjunct to medication treatment for OUD.


UMLS:C0260173


UMLS:C2985553

The study investigates the effects of Mindfulness-Oriented Recovery Enhancement (MORE) on opioid craving, pain, and positive affective state in individuals with opioid use disorder (OUD) and chronic pain undergoing methadone maintenance therapy (MMT). The results showed that participants who underwent MORE experienced significant improvements in craving, pain unpleasantness, stress, and positive affect compared to those who received treatment as usual (TAU). Furthermore, positive affect was associated with reduced craving, a relationship that was stronger in the MORE group than in the TAU group.


UMLS:C2985553


UMLS:C2215615


UMLS:C2906044

The study aimed to assess the appropriateness of a Peer Recovery Coach (PRC)-delivered adapted behavioral activation (BA) intervention to reduce problematic substance use in a medically underserved community in Baltimore. The study found that 30% of clients reported past problematic substance use and 70% met criteria for current use, most commonly cocaine and opioids. The study concluded that PRC-delivered BA could be acceptable and appropriate with suggested adaptations, including adding peer-delivered case-management and linkage to care alongside BA, and tailoring BA to include activities that are accessible and feasible in the community.


UMLS:C4535964


UMLS:C0946431


UMLS:C0808232

The paper discusses the manipulation of interoceptive pathways to improve symptoms in various disorders. The primary focus is on the respiratory system, and the paper outlines different pathways that can be manipulated at neural, behavioral, and psychological levels. These manipulations can change the representation of and attention to interoceptive signals, which can alter interconnected physiological systems and improve functioning and adaptive behavior. Interventions can alter interoception via neuromodulation of the vagus nerve, slow breathing to change respiratory rate and depth, or awareness processes such as mindfulness-based interventions.


UMLS:C0808232


UMLS:C0221161


UMLS:C1145171

The paper presents a systematic review of peer-delivered services for substance use in low- and middle-income countries (LMICs). The study found that peer-delivered services, provided by individuals with lived experience of substance use, may be effective in expanding access to treatment, supporting outcomes, and reducing stigma. The review included articles that spanned four continents and used both quantitative and qualitative methodologies. The results showed that some articles demonstrated positive impacts of the peer-delivered services, including reductions in risk behaviors and increases in infectious disease knowledge scores. However, many others showed no significant difference in outcomes between peer intervention and control groups. The study concludes that peer-delivered services may be feasible for addressing substance use and reducing infectious disease risk behaviors in LMICs.


UMLS:C1145171


UMLS:C2919490

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 treatment with Buprenorphine/Naloxone (Bup-Nal) 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 those in the detox group. The study found that therapy dose mediated the association between treatment arm and opioid abstinence, suggesting that extended Bup-Nal treatment may enhance abstinence, in part, through a mechanism of therapy facilitation, by increasing therapy dose during treatment.


UMLS:C1320105


UMLS:C5684302

The study investigates the feasibility and acceptability of the Mindful Recovery Opioid Use Disorder Care Continuum (M-ROCC), a 24-week mindfulness-based intervention (MBI) for adults with Opioid Use Disorder (OUD) prescribed buprenorphine/naloxone (B/N) treatment. The results showed that M-ROCC was feasible and acceptable, with high retention rates and increased mindfulness levels from baseline to 24 weeks. The increase in mindfulness was correlated with the frequency of informal mindfulness practice.


UMLS:C2985553

The study evaluated the effectiveness of Mindfulness-Oriented Recovery Enhancement (MORE) as an adjunct to methadone maintenance treatment (MMT) for individuals with opioid use disorder and chronic pain. The results showed that participants who received MORE in addition to their usual MMT showed significantly fewer days of illicit drug use, lower levels of craving, pain, physical and emotional limitations, depression, and anxiety through a 16-week follow-up compared to those who only received MMT. Participants in the MORE group also reported higher levels of well-being, vitality, and social functioning.


UMLS:C0556027

Medication for opioid use disorder (MOUD)

The study investigates the role of peer recovery specialists (PRSs) in reducing stigma-related barriers to medication for opioid use disorder (MOUD) treatment retention. The research found that stigma, particularly within ethno-racial minority communities, is a significant barrier to MOUD retention. PRSs, who have shared experiences in substance use and recovery, can play a key role in decreasing these barriers. The study also found that reducing stigma surrounding substance use disorder (SUD) and methadone treatment (MT) is critical for improving MOUD outcomes.


UMLS:C1626306


UMLS:C5550174

The study investigates the feasibility and acceptability of a mobile digital therapeutic, reSET-O, in treating opioid use disorder. reSET-O is a prescription digital therapeutic that delivers cognitive behavioral therapy modules and contingency management rewards. The study involved 15 individuals with opioid use disorder who were on buprenorphine treatment. Results showed that reSET-O was well accepted by both patients and providers, but adherence and retention in treatment remain areas for improvement.


UMLS:C5550174


UMLS:C0079843

The paper investigates the role of misinformation, stigma, and misconceptions in the low uptake of treatment for opioid use disorder among patients and providers. It was found that misinformation about opioids is prevalent among future healthcare providers, first responders, and pharmaceutical companies, which may affect treatment. Misconceptions about treatment efficacy and side effects, as well as stigma, have negatively impacted treatment uptake and adherence among individuals with opioid use disorder. The paper suggests that social media, education, and community involvement can help mitigate misinformation and address misconceptions about opioids and treatment options.


UMLS:C0277787


UMLS:C2717766


UMLS:C2364092


UMLS:C3179065


UMLS:C1292796


UMLS:C0009462


UMLS:C3864101

Peer recovery specialist-delivered behavioral activation and problem-solving approach

The study aimed to improve retention in methadone treatment for opioid use disorder (OUD) through a peer recovery specialist-delivered behavioral activation and problem-solving approach, called Peer Activate. The results showed high feasibility, acceptability, and fidelity of the intervention. The methadone retention rate was significantly higher in the Peer Activate group compared to a comparison cohort. There was also a significant reduction in substance use frequency and substance use-related problems among the Peer Activate participants.


UMLS:C3864101


UMLS:C2958211

The study investigates the effects of a 24-week trauma-informed program, Mindful Recovery OUD Care Continuum (M-ROCC), on patients undergoing office-based opioid treatment (OBOT) with buprenorphine. The program was found to reduce comorbid pain, anxiety, and substance use, including cocaine and benzodiazepines. It also increased mindfulness, interoceptive awareness, and self-compassion. The study suggests that M-ROCC could enhance retention and prevent overdose during OBOT. However, larger randomized controlled trials are needed to confirm these findings.


UMLS:C2958211


UMLS:C1531708

The study compared the clinical characteristics and in vivo confocal microscopy (IVCM) findings of patients with neuropathic corneal pain (NCP) due to refractive surgery (RS-NCP) and herpetic eye disease (H-NCP). The study found that the mean pain intensity score, quality of life scores, and alterations in DC density were similar in both groups. However, the mean total nerve density was lower in both RS-NCP and H-NCP groups compared to their respective controls.


