NCBIGene:1236

The study investigates the role of chemokine receptor Ccr7 in osteoarthritis (OA). It was found that CCR7 protein expression is elevated in synovial tissue from OA patients. The study used a murine model of OA and found that deficiency of Ccr7 led to delayed development of joint damage and functional deficits. The study also found that Ccr7 deficiency provided minimal protection from early cartilage degeneration and osteophytosis, and protected from subchondral bone changes. These findings suggest that Ccr7 plays a role in the early development of functional deficits and subchondral bone changes in OA.


NCBIGene:1236

deficiency leads to delayed development of


NCBIGene:1236


NCBIGene:1236

deficiency provides minimal protection from early degeneration of


NCBIGene:1236

deficiency provides minimal protection from


PR:000011194

The paper reviews recent and ongoing trials for pain management in osteoarthritis (OA). The most promising strategy identified is the blockade of nerve growth factor with antibodies, specifically tanuzemab and fasinumab. Other interventions being tested include cytokine inhibition, selective μ, δ or κ opioid receptor agonists, zoledronate, and intra-articular capsaicin. Cryoneurolytic strategies that target peripheral nerves are also being considered, but require further study. The challenge lies in identifying patients who will benefit most from these specific approaches.


UNII:09FZ7Q0PQZ


UNII:WZ1025JPGR


PUBCHEM.COMPOUND:60852


CHEBI:46931


PR:000001808

The study discusses the mechanisms and mediators contributing to the pain associated with Osteoarthritis (OA), a common form of arthritis. The pain in OA is maintained by a strong peripheral nociceptive drive from the affected joint and central sensitization. Mediators such as nerve growth factor, chemokines, cytokines, and inflammatory cells present in the OA joint contribute to sensitization. Structural alterations in joint innervation and nerve damage also occur in OA. The pain in OA is a result of several interrelated pathological processes including joint damage, structural reorganization of joint afferents, low-grade inflammation, neuroplasticity, and nerve damage.


CL:0000863


UBERON:0004770


UMLS:C0161398


NCIT:C174453


NCIT:C156084


PR:000003606

The study investigates the role of a 32-amino-acid aggrecan fragment (32-mer) in causing joint pain in osteoarthritis. The 32-mer fragment is produced through enzymatic degradation of aggrecan by ADAMTS-4 or ADAMTS-5 and further cleavage by MMPs. The 32-mer fragment was found to excite dorsal root ganglion nociceptive neurons and induce the expression of the proalgesic chemokine CCL2. These effects were mediated through TLR2, which is expressed by nociceptive neurons. Intra-articular injection of the 32-mer fragment caused knee hyperalgesia in wild type mice but not in Tlr2-null mice. Blocking the production or action of the 32-mer in transgenic mice prevented the development of knee hyperalgesia in a murine model of osteoarthritis.


PR:000003741


PR:000003742


PR:000010489


PR:000003606

32-amino-acid aggrecan fragment (32-mer)

Dorsal root ganglion nociceptive neurons


PR:000003606


NCBIGene:100042277

The study investigates the nociceptive innervation of normal and osteoarthritic murine knees. The research used C57BL/6 NaV1.8-tdTomato reporter mice and C57BL/6-Pirt-GCaMP3 mice, and protein gene product 9.5 (PGP9.5) immunostaining of C57BL/6 wild type (WT) mice. The study found that nociceptive innervation was most dense in bone marrow cavities, lateral synovium, and at the insertions of the cruciate ligaments in naive 10-week old mice. By age 26 weeks, unoperated knees showed a marked decline in nociceptors in the lateral synovium and cruciate ligament insertions. Late-stage surgically induced osteoarthritis is associated with striking plasticity of joint afferents in the medial compartment of the knee.