UMLS:C0494081


UMLS:C0339223


UMLS:C1527312

The study investigates the effects of glucocorticoids (GC), specifically methylprednisolone (MP), on the immune response following major surgery. Using a high-dimensional mass cytometry approach, the researchers found that MP significantly altered immune cell signaling trajectories, particularly in the adaptive compartments of the immune system. However, key innate signaling responses associated with pain and recovery after surgery, such as STAT3 and CREB phosphorylation, were not affected by MP. This suggests that GCs have cell-specific and pathway-specific effects.


UMLS:C1527312

Adaptive compartments of the immune system


UMLS:C1527312


UMLS:C2960026

The PREDICT study aims to validate a novel biomarker signature, consisting of peak alpha frequency (PAF) and corticomotor excitability (CME), for predicting pain sensitivity. The study will use a human model of sustained myofascial temporomandibular pain, induced by intramuscular injection of nerve growth factor (NGF) into the right masseter muscle. The study will follow 150 healthy participants for 30 days as they develop and experience complete resolution of NGF-induced muscle pain. The primary outcome is pain sensitivity.


UMLS:C2210335


UMLS:C0027752


UMLS:C1450464

The study investigates the effectiveness and tolerability of the tricyclic antidepressant, nortriptyline, in treating neuropathic corneal pain (NCP). The results showed that nortriptyline was effective in relieving NCP symptoms in patients who had a centralized component of pain and had not responded sufficiently to other systemic and topical therapies. However, some patients discontinued treatment due to persistent side effects.


UMLS:C1450464


UMLS:C0355800

The study found that low-dose naltrexone (LDN) was effective in reducing pain and improving quality of life in patients with neuropathic corneal pain (NCP), a condition caused by damage or disease of the somatosensory nervous system that innervates the cornea. The treatment was well-tolerated, with common side effects including vivid dreams, headaches, and stomachache.


UMLS:C0355800


MONDO:0015290

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


MONDO:0015290


UMLS:C0161479


NCIT:C3137


MONDO:0024317

The study developed a classification system for chronic pain using multidimensional patient-reported symptoms and clustering analysis. The system was validated using three different patient subsets and was found to be effective in predicting follow-up assessments based on initial cluster assignment. The system could potentially improve clinical care by providing markers for personalized diagnosis and prognosis.


UMLS:C1881045


UMLS:C0027561


UMLS:C1552824


UMLS:C1696465

The study investigates the effects of placebo administration on immune function and its relationship with the endogenous opioid neurotransmitter system. The study involved 37 healthy human volunteers who were exposed to a standardized pain challenge. The results showed that placebo administration reduced the levels of the pro-inflammatory cytokine IL-18 during pain, and this reduction correlated with a decrease in pain scores. Furthermore, the reduction in IL-18 levels was associated 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 (IL-18) and its relationship with the endogenous opioid system.


UMLS:C1696465


PR:000001376


UMLS:C0205753


UMLS:C0027752

The study evaluated the reliability of peak alpha frequency (PAF) and corticomotor excitability (CME) as prospective cortical biomarkers for pain. Participants were given an injection of nerve growth factor (NGF) into the right masseter muscle, inducing sustained pain. PAF and CME were 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 exhibited either facilitation or depression of CME, with these changes being stable across sessions.


UMLS:C2960026


UMLS:C2210335

shows facilitation or depression in presence of


UMLS:C3508472

The study found that clinical questionnaires completed after mild traumatic brain injury (mTBI) can effectively predict headache improvement at 3 and 6 months, as well as the progression of the headache over the first 3 months. The study also found that reducing the questionnaire battery to only three, which assess post-concussive symptom load and biopsychosocialecologic factors, can provide a reasonable prediction accuracy for headache improvement.


UMLS:C3508472

can be predicted by clinical questionnaires


UMLS:C1827667


UMLS:C0814112


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 research found that LTA1-treated mice showed no neurotoxicity, unlike those treated with cholera toxin. The use of LTA1 in vaccines enhanced immune responses to inactivated virus antigen and improved protection against H1N1 influenza in mice. This protection was also observed in μMT mice lacking B-cells, suggesting that the mechanism of action does not require B-cells.


UMLS:C0440000


UniProtKB:Q99VQ4


PUBCHEM.COMPOUND:453626

The study presents the design and testing of a novel vaccine against fentanyl, an 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 against the hapten in mice. The antisera bound fentanyl and its analogues in vitro, with no cross-reactivity to other opioids like naloxone, naltrexone, methadone, or buprenorphine. In vivo, the vaccine shifted the antinociceptive dose-response curve of fentanyl to higher doses, demonstrating its potential to combat fentanyl-induced effects.


UNII:MWC0ET1L2P


MESH:D014612

shifts antinociceptive dose-response curve


PUBCHEM.COMPOUND:174548

The paper discusses the synthesis of a deuterated hapten, 6-AmHap, which is essential for a future study of residual hapten and stability of a hapten-protein conjugate. This hapten is chosen for a heroin vaccine that is now slated for a Phase 1 clinical trial. The vaccine, which connects the hapten 6-AmHap with an immunogenic carrier protein (tetanus toxoid, TT) through a trityl-protected 3-mercaptopropanamide linker, has been found to have activity against several opioids, including heroin and its metabolites, and importantly, does not affect alternate pain treatment medications such as methadone. The starting material for the synthesis of the deuterated 6-AmHap was Hydrocodone.


PUBCHEM.COMPOUND:174548


UMLS:C0772260


UMLS:C1714006

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 with adjuvants derived from the heat-labile toxin of E. coli, including dmLT and LTA1. The vaccine was delivered via intramuscular, sublingual, or intranasal methods. The results showed that the vaccine produced anti-fentanyl serum antibodies and antibody-secreting cells in the bone marrow. The highest levels of these antibodies were observed when the vaccine was adjuvanted with LTA1 or dmLT. The most effective blockade of fentanyl-induced analgesia and CNS penetration was achieved with sublingual dmLT or intranasal LTA1, correlating strongly to anti-FEN IgA.


CHEBI:84144


UMLS:C0314770


MESH:D014612


UMLS:C0085820


UMLS:C0071610


MESH:C083134

The study explores the synthesis of three novel opiate surrogates (6,14-AmidoHap, 14-AmidoMorHap, and 14-AmidoHerHap) as potential haptens for a heroin vaccine. These haptens were conjugated to the tetanus toxoid carrier protein and tested in mice for immunogenicity and efficacy. The results showed that none of the conjugates 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. Only the mice immunized with 14-AmidoHerHap were partially protected against heroin-induced antinociception.