NCBIGene:7345


MONDO:0005178


HP:0007021


PR:000001096

The study discusses the role of Toll-like receptors (TLRs) in the progression of Osteoarthritis (OA), a chronic disease affecting synovial joints. TLRs, part of the innate immune system, contribute to pathological changes in OA joint tissues and are involved in initiating and maintaining pain. The study also discusses the effects of specific damage-associated molecular patterns (DAMPs), which act as TLR ligands in vitro, including their direct effects on pain-sensing neurons. Evidence from transgenic mice targeting TLR pathways suggests a balance between pro- and anti-inflammatory signaling pathways activated by OA DAMPs. Clinical evidence also implicates TLRs in OA pathogenesis, including polymorphisms and surrogate markers of disease activity.


PR:000001096


GO:0140426

Damage-associated molecular patterns (DAMPs)


GO:0140426


PR:000001498

The paper discusses the role of innate immunity in osteoarthritis (OA) joint pain. It explains that the activation of neuronal Pattern Recognition Receptors by mediators released in a damaged joint can result in direct excitation of nociceptors, as well as in the production of chemokines and cytokines. Indirect neuro-immune signaling may occur when innate immune cells produce algogenic factors, including chemokines and cytokines, that act on the pain pathway. Immune cells such as macrophages, mast cells, and CD4+ lymphocytes may contribute to nociceptor sensitization and OA pain through the production of algogenic factors that amplify the activation of sensory neurons.


CL:0001082


CHEBI:35480


CL:0000485

Macrophages, Mast cells, CD4+ lymphocytes


MONDO:0008143

The study investigates the role of innate neuro-immune pathways in persistent pain in experimental osteoarthritis (OA) in mice. The researchers performed destabilization of the medial meniscus (DMM) surgery on mice and analyzed gene expression changes in the dorsal root ganglia (DRG) at different stages of OA. They identified three pain phenotypes: "post-surgical pain", "early-stage OA pain", and "persistent OA pain". The study found that genes related to immune cell recruitment and activation were differentially regulated in the persistent OA pain phase. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype. The study also confirmed that Ngf was elevated in the DRG 8 weeks after DMM, and numbers of F4/80+ macrophages were increased 16 weeks after DMM.


NCBIGene:112840934


NCBIGene:4803


CL:0002479


MESH:C520255

The study investigates the mechanisms of acute toxicity produced by paclitaxel treatment on primary sensory neurons under in vitro conditions. The research used primary rat dorsal root ganglion (DRG) culture with paclitaxel and observed an increase of pERK and pp38 at 2 hours, accompanied by an increase in expression and release of C-C chemokine ligand 2 (CCL2). At 48 hours of exposure, the increase in pERK was sustained and the expression of TLR4, MyD88, and IL-6 was also increased. These responses were prevented by coincubation with a TLR4 antagonist (LPS-RS). The study also found evidence of oxidative stress and mitotoxicity at 48 hours of exposure.


MESH:C520255


MESH:D018950


MESH:C520255

Chemotherapy-induced neuropathic pain (CINP)

The study found that blockers of the canonical Wnt signaling pathway, specifically Wnt3a, Wnt10a, and β-Catenin, can prevent and ameliorate chemotherapy-induced neuropathic pain (CINP). This pain is a common side effect of many chemotherapeutic drugs. The study used male Sprague-Dawley rats and male Axin2-LacZ knock-in mice, and induced neuropathic pain through the injection of the chemotherapeutic drug paclitaxel (PAC). The Wnt/β-catenin blockers XAV-939, LGK-974, and iCRT14 were administered and found to prevent the development of CINP. PAC was found to increase Wnt3a and Wnt10a, activate β-catenin in the dorsal root ganglia (DRGs), and increase monocyte chemoattractant protein-1 and interleukin-1β in DRGs.