MESH:C040241


MESH:C546895

The study investigates the impact of preexisting immunity to tetanus toxoid on the efficacy of a heroin vaccine (TT-6-AmHap) in mice. The vaccine is designed to generate high affinity antibodies to neutralize opioids before they reach the brain. The vaccine components include an opioid hapten (6-AmHap), a carrier protein (tetanus toxoid), and adjuvants (Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA). The mice were first primed with a diphtheria, tetanus, and acellular pertussis (DTaP) vaccine, then immunized with the TT-6-AmHap vaccine. The results showed that preexisting immunity to tetanus toxoid did not affect the immunogenicity and efficacy of the TT-6-AmHap vaccine.


MESH:C506643

Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA


UMLS:C3526553

Diphtheria, tetanus, and acellular pertussis (DTaP) vaccine


UMLS:C0003250

The study developed chimeric monoclonal antibodies (mAb) that can specifically bind with fentanyl and its analogs in the periphery, 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 that two mAb candidates with high binding affinities to fentanyl and its analogs were effective in engaging fentanyl in the periphery and blocking its effects in animals.


UMLS:C0003250


UMLS:C1714006


MESH:C472796

The study presents the design and synthesis of four haptens (1-AmidoMorHap, 1-AmidoMorHap epimer, 1 Amido-DihydroMorHap, and 1 Amido-DihydroMorHap epimer) as potential medications for opioid use disorder. These haptens are hydrolytically stable surrogates of heroin with the attachment site 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. The results showed that all TT-hapten conjugates induced high antibody endpoint titers against the targets, but only haptens 2 and 3 induced protective effects against heroin in vivo. The study also found that the chirality at C6 in these epoxymorphinans is crucial to their effectiveness.


UMLS:C3884417


UMLS:C0262593

The study investigates the impact of peripheral nerve injury on neuropathic pain and sympathetic activity in two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG). The results showed that both models led to neuroinflammatory changes in the sympathetic ganglia, characterized by 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:C0262593


UMLS:C5230021


UBERON:0002859


UMLS:C1704545

Low-velocity variable-amplitude spinal manipulation (LVVA-SM)

The study aimed to understand the analgesic mechanisms of low-velocity variable-amplitude spinal manipulation (LVVA-SM) in treating peripheral neuropathic pain. An animal model was developed using adult male Sprague-Dawley rats. The sciatic nerve tibial and common peroneal branches were transected, sparing the sural branch. The rats were then subjected to LVVA-SM or control conditions. The results showed that LVVA-SM reduced mechanical hypersensitivity but not cold hypersensitivity in the rats.


UMLS:C1704545


PR:000004141

The study found that Apolipoprotein A-I binding protein (AIBP) can prevent and reverse processes associated with neuroinflammatory-mediated spinal nociceptive processing. This is achieved through AIBP binding to Toll-like receptor-4 (TLR4) and increased binding of AIBP to activated microglia, which mediates selective regulation of lipid rafts in inflammatory cells. AIBP-mediated lipid raft reductions downregulate LPS-induced TLR4 dimerization, inflammatory signaling, and expression of cytokines in microglia. In mice, intrathecal injections of AIBP reduce spinal myeloid cell lipid rafts, TLR4 dimerization, neuroinflammation, and glial activation. AIBP also reverses established allodynia in mice in which pain states were induced by the chemotherapeutic cisplatin, intraplantar formalin, or intrathecal LPS, all of which are pro-nociceptive interventions known to be regulated by TLR4 signaling.


PR:000004141


MONDO:0043797

The study investigates the role of immune responses in the development of neuropathic pain following spinal cord injury (SCI) and the potential of exercise in modulating these responses. The researchers found that rats with SCI-induced pain had greater microglial activation in the C7-C8 dorsal horn and an increased number of macrophages in the dorsal root ganglia (DRG). Early exercise post-SCI was found to reduce microglial activation and the number of macrophages in the DRG, suggesting that exercise may prevent pain by modulating the injury-induced macrophage response in the DRG.


MONDO:0043797


UMLS:C0336916


PUBCHEM.COMPOUND:4829

The study investigates the role of sex in central neuropathic pain and its pharmacological inhibition in individuals with spinal cord injury (SCI). The analgesic efficacy of pioglitazone (PIO), a drug approved for diabetes treatment, and azithromycin (AZM), a commonly prescribed antibiotic with immunomodulatory properties, was tested in a mouse model of SCI pain. The results showed a sex-specific effect of PIO with significant antihyperalgesic effects in females, but not males. However, AZM was effective in both sexes. The findings support the use of PIO and AZM as novel therapies for SCI pain and emphasize the importance of considering sex as a biological variable in clinical and experimental SCI pain research.


PUBCHEM.COMPOUND:447043

has antihyperalgesic effects in both sexes


PUBCHEM.COMPOUND:4829


PUBCHEM.COMPOUND:447043

is a potential treatment for pain associated with


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 researchers found that acute inflammation triggers the accumulation of CP-AMPARs in the dorsal horn of the spinal cord, which contributes to acute inflammatory pain. The study also found that the CP-AMPAR antagonist IEM-1460 inhibited AMPAR-evoked Ca2+ transients after injury. The study concludes that CP-AMPAR inhibitors could be a promising class of agents for the treatment of chronic inflammatory pain.


UMLS:C0072899


MESH:C406748


MESH:C000718808


NCBIGene:394299

The study investigates the properties of the DOP-KOP heteromer agonist, 6'-guanidinonaltrindole (6'-GNTI), in comparison with agonists for DOP ([D-Pen2,5]-enkephalin [DPDPE]) and KOP (U50488) in peripheral sensory neurons. All three agonists inhibited PGE2-stimulated cAMP accumulation and activated ERK with similar efficacy. However, ERK activation by U50488 was Gi-protein mediated, while that by DPDPE or 6'-GNTI was Gi-protein independent. In vivo, all three agonists reduced thermal nociception. The study suggests that DOP-KOP heteromers exhibit unique signaling and functional regulation in peripheral sensory neurons and may be a promising therapeutic target for the treatment of pain.


NCBIGene:394299


MESH:C401320


UMLS:C3847834

The study investigates the role of Methylglyoxal (MG) in Painful Diabetic Neuropathy (PDN) in type 2 diabetes using db/db mice and C57BL/6J mice. The study found that administration of a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the enzyme that breaks down MG, reduced heat hypersensitivity in db/db mice. In C57BL/6J mice, MG administration resulted in signs of pain. The study concludes that MG and a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice, suggesting potential treatments for PDN in type 2 diabetes.