MESH:C000716507


MESH:C433939


MESH:C099568


PR:000027226

The study investigates the protein distribution of nociceptor markers in the human dorsal root ganglion (DRG) and spinal cord. The peptidergic marker, CGRP, and the non-peptidergic marker, P2X3R, were found to be co-expressed by approximately 33% of human DRG neurons. TrpV1 was expressed in about 60% of human DRG neurons. In the dorsal spinal cord, CGRP, P2X3R, TrpV1, and Nav1.7 proteins stained the entirety of lamina 1-2, with only P2XR3 showing a gradient of expression. The findings suggest that the central projection patterns of nociceptors are different between mice and humans.


PR:000012190


NCBIGene:83810


PR:000002102


PR:000027226


NCBIGene:70086

The study reveals that Cysteinyl leukotrienes (CysLTs), specifically leukotriene C4 (LTC4), and its signaling through the CysLT receptor 2 (CysLT2R) play a significant role in inducing itch. The Cysltr2 transcript is highly expressed in dorsal root ganglia (DRG) neurons linked to itch in mice and CYSLTR2 in human DRG neurons. LTC4-mediated itch differed from pruritogens histamine, compound 48/80, and chloroquine. The study also found that CysLT2R contributes to itch in a model of dermatitis. Therefore, targeting CysLT signaling may be a promising approach to treat inflammatory itch.


CHEBI:62942


NCBIGene:57105


UMLS:C0027792

The paper discusses the changes in peripheral neuronal pathways that cause joint pain in osteoarthritis. It focuses on the plasticity of the nociceptive system in osteoarthritis and how this involves changes in the structural, physiologic, and genetic properties of neurons in pain pathways. The role of the neurotrophin, nerve growth factor, in these pathogenic processes is also discussed. The paper also considers how neuronal pathways are modified by interaction with the degenerating joint tissues they innervate and with the innate immune system.


UBERON:0035017


UMLS:C0027792


GO:0045087

The paper discusses the significant role of the innate immune system in the generation of neuropathic pain, including the pain that accompanies cancer treatment. The innate immune system contributes to cancer treatment pain at various locations including the distal endings of peripheral nerve, in the nerve trunk, in the dorsal root ganglion, and in the spinal dorsal horn.


GO:0045087


CL:0000235

The paper discusses the role of macrophages, a type of immune cell, in the development and persistence of pain in osteoarthritis (OA). Macrophages are adaptable cells that communicate with their environment through various signals such as cytokines, growth factors, and neuropeptides. They are involved in various functions including homeostasis regulation, phagocytosis, and inflammation induction and resolution. The paper suggests that understanding the interaction between macrophages and the nervous system could lead to new therapeutic strategies for chronic pain.


CL:0000235


CL:0000235

may contribute to the initiation and maintenance of


UBERON:0035017

Chronic pain, affecting one in five people, is a significant cause of disability globally. However, treatment is often inadequate due to poor efficacy and tolerability. Nociceptors, which contribute to many chronic pain states, are a promising therapeutic target. Advances in studying human nociceptors have been made, including the use of corneal confocal microscopy, biopsy samples, culture of human nociceptors, transcriptomics, microneurography, and quantitative sensory testing. Genome editing in human induced pluripotent stem cell-derived nociceptors allows for the study of the role of genes in nociceptor function. Differences between human and rodent nociceptors have been found, particularly in ion channel function, expression, and cellular excitability. These advances have highlighted the maladaptive changes in human nociceptors following injury that contribute to chronic pain. Cellular models of human nociceptors have enabled the screening of small molecule and gene therapy approaches on nociceptor function, and in some cases, correlation with clinical outcomes.


CHEBI:25367


NCBIGene:118429

Dorsal root ganglion (DRG) sensory neurons

The study found that dorsal root ganglion (DRG) sensory neurons are rich in ANTXR2, a high-affinity receptor for anthrax toxins. Anthrax toxins, composed of protective antigen (PA), edema factor (EF), and lethal factor (LF), can target these neurons and induce analgesia in mice. The study also found that the analgesic effect depends on ANTXR2 expressed by Nav1.8+ or Advillin+ neurons. The researchers also engineered anthrax toxins to introduce exogenous protein cargoes, including botulinum toxin, into DRG neurons to silence pain.