MESH:C000716787


UMLS:C0066384


PR:000000699


PR:000003751


PR:000013728


PR:000004141

The study reveals the significant role of apolipoprotein A-I binding protein (AIBP) in regulating cholesterol efflux and lipid rafts, which are cholesterol-rich and sphingomyelin-rich membrane domains. AIBP mediates selective cholesterol efflux, particularly through binding to toll-like receptor-4 (TLR4) in activated macrophages and microglia, thereby reversing lipid raft increases in activated cells. AIBP also regulates the function of vascular endothelial growth factor receptor-2, Notch1, and TLR4. In animal models, AIBP deficiency leads to accelerated angiogenesis, increased inflammation, and exacerbated atherosclerosis. The administration of recombinant AIBP reduces inflammation and persistent pain in a mouse model of chemotherapy-induced polyneuropathy and reduces lipopolysaccharide-induced acute lung injury. These findings suggest potential therapeutic applications for AIBP in angiogenic and inflammatory diseases.


PR:000004141

Vascular endothelial growth factor receptor-2


PR:000004141


PR:000004141

Lipopolysaccharide-induced acute lung injury


UMLS:C0754471

The study investigates the role of TWIK-related spinal cord K+ (TRESK) channel in trigeminal pain processing. The research used TRESK global knock-out mice as a model system and found that the loss of TRESK increased the intrinsic excitability of small-diameter nociceptors, especially those that do not bind to isolectin B4 (IB4-). This resulted in hyper-excitation of the small IB4- dural afferent neurons. Both male and female TRESK knock-out mice exhibited more robust trigeminal nociceptive behaviors, including headache-related behaviors. The study concludes that endogenous TRESK activity regulates trigeminal nociception, likely through controlling the intrinsic excitability of TG nociceptors, and that genetic loss of TRESK significantly increases the likelihood of developing a headache.


UMLS:C0754471


MESH:D063388

The paper discusses the role of endocannabinoids, a type of neurotransmitter system, in providing short-term pain relief following spinal manipulative therapy, a treatment used for chronic pain. The research suggests that endocannabinoids contribute to the analgesic effect of this therapy, and understanding their involvement could improve the clinical efficacy of the treatment.


MESH:D063388


UMLS:C2073787


UMLS:C5200744

The study presents a pH-responsive, soft polymeric nanoparticle designed to target acidified endosomes and inhibit endosomal signalling events that lead to chronic pain. In chronic pain, the substance P (SP) neurokinin 1 receptor (NK1R) moves from the plasma membrane to acidified endosomes, where it signals to maintain pain. The nanoparticles enter cells via clathrin- and dynamin-dependent endocytosis and accumulate in NK1R-containing endosomes. When injected into rodents, the nanoparticles, which contain the FDA-approved NK1R antagonist aprepitant, inhibit SP-induced activation of spinal neurons and thus prevent pain transmission. This treatment results in complete and persistent relief from nociceptive, inflammatory, and neuropathic nociception, providing a non-opioid treatment option for chronic pain.


NCBIGene:6869

Substance P (SP) neurokinin 1 receptor (NK1R)


NCBIGene:6869


UMLS:C5200744


PUBCHEM.COMPOUND:135413536


UMLS:C5200744

Nociceptive, inflammatory, and neuropathic nociception


UMLS:C0815002

Central nucleus of the amygdala (GABACeA)

The study identifies a neural pathway that may be responsible for comorbid pain in depression (CP). This pathway involves GABAergic neurons from the central nucleus of the amygdala (GABACeA) projecting to glutamatergic neurons in the parafascicular nucleus (GluPF), which then relay directly to neurons in the second somatosensory cortex (S2). Enhanced inhibition of this pathway is found in mice exhibiting CP symptoms. Using chemogenetic or optogenetic approaches to reverse this pathway alleviates CP symptoms.


CL:0000617


UMLS:C0815002


UMLS:C3665472


UMLS:C3494301


UMLS:C1167250

The paper discusses the role of lipid rafts in glial cells and their contribution to neuroinflammatory sensitization of central pain signaling pathways. The authors introduce the concept of an "inflammaraft" (i-raft), which are enlarged lipid rafts that contain activated receptors and adaptor molecules, initiating inflammatory signaling and cellular response. The study highlights the involvement of inflammatory receptors, redox molecules, and ion channels in inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in inflammaraft maintenance and disruption. The paper suggests that targeting inflammarafts could lead to new therapies for neuropathic pain states and other neuroinflammatory conditions.


UMLS:C1302375


UMLS:C0368909


CHEBI:26739


UMLS:C5544451


UMLS:C1411976


HP:0012531

The study found that short-term pain, induced by an injection of complete Freund's adjuvant (CFA), decreased voluntary morphine intake in rats. This decrease was blocked by pre-treatment with indomethacin, a non-opioid inhibitor of pain. In rats with steady morphine self-administration, the protein level of GluA1 subunits of glutamate AMPA receptors was increased in the central nucleus of the amygdala (CeA), while that of GluA2 was decreased. This resulted in an increased GluA1/GluA2 ratio. Pain decreased this ratio. Microinjection of NASPM, an inhibitor of GluA1-AMPARs, into CeA inhibited morphine intake. Overexpression of GluA1 protein in CeA maintained morphine intake at a higher level and reversed the pain-induced reduction in morphine intake. This suggests that CeA GluA1 promotes opioid use and its upregulation increases opioid consumption, counteracting the acute inhibitory effect of pain on opioid intake.


UMLS:C0982211


PR:000008233


PR:000008234


UMLS:C0132709


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 dorsal root ganglions (DRGs) after spinal nerve ligation (SNL) in mice. SNL increased the amount of Nrcam+10 and decreased the level of Nrcam-10. An antisense oligonucleotide (ASO) targeting exon 10 of Nrcam gene repressed Nrcam+10 expression and increased Nrcam-10 expression in DRG cell culture. Injections of Nrcam ASO attenuated SNL-induced pain hypersensitivities. The study concludes that the relative levels of alternatively spliced Nrcam variants are critical for neuropathic pain genesis.


NCBIGene:4897


UMLS:C0078976


PR:000001516

expression increased following nerve injury

The study found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Inhibition of GPR160 in the spinal cord prevented and reversed neuropathic pain in rodents without altering normal pain response. The study also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in the spinal cord attenuated neuropathic pain, while exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB).


NCBIGene:71862


NCBIGene:9607


UMLS:C3653444

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 CGRP-targeting drugs have shown a remarkable safety profile, which may be due to the redundancy of peptides within the CGRP family and a second CGRP receptor that may compensate for reduced CGRP activity.


UMLS:C3653444


UMLS:C0108066


PR:000014888

The study identifies the histone deacetylase Sirtuin 1 (SIRT1) in the central amygdala as a key regulator in controlling the development of comorbid emotional disorders, which underlie individual vulnerability to chronic pain. The study found that animals vulnerable to developing behaviors of anxiety and depression under pain conditions displayed reduced SIRT1 protein levels in the central amygdala. Overexpression of local SIRT1 reversed this vulnerability, while knockdown of local SIRT1 mimicked the pain effect. The action of SIRT1 was associated with CaMKIIα downregulation and deacetylation of histone H3 lysine 9 at the CaMKIIα promoter. The study suggests that SIRT1 may serve as a potential therapeutic molecule for individualized treatment of chronic pain with vulnerable emotional disorders.


PR:000014888


UMLS:C0079189

The paper discusses the role of cytokines, a type of soluble mediator, in the development and maintenance of inflammatory and neuropathic pain. The study suggests that cytokines facilitate nociceptive processing at all levels of the neuraxis, including peripheral nociceptor termini, dorsal root ganglia, spinal cord, and supraspinal areas. This action of cytokines throughout the neuraxis is believed to play key roles in the induction of pain and the maintenance of the facilitated states of pain behavior generated by tissue injury/inflammation and nerve injury.


UMLS:C0079189


UMLS:C1302977

The study introduces a new method, the operant plantar thermal assay (OPTA), for measuring thermal pain tolerance in mice. The OPTA requires mice to make a decision to obtain a reward under thermally adverse conditions. The study found that female mice showed greater temperature-dependent tolerance than males. The study also found that neuropathic pain, induced by chronic constriction injury (CCI), increased thermal tolerance, while inflammation, induced by complete Freund's adjuvant (CFA), had no effect. The administration of clonidine increased thermal tolerance in both injured and sham animals, while the non-steroidal anti-inflammatory meloxicam reduced thermal pain tolerance.


UMLS:C0332680


MESH:C114843


UMLS:C0949270


PUBCHEM.COMPOUND:54677971


UMLS:C0262593

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


NCBIGene:14955


NCBIGene:14955

contributes to development and maintenance of


PR:000008233

The paper suggests that GluA1, a protein found in the central amygdala, has a dual role in pain perception and opioid withdrawal. It increases pain but inhibits the aversion typically associated with opioid withdrawal.


PR:000008233


NCBIGene:4204

The study found that the DNA methyl-CpG binding protein 2 (MeCP2) plays a crucial role in the transgenerational transmission of chronic pain. In a female mouse model of chronic pain, offspring showed significant pain sensitization, which correlated with increased MeCP2 expression in primary somatosensory cortical (S1) glutamate neurons. Manipulating MeCP2 expression in these neurons in the maternal mice affected the pain sensitization in the offspring. The study also found that MeCP2 regulated the expression of a wide range of genes in these neurons, suggesting its importance in pain transgenerational transmission.


NCBIGene:4204

Primary somatosensory cortical (S1) glutamate neurons


NCBIGene:4204


UMLS:C3670482

The study found that Toll-like receptor 7 (TLR7) contributes to neuropathic pain. Peripheral nerve injury led to a significant increase in the expression of TLR7 in mouse injured dorsal root ganglion (DRG). Blocking this increase alleviated pain hypersensitivities. Conversely, mimicking this increase led to augmented responses to stimuli and induced spontaneous pain. The increased TLR7 activated the NF-κB signaling pathway, suggesting that TLR7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons.


PR:000001158


PR:000008264

The paper discusses the sensitization of Group II metabotropic glutamate receptor expressing neurons in the anterior cingulate cortex following inflammatory and neuropathic pain.


UMLS:C0027882


UMLS:C0234251


NCIT:C96210


UMLS:C0039038

The study investigates the effect of local sympathectomy on chemotherapy-induced neuropathic pain in mice. The procedure, which involves cutting the ipsilateral gray rami entering the spinal nerves near the L3 and L4 dorsal root ganglia, was performed on mice receiving intraperitoneal injections of the chemotherapeutic drug paclitaxel. The results showed that sympathectomy led to a fast recovery from mechanical allodynia and prevented the development of cold allodynia. The procedure also induced transcriptional increases in dorsal root ganglia of macrophage markers and anti-inflammatory cytokines, such as the transforming growth factor-β. Depletion of monocytes/macrophages and blockade of transforming growth factor-β signaling reversed the relief of mechanical allodynia by sympathectomy. Exogenous transforming growth factor-β was sufficient to relieve mechanical allodynia after paclitaxel, and transforming growth factor-β signaling regulated neuronal activity in dorsal root ganglia.


UMLS:C0039038


UMLS:C0040690


UBERON:0000979

The study found that tibia fractures can induce an adaptive autoimmune response, characterized by germinal center formation in popliteal lymph nodes and T follicular helper cell (Tfh) dependent B cell activation, leading to nociceptive sensitization within 3 weeks. This response was found to be dependent on the production of IgM. The study also found that treating fracture mice with the Tfh signaling inhibitor FK506 reduced germinal center reactions, IgM levels, and nociceptive sensitization.


UBERON:0010754


CL:0002038


CL:0000236


PR:000050257


MESH:C107029


UMLS:C0303223

The study found that general anesthesia (GA) can suppress pain by activating a specific group of GABAergic neurons in the central amygdala (CeAGA neurons) of mice. These neurons are activated by different GA drugs and have a basal activity that reflects the internal state of the animal. When these neurons were activated, they suppressed pain and abolished neuropathic pain-induced mechanical hypersensitivity. In contrast, inhibiting these neurons exacerbated pain and cancelled the analgesic effect of low-dose ketamine. The researchers suggest that CeAGA neurons could be a potential therapeutic target for chronic pain relief.


UMLS:C0815002


UMLS:C0700541

analgesic effect cancelled when GABAergic neurons are inhibited


MONDO:0043797

The study investigates the effect of sex on neurodegeneration, locomotor impairment, and neuropathic pain following a spinal cord injury (SCI) in male and female C57BL/6 mice. The study found that while motor function was largely similar between sexes, all males and only half of the females recovered plantar stepping. The rostral-caudal lesion length was shorter in females than in males. However, there were no significant differences in behavioral signs of neuropathic pain between sexes.


MONDO:0043797


UMLS:C0006669

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). The researchers found a large overlapping CGRP and P2X3R neuronal subpopulation in human lumbar DRG that was not present in mouse. They also found 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:C0382265


UMLS:C1563722


UMLS:C0034792


UMLS:C0032824


UMLS:C0037492


UMLS:C2331010

The study found that a localized sympathectomy, which involves cutting the gray rami containing sympathetic postganglionic axons, reduced mechanical hypersensitivity in two different rat neuropathic pain models. This procedure also reduced functional and anatomical measures of regeneration, as well as the expression of growth-associated protein 43 (GAP43), a protein related to regeneration. In addition, the sympathectomy reduced the formation of neuromas and the density of macrophages in the sensory ganglia and peripheral nerve. These findings suggest that sympathetic nerves may locally affect immune function and that managing pain in neuropathic conditions without inhibiting peripheral nerve regeneration is a challenge.