UBERON:0035017

The study used spatial transcriptomics to analyze the transcriptomes of single dorsal root ganglia (DRG) neurons from eight organ donors. The researchers identified 12 clusters of human sensory neurons, including five C nociceptors, one C low-threshold mechanoreceptors (LTMRs), one Aβ nociceptor, two Aδ, two Aβ, and one proprioceptor subtypes. They also found potential drug targets by examining expression profiles for ion channels, G protein-coupled receptors (GPCRs), and other pharmacological targets. The study also revealed sex differences in human DRG subpopulation transcriptomes, with a significant increase in calcitonin-related polypeptide alpha (CALCA) expression in female pruritogen receptor-enriched nociceptors.


PR:000049983


PR:000030035


PR:000027226

Calcitonin-related polypeptide alpha (CALCA)

Female pruritogen receptor-enriched nociceptors


GO:0098814

The study found that neuropathic pain in rodents and humans can be driven by spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The research showed that pain and SA in both sexes were significantly associated with three functional electrophysiological alterations. These alterations were similar to those reported for nociceptors in rodent chronic pain models. The findings suggest that despite cellular differences between human and rodent DRG neurons, conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain.


UMLS:C0027883


GO:0098814


HP:0001311


UBERON:0035017


MONDO:0005148

The study investigates the molecular mechanisms contributing to diabetic pain in Type 2 diabetes mellitus (T2DM) patients. Dorsal root ganglia (DRG) from patients with painful diabetic peripheral neuropathy (DPN) were analyzed and compared with controls. The transcriptome analyses identified 844 differentially expressed genes. The results showed an increase in inflammation-associated transcripts from macrophages in DPN patients, which may contribute to pain hypersensitivity. Additionally, there was a decrease in neuronally-related genes. These findings provide new insights into the pathology and mechanisms causing neuropathic pain in DPN patients with T2DM.


MONDO:0001583


MESH:D020880


NCIT:C3137

The paper discusses the role of inflammation in causing pain in Osteoarthritis (OA), a leading cause of chronic pain. It highlights that low-level inflammation in OA is a significant factor causing joint damage. The inflammation can occur locally in joint tissues like the synovium, within the sensory nervous system, or systemically due to various factors. The paper also discusses how local inflammation can contribute to mechanical sensitization and structural neuroplasticity of joint nociceptors through pro-inflammatory factors such as nerve growth factor, cytokines, and chemokines. The role of synovitis and neuroimmune interactions are also considered. The paper further explores the role of neuroinflammation in the dorsal root ganglia and dorsal horn and how systemic inflammation associated with obesity may modify OA pain.


NCIT:C3137


PR:000011194


PR:000001808


MONDO:0002400


GO:0150076


MONDO:0011122


MESH:C000656125

The study investigates the metabolism of the phytocannabinoid cannabigerol (CBG) by human cytochrome P450s. The major metabolite formed is cyclo-CBG, which is rapidly produced by selected human cytochrome P450s (CYP2J2, CYP3A4, CYP2D6, CYP2C8, and CYP2C9). In vivo studies with mice confirmed these findings. The study also found that CBG and its oxidized metabolites reduced inflammation in BV2 microglial cells stimulated with LPS.


PR:000013030


MESH:C000656125


HP:0031135

The paper describes the Wakȟáŋyeža (Little Holy One) intervention and evaluation protocol, designed to break cycles of intergenerational trauma, suicide, and substance use among Fort Peck Assiniboine and Sioux parents and their children. The study uses a randomized controlled trial with an embedded single-case experimental design to determine the effectiveness of the intervention on parent-child outcomes and the impact of unique cultural lesson-components. The primary outcomes are parent trauma symptoms and stress, with secondary outcomes including parent depression symptoms, parenting practices, substance use, and child behavior and school attendance. The study aims to provide insights about the potential of a culturally-based intervention to reduce parental distress and thereby reduce risk for children's later substance misuse and suicidality.