UMLS:C2331010


NCBIGene:36727

The study investigates the role of cyclin-dependent kinase 5 (Cdk5) in neuropathic pain. Cdk5 and its activators p35 and p39, which are expressed in spinal nerves, dorsal root ganglia, and the dorsal horn of the spinal cord, are found to have increased expression/activity in neuropathic pain conditions. Cdk5 is regulated through its own phosphorylation, through increasing p35's interaction with Cdk5, and through cleavage of p35 into p25. Cdk5 affects various proteins involved in pain signaling, including channels (eg, transient receptor potential cation channel and voltage-gated calcium channel), proteins involved in neurotransmitter release (eg, synaptophysin and collapsin response mediator protein 2), and receptors (eg, glutamate, purinergic, and opioid). Therefore, Cdk5 could be a potential target for treating neuropathic pain conditions.


UMLS:C0662945


UMLS:C0666104


NCBIGene:36727

Transient receptor potential cation channel


NCBIGene:36727


UMLS:C0384842

The study provides insights into 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 primary afferent neurons and a subpopulation of small, excitatory, glutamatergic/somatostatinergic interneurons (Y1-INs) in the dorsal horn. The selective removal of spinal Y1-INs with an NPY-conjugated saporin neurotoxin reduces peripheral nerve injury-induced hypersensitivity. 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-INs is a significant mechanism of endogenous analgesia. This mechanism can be replicated with pharmacological approaches, such as the administration of Y1 agonists, to inhibit hypersensitivity and spinal neuron activity in rodent models of neuropathic, inflammatory, and postoperative pain. Activation of Y1 also inhibits mechanical- and histamine-induced itch. The findings suggest that Y1-INs could be a potential therapeutic target for the development of NPY-Y1 agonists to treat chronic pain and itch.


UMLS:C0384842


MESH:C108165


UMLS:C2917359

Neuropathic, inflammatory, and postoperative pain


UMLS:C2917359


UMLS:C1511372

The study investigates the neuropathic phenotype of the K/BxN transgenic mouse, which develops spontaneous autoimmune arthritis. Both male and female mice display severe tactile allodynia, which is reduced by gabapentin but not by ketorolac. In the dorsal horn, both genders show increased GFAP+ astrocytic cells, but only males show an increase in Iba1+ microglia. In the dorsal root ganglia (DRG), there is an increase in CGRP+, TH+, and Iba1+ (macrophage) labeling, but no increase in ATF3+ cells. At the ankle, there is increased CGRP+, TH+, and GAP-43+ fiber synovial innervation. These findings suggest that the adult K/BxN transgenic arthritic mice display a neuropathic phenotype, which is consistent with the analgesic pharmacology seen in this animal model.


UMLS:C0751213


UMLS:C0228090


CL:0002628


UMLS:C0006669


CL:0002057


PR:000039003


UMLS:C1267208


PR:000009780

The study found that legumain (Lgmn), a cysteine protease, cleaves protease-activated receptor-2 (PAR2) in the acidic microenvironment of oral squamous cell carcinoma (OSCC), causing pain. Lgmn was found to be activated in OSCC patient tumors compared to normal oral tissue. Lgmn evoked pain in wild-type female mice but not in mice lacking PAR2 in NaV1.8-positive neurons or in mice treated with a Lgmn inhibitor, LI-1. Lgmn caused PAR2-dependent hyperexcitability of trigeminal neurons and activated PAR2 by biased mechanisms to induce calcium mobilization, cAMP formation, and activation of protein kinase A (PKA) and protein kinase D (PKD), but not β-arrestin recruitment or PAR2 endocytosis.


PR:000009780


PR:000009780

does not recruit or induce endocytosis of


NCBIGene:729230

The study investigates the role of CCR2-expressing macrophages in a mouse model of low back pain and radiculopathy. The researchers found that local inflammation of the dorsal root ganglia (DRG) induced pain behaviors in mice, which were dominated by increases in CCR2+ macrophages. 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 included global CCR2 knockout, systemic injection of INCB3344 (a specific CCR2 blocker), and intravenous injection of liposomal clodronate. The study suggests a key role for the CCR2/CCL2 system in establishing the pain state in this model of inflammatory low back pain and radiculopathy.


UBERON:0000044


NCBIGene:6347


UMLS:C3827110


UMLS:C0935779


MONDO:0024317

The paper discusses the role of neuroimmune signaling in chronic pain conditions such as low back pain, arthritis, persistent post-surgical pain, fibromyalgia, and neuropathic pain disorders. It emphasizes that the interaction between immune cells, glia, and neurons is crucial for the onset and persistence of chronic pain. The paper also discusses recent advancements in understanding these neuroimmune signaling mechanisms and potential therapeutic targets in rodent models of chronic pain. Additionally, it mentions new technologies to study, diagnose, and quantify the neuroimmune contributions to chronic pain in patients.


MONDO:0024317


MONDO:0011441

The study suggests that complex regional pain syndrome (CRPS) may be 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 lacking B cells. The study also found that complement component C5a and its receptor expression increased in skin and spinal cord after fracture, predominantly on dermal macrophages and spinal microglia. The pronociceptive effects of IgM were blocked by a C5a receptor antagonist (PMX53) or a global cytokine inhibitor (pentoxifylline). Chronic CRPS patient IgM (but not IgG) caused nociceptive sensitization in muMT fracture mice. The researchers suggest 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, leading to proinflammatory cytokine expression contributing to nociceptive sensitization in the injured limb.


PR:000050257


PR:000004904


PR:000030035

The paper discusses the role of G protein-coupled receptors (GPCRs) in chronic pain associated with digestive system disorders, inflammation, and cancer. The study suggests that GPCRs, when activated by mediators from injured tissues, can lead to sensitization of ion channels and acute hyperexcitability and nociception. Sustained agonist release can cause GPCR redistribution to endosomes, where persistent signaling regulates activity of channels and genes that control chronic hyperexcitability and nociception. The paper also discusses the potential of endosomally targeted GPCR antagonists, biased agonists of µ-opioid receptors (MOPrs), and allosteric modulators of GPCRs in providing superior pain relief. The study also highlights the potential of GPCR dimers as distinct therapeutic targets for nociception.


UMLS:C0022009


NCBIGene:212541


MESH:D011992

site of GPCR redistribution in chronic pain


UMLS:C5203045

potential distinct therapeutic targets for


UMLS:C1257975

Chemotherapy-induced peripheral neuropathy (CIPN)

The study demonstrates 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 includes mechanical allodynia, spontaneous pain, and loss of intraepidermal nerve fibers (IENF) in the paw. The resolution of CIPN is associated with the normalization of the cisplatin-induced decrease in mitochondrial bioenergetics in DRG neurons. The MSC enter the meninges of the brain, spinal cord, and peripheral lymph nodes to promote IL-10 production by macrophages. The reversal of CIPN symptoms critically depends on IL-10 production. MSC from IL-10 knockout animals are not capable of reversing the symptoms of CIPN. Moreover, wild type MSC do not reverse CIPN in mice lacking IL-10 receptors on peripheral sensory neurons.