HP:0031135


CHEBI:35482

The study analyzed trends in opioid misuse, social support, and suicide attempts among American Indian and Alaska Native (AI/AN) high school students in New Mexico from 2009 to 2019. The prevalence of suicide attempts did not significantly change over time, but was higher among females, those who misused opioids, received low social support, had a mother with less than high school education, had poor academic performance, and non-straight students. Opioid misuse showed a significant decreasing trend from 2009 to 2017, but increased significantly from 2017 to 2019. Students with high maternal education and good school grade performance were less likely to misuse opioids and attempt suicide.


CHEBI:35482

The study investigates the role of social support (SS) in the relationship between opioid misuse and suicide attempts among American Indians and Alaska Natives (AI/AN) high-school students in New Mexico. The study found that high levels of social support significantly reduced the odds of suicide attempts in students who misused opioids. This protective effect was more pronounced in males and in students attending schools in off-reservation and rural communities. The study also found that social support mediated and moderated 23.64% and 41.05% of the association between opioid misuse and suicide attempts, respectively. The mediation effect of social support was lowest for rural, on-reservation schools.


CHEBI:35482

The study aims to address the high prevalence of opioid use disorders (OUDs) among urban American Indian/Alaska Native (AI/AN) emerging adults (ages 18-25) through a randomized controlled trial. The trial will compare the effects of the Traditions and Connections for Urban Native Americans (TACUNA) program, which integrates motivational interviewing, social network visualization, and traditional practices, with a culturally sensitive opioid education workshop. The primary outcomes to be evaluated are the frequency of opioid, alcohol, and cannabis use, and secondary outcomes include social network characteristics and cultural connectedness over a 12-month period.


CHEBI:30879


UNII:69VJ1LPN1S


HP:0000737

The study investigates the relationship between frustration-related lateral prefrontal cortex (LPFC) activation and irritability in children aged 3-7. The researchers found that this relationship is not linear, but rather follows a quadratic model. LPFC activation increased with irritability within the normal range, but decreased with severe irritability, peaking at the 91st percentile. Children who reported mild distress had greater LPFC activation than those reporting no or high distress. This suggests that children with higher irritability but no impairment may have well-developed LPFC support, which is less present in severe irritability.


PR:000050467


MONDO:0005178

The study found a strong association between osteoarthritis (OA), a common cause of chronic pain, and perceived memory loss in a large Appalachian population. The likelihood of reporting frequent memory loss was almost three times higher in participants with OA. This association increased significantly with the frequency of reported joint pain. The influence of sleep and mood disturbance was also examined, and while these factors attenuated the association, they did not eliminate it.


MONDO:0005178


NCIT:C56095


HP:0002360


NCIT:C53834


CHEBI:35482

The study aimed to determine the correlation between the probability of postoperative opioid prescription refills and the amount of opioid prescribed. The study found that the probability of a single postoperative refill did not change with an increase in initial oral morphine equivalents prescribed. Instead, patient factors such as tobacco use, anxiety, mood disorders, alcohol or substance abuse disorders, and arthritis were correlated with the probability of refill. The study suggests that surgeons could prescribe smaller prescriptions without influencing refill requests.


CHEBI:35482


PR:000006269

The study investigates the use of liposome encapsulated KT109, a triazole urea inhibitor of Diacylglycerol lipase-beta (DAGLβ), to target macrophages and inhibit their inflammatory signaling. The researchers found that a small amount of liposomal KT109 was able to inactivate about 80% of DAGLβ in macrophages without affecting other tissues. This targeted delivery resulted in a significant enhancement in antinociceptive potency in a mouse inflammatory pain model, suggesting a potential new anti-inflammatory strategy.


MESH:C108284


PR:000006269


MONDO:0024317

The paper discusses the global issue of persistent pain, which is a leading cause of disability and is often undertreated due to ineffective therapeutics or intolerable side effects. The authors argue that all but the most transient forms of pain should be approached as a disease where a cure can be the goal of all treatment plans. They review recent advances in the neurobiology of pain and discuss barriers to achieving this goal, as well as the development of new therapeutic strategies. They also highlight innovations that are creating new opportunities to treat and even reverse persistent pain, some of which are in late-phase clinical trials.


MONDO:0004456

The study investigates the neurobiology of attentional bias in individuals with cocaine use disorder (CocUD) using dynamic causal modeling (DCM) based on functional magnetic resonance imaging (fMRI) data. The results showed that cocaine-word cues significantly increased the effective connectivity between the right anterior cingulate cortex (ACC) and the right hippocampus. This increased connectivity was associated with greater reaction time to cocaine-word cues. The researchers suggest that this circuit could be a potential target for therapeutics in CocUD patients.


MONDO:0004456


PUBCHEM.COMPOUND:446220


UBERON:0009835


HP:0012532

The paper discusses the role of persistent pain, which affects a significant portion of the global population. Persistent pain is primarily caused by the sensitization of nociceptive neurons, which involves new gene expression to support the necessary biochemical and structural changes for amplified pain signaling. The paper emphasizes that while transcription-dependent changes in gene expression are significant, the regulation of mRNA translation is crucial in controlling the cellular proteome and the development and maintenance of persistent pain. The paper also highlights recent advances in the translational regulation of gene expression in nociceptive circuits, suggesting potential targets for the development of new pain therapeutics.


UBERON:0035017


GO:0010468


GO:0016556


MESH:C523259

The study investigates the effects of treating pregnant women with opioid use disorders using buprenorphine + naloxone in Appalachia. The results showed that all neonatal birth outcome parameters were within normal ranges, although on the lower side of normal for gestational age and birth weight. Only 19% of neonates required morphine for Neonatal Abstinence Syndrome (NAS). The findings suggest that the use of buprenorphine + naloxone is relatively safe during pregnancy.


MESH:C520255

The study investigates the use of monoacylglycerol lipase (MAGL) inhibitors, specifically JZL184 and MJN110, in reversing paclitaxel-induced mechanical allodynia (a type of neuropathic pain) in mice. The inhibitors were found to dose-dependently reverse allodynia, with the antiallodynic effects requiring both cannabinoid receptors, CB1 and CB2. MJN110 also reduced the expression of monocyte chemoattractant protein-1 (MCP-1, CCL2) and phospho-p38 MAPK in dorsal root ganglia and MCP-1 in the spinal dorsal horn. Repeated administration of a threshold dose of JZL184 completely reversed paclitaxel-induced allodynia. Importantly, the inhibitors did not interfere with the antiproliferative and apoptotic effects of paclitaxel in non-small cell lung cancer cells.


MESH:C587862


MESH:C476980


MONDO:0011382

Sickle cell disease (SCD) is a genetic disorder that causes recurrent acute pain and chronic persistent pain. The pain is currently treated with opioids, but this approach has limitations due to adverse effects. The paper discusses the cellular and molecular mechanisms of sickle cell pain, including mast cell activation, neurogenic inflammation, peripheral nociceptor sensitization, maladaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. The authors suggest potential preventive/therapeutic targets and novel pharmacologic and/or integrative approaches to alleviate sickle cell pain.


CHEBI:35482


CL:0000097


UBERON:0014777


UMLS:C0027792


MESH:D053610

The study evaluated the effectiveness of a multi-modal, interprofessional educational approach in changing opiate prescribing practices among healthcare professionals. The educational activities included webcasts, roundtable events, and conference presentations. Over 1,000 participants, including nurses, nurse practitioners, and physicians, accessed the activities. The study found that the majority of the participants intended to make changes in their chronic pain patient management practices after the events. There were significant changes in knowledge for both live event and webcast participants, and participants were more confident post-activity than their control group peers.