UMLS:C1257975


NCBIGene:3586


UMLS:C0262593

The paper discusses neuropathic pain, a common clinical disorder that significantly impacts the quality of life of patients. The study focuses on the downregulation of opioid receptors in primary afferent neurons following peripheral nerve trauma, which limits the effectiveness of opioids in treating this disorder. The paper explores the molecular mechanisms behind this downregulation, including alterations in epigenetic modifications (DNA methylation, histone methylation, and microRNAs), expression of transcription factors, post-transcriptional modifications (RNA methylation), and protein translation initiation in the neurons of the dorsal root ganglion (DRG). The study suggests that understanding these mechanisms could provide new avenues for the prevention and treatment of neuropathic pain.


GO:2000475


UMLS:C0262593


CL:0000084

The paper discusses the role of T cells in the suppression of pain, suggesting that they play a key role in resolving pain. The study also suggests that dysregulation of certain immune functions may lead to chronic pain. The paper proposes that stimulating the endogenous immune-mediated resolution pathways could be a potent approach to treat chronic pain.


UMLS:C2371094


GO:0140403

Endogenous immune-mediated resolution pathways


PR:000006680

The study investigates the role of non-SUMOylated collapsin response mediator protein 2 (CRMP2) in the functional expression of the voltage-gated sodium channel NaV1.7, which is crucial in neuronal excitability and pain signaling. The research found that non-SUMOylated CRMP2 forms a complex with endocytic proteins Numb, Eps15, and Nedd4-2 to promote the endocytosis of NaV1.7. Inhibiting clathrin assembly in nerve-injured mice precipitated mechanical allodynia, a type of neuropathic pain. The expression of Numb, Nedd4-2, and Eps15 was not modified in the dorsal root ganglia (DRG) of the mice. Silencing these proteins in DRG neurons restored the loss of sodium currents.


PR:000006680


UMLS:C5203045


UMLS:C1135987


PR:000011505


NCBIGene:226025

The study investigates the role of Transient receptor potential melastatin 3 (TRPM3), a heat-activated ion channel in primary sensory neurons, 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 induced by chronic constriction injury (CCI) of the sciatic nerve in wild-type mice, but not in TRPM3-/- mice. The study also found that genetic deletion or inhibitors of TRPM3 reduced the increase in the levels of the early genes c-Fos and pERK in the spinal cord and dorsal root ganglia (DRGs) in CCI mice, suggesting spontaneous activity of the channel. The findings indicate a role for TRPM3 in heat hypersensitivity and spontaneous pain after nerve injury.


NCBIGene:226025


PUBCHEM.COMPOUND:5280804


PUBCHEM.COMPOUND:4909


UMLS:C5441949


NCBIGene:822051


UMLS:C1563722

The study focuses on the role of Transient Receptor Potential (TRP) ion channels in orofacial pain, which includes 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 study also highlights the distinct peripheral and central pain processing and different sensitivities of the orofacial sensory system from the spinal sensory system.


NCBIGene:83810


PR:000000699


PR:000001068


PR:000001719


UBERON:0007641


UMLS:C0228066


UMLS:C0109529

The study investigates the effects of a neurokinin 1 receptor (NK1R) antagonist, Spantide I (Span), conjugated to cholestanol (Span-Chol), on pain relief. 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, 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


UMLS:C4086508

The study investigates the role of interleukin 6 (IL-6) signaling in the development of adaptive immune responses and nociceptive sensitization in a murine tibia fracture 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. The study also found that the administration of anti-IL-6 antibodies reduced nociceptive and vascular changes after fracture and inhibited lymphadenopathy.


UMLS:C4086508


UMLS:C0563227

The study reviews the mechanisms and pathways of pain modulation by light exposure, known as photobiomodulation. It was found that cutaneous application of red light (660 nm) can reduce pain in neuropathies and complex regional pain syndrome-I, but visual application of the same wavelength can exacerbate migraine headaches and cause functional pain in animal models. Conversely, visual exposure to green light can reduce pain in conditions like migraines and fibromyalgia. Both routes of exposure cause changes in the brainstem, spinal cord, dorsal root ganglia, and nociceptors.


UMLS:C0563227


UMLS:C1306567


PR:000013429

The study found that intermittent parathyroid hormone (iPTH) can reduce osteoarthritis pain by inhibiting sensory innervation, deterioration of subchondral bone, and degeneration of articular cartilage in a mouse model. The iPTH treatment also reduced the level of prostaglandin E2 in the subchondral bone of the mice and regulated uncoupled subchondral bone remodeling caused by increased transforming growth factor β signaling. The effects of iPTH were found to be specifically through the PTH type 1 receptor in Nestin+ mesenchymal stromal cells.


PR:000013429


UMLS:C1175999


UMLS:C0220833

The study investigates the effects of Dimethyl fumarate (DMF) on Complex regional pain syndrome (CRPS) in a murine model. CRPS is a painful condition often caused by surgery or trauma to a limb, and is associated with both innate and adaptive immunological changes. DMF, which activates antioxidant systems and suppresses immune system activation, was hypothesized to reduce nociceptive, functional, and immunological changes in a model of CRPS. The study found that DMF administration prevented nociceptive sensitization, reduced uneven hindlimb weight bearing, and reduced the accumulation of markers of oxidative stress, activation of innate immune mediator production, lymph node hypertrophy, and the accumulation of IgM in fractured limbs. Interestingly, the effects of DMF were largely unchanged in Nrf2 null mutant mice, suggesting that the Nrf2 transcription factor is not required for DMF's effects.


UMLS:C0220833


PR:000002102

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 epigenome engineering approaches based on CRISPR-dCas9 and zinc finger proteins to repress NaV1.7 in primary afferents at the spinal level. The efficiency of NaV1.7 repression was first optimized in vitro in Neuro2A cells. The epigenome engineering platforms were then delivered via adeno-associated viruses (AAVs) to assess their effects in three mouse models of pain. The results showed effective repression of NaV1.7 in lumbar dorsal root ganglia, reduced thermal hyperalgesia in the inflammatory state, decreased tactile allodynia in the neuropathic state, and no changes in normal motor function in mice.


MESH:D000076987


UMLS:C0078803


UMLS:C1564874


PR:000002102


NCBIGene:9607

Cocaine- and amphetamine-regulated transcript (Cartpt)

The peptide encoded by the cocaine- and amphetamine-regulated transcript (Cartpt) gene, known as CART peptide (CART), has been recognized since 1981. The gene encoding CART was identified in 1995. The CART peptide has been linked to ingestive behaviors, reward behaviors, and pain sensation. Despite the significance of CART, the full potential for this peptide or its analogs to be developed into therapeutic agents remained unrealized due to the absence of an identified receptor. Recently, the G protein-coupled receptor (GPCR), GPR160, has been identified as a receptor for CART, opening up potential for the development of pharmcotherapies targeting GPR160.