MESH:C560330

The paper discusses the pharmacogenetics of Opioid Use Disorder (OUD) treatment. It highlights the role of genetic variation in the effectiveness of OUD medications such as methadone and buprenorphine. The genetic variation can affect the pharmacokinetic or pharmacodynamic effects on OUD medications, or it can influence the rate of negative side effects and adverse events. The paper reviews the existing literature on the pharmacogenetics of OUD treatment, focusing on medication metabolism, treatment outcomes, and adverse events.


GO:0020033


PR:000001662

The study investigates the role of Protease activated receptor 2 (PAR2) in causing migraine-like pain behaviors in mice. The research used selective pharmacological agents and knockout mice to study the effect of a specific PAR2 agonist, 2at-LIGRL-NH2, on primary trigeminal and dural cell cultures. The study found that 2at-LIGRL-NH2 evoked Ca2+ signaling in mouse trigeminal neurons, dural fibroblasts, and meningeal afferents. Dural application of 2at-LIGRL-NH2 or 48-80, a mast cell degranulator, caused dose-dependent grimace behavior and mechanical allodynia that were attenuated by either local or systemic application of C391, a selective PAR2 antagonist, as well as in PAR2-/- mice. The study suggests that PAR2 may link resident immune cells to meningeal nociceptor activation, driving migraine-like pain and implicating PAR2 as a therapeutic target for migraine in humans.


MESH:C000595466


CHEBI:75295


MESH:C425528

Sphingosine-1-phosphate (S1P) receptors (S1PR)

The study investigates the effects of the prodrug FTY720, an agonist for sphingosine-1-phosphate (S1P) receptors (S1PR), as a potential pain therapeutic. The research found that FTY720 produced dose-dependent antinociception and antiallodynia in both acute thermal and chronic neuropathic pain models in mice. However, repeated administration of FTY720 led to tolerance in the acute thermal model but not in the chronic neuropathic pain model. This suggests a differential mechanism of FTY720 action between these models. The study also found that repeated FTY720 administration led to desensitized S1PR1 signaling throughout the central nervous system.


MESH:C425528


MESH:C425528

leads to desensitized S1PR1 signaling in


MONDO:0008241

The study found that new persistent opioid use is a common postoperative complication, with 6% of previously opioid-naïve patients continuing to fill opioid prescriptions 3-6 months after surgery. The study identified that surgeons provide the majority of opioid prescriptions during the first 3 months after surgery. However, 9 to 12 months after surgery, the majority of opioid prescriptions were provided by primary care physicians. The study suggests that enhanced care coordination between surgeons and primary care physicians could allow earlier identification of patients at risk for new persistent opioid use to prevent misuse and dependence.


NCBIGene:4988

Opioid use disorder (OUD) has a significant genetic component, with the risk of developing the disorder being influenced by certain genetic variants. These variants have been identified through candidate gene studies and genome-wide association studies (GWAS). The most studied candidate genes include the mu-opioid receptor (OPRM1), the delta-opioid receptor (OPRD1), the dopamine D2 receptor (DRD2), and brain-derived neurotrophic factor (BDNF). Variants in these genes have been associated with small, but reproducible, effects on OUD risk. GWAS have also identified potential associations with variants in KCNG2, KCNC1, CNIH3, APBB2, and RGMA. However, these genetic associations only explain a small portion of OUD risk. Future studies will need to incorporate rare variants, epigenetics, and gene × environment interactions to better explain the observed heritability.


NCBIGene:18386


NCBIGene:1813


NCBIGene:12064

brain-derived neurotrophic factor (BDNF)


NCBIGene:26251


NCBIGene:3746


NCBIGene:72978


NCBIGene:323


NCBIGene:244058


MESH