NCBIGene:9607


CL:0000235

The study found that macrophages (MΦ) residing in the sciatic nerve play a significant role in cancer-induced pain. Depletion of these resident macrophages (rMΦ) in mice reduced pain sensitivity caused by the injection of melanoma or lung carcinoma cells. The study also found that MΦ-colony stimulating factor (M-CSF) was upregulated in the sciatic nerve trunk and contributed to cancer-induced pain through rMΦ expansion, activation of transient receptor potential ankyrin 1 (TRPA1), and oxidative stress. The deletion of Trpa1 revealed that Schwann cell TRPA1 is crucial for sciatic nerve rMΦ expansion and pain-like behaviors. The study concluded that a feed-forward pathway involving M-CSF, rMΦ, oxidative stress, and Schwann cell TRPA1 signals cancer-induced pain.


NCBIGene:8989


MESH:C062290

The study investigates the effectiveness of a fentanyl analogue, NFEPP, which preferentially activates the µ-opioid receptor (MOPr) in acidified diseased tissues, in treating pain in a preclinical model of inflammatory bowel disease (IBD) without side effects in healthy tissues. The results show that NFEPP inhibited pain responses in mice with colitis but not in control mice, consistent with acidification of the inflamed colon. Unlike fentanyl, NFEPP did not decrease defecation, cause respiratory depression, or induce hyperactivity in mice with colitis. The study concludes that NFEPP preferentially activates MOPr in acidified microenvironments of inflamed tissues to induce pain relief without causing respiratory depression, constipation, and hyperactivity.


MESH:C062290


UMLS:C1714006


UMLS:C0039198

The study investigates the effect of low-dose interleukin-2 (ld-IL2) and regulatory T (Treg) cells on mechanical allodynia, a condition of heightened sensitivity to pain, in a mouse model of sciatic nerve injury. The results show that treatment with ld-IL2 or adoptive transfer of Treg cells can significantly reduce the severity of allodynia. The study also found that ld-IL2 increased the frequency of Treg cells in the injured sciatic nerves, suggesting that the injured nerve is the site of action for ld-IL2.


UMLS:C0185279

The study investigates the effect of a localized "microsympathectomy" and the manipulation of CCL2 (monocyte chemoattractant protein 1) in a rat tibial nerve crush model of neuropathic pain. The results show that microsympathectomy and localized siRNA-mediated knockdown of CCL2 in the lumbar dorsal root ganglion led to partial improvement of mechanical hypersensitivity and guarding behavior, reduction of regeneration markers growth-associated protein 43 and activating transcription factor 3, and reduction of macrophage density in the sensory ganglia and regenerating nerve. The study suggests that local sympathetic effects on neuropathic pain may be mediated largely by the effects on expression of CCL2, which in turn regulates the regeneration process.


NCBIGene:6347


MONDO:0024317

The paper discusses the challenge of chronic pain, a disabling disease with limited treatment options. The authors propose a multi-institutional collaboration to better understand the cells and networks of pain in humans, which could potentially lead to improved therapeutic development.


MONDO:0024317


UMLS:C1522647


NCBIGene:7099

The study found that neuroinflammation, a major component in the transition to and perpetuation of 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 in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice. 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.


NCBIGene:19


PR:000004141


NCBIGene:9607

The paper discusses the diverse pharmacological actions of the Cocaine- and amphetamine-regulated transcript peptide (CARTp) in 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 or its analogs. The CARTp-GPR160 interaction is essential for the circadian regulation of appetite and thirst and for the transmission of nerve injury-induced pain. Further molecular approaches are being used to uncover additional physiologically relevant actions of this ligand/receptor pair.


NCIT:C26791

The study investigates the role of FTO (fat-mass and obesity-associated protein), an N6-methyladenosine demethylase, in hemorrhage-induced thalamic pain. The research found that FTO expression was increased in the thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase). The administration of meclofenamic acid (an FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of Ftofl/fl mice reduced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity. Conversely, thalamic microinjection of AAV5 expressing FTO increased TLR4 expression and elicited hypersensitivities to various stimuli. The findings suggest that FTO stabilizes TLR4 upregulation in thalamic neurons, contributing to hemorrhage-induced thalamic pain.


PR:000007694


UMLS:C0025041


PR:000029877


UMLS:C0006669

The CGRP system, part of the calcitonin family of peptides, is a significant target for migraine treatment. However, not all migraine sufferers respond to anti-CGRP treatments, indicating the need for additional targets. Other peptides in the calcitonin family, including calcitonin, amylin, adrenomedullin, and adrenomedullin 2, show pro-nociceptive and anti-nociceptive actions in primary headache conditions like migraine. These peptides and their receptors may be useful in treating migraine and other pain disorders.


UMLS:C0544402


MESH:D002116


PR:000008875


UMLS:C0215825


UMLS:C0054487

The study investigates the role of mitochondrial calcium uniporter in painful diabetic neuropathy (PDN), a complication affecting 25% of diabetic patients. The researchers found that mitochondrial fission proteins were elevated in dorsal root ganglion (DRG) neurons in mice with PDN. They also observed increased calcium signaling in DRG nociceptors and fragmented mitochondrial morphology. By selectively deleting the mitochondrial calcium uniporter, they were able to restore normal mitochondrial morphology, prevent axonal degeneration, and reverse mechanical allodynia in the mouse model. The study suggests that targeting calcium entry into nociceptor mitochondria could be a potential therapeutic approach for PDN.


PR:000010366


CHEBI:39124


MESH:D008928


UMLS:C0054487


NCBIGene:11535

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 researchers synthesized and characterized mouse adrenomedullin, adrenomedullin 2, and βCGRP, and mouse CTR with or without mouse RAMPs. They found that the pharmacology of these receptors in mice is subtly different from that in humans, with mouse receptors showing less discrimination between ligands. This finding poses challenges for translating findings from mice to humans and underscores the need for new ligands to differentiate between these complexes.


UMLS:C1447773


NCBIGene:76701


PR:000001068

The study focuses on the role of the Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel in acute and chronic itch. TRPV4, which is expressed in ganglion sensory neurons and various skin cells, has been relatively understudied in the context of itch modulation. However, recent evidence suggests that TRPV4 contributes to acute and chronic disease-associated itch. The exact cellular and molecular mechanisms of TRPV4's involvement in itch are still not fully understood.


PR:000001068


UMLS:C3813211

The study found that the concentration of prostaglandin E2 (PGE2) was elevated in porous endplates, leading to spinal pain. High-dose treatment with the cyclooxygenase 2 inhibitor, celecoxib, decreased the PGE2 concentration and reduced spinal pain in mice with lumbar spine instability. However, this treatment also impaired bone formation in porous endplates, and spinal pain returned after discontinuing the treatment. Low-dose celecoxib treatment, on the other hand, led to a long-lasting reduction in spinal pain and significantly reduced endplate porosity, which was associated with decreased sensory nerve innervation and spinal pain.


UMLS:C3813211


UMLS:C0915144


UBERON:0001474


UMLS:C4249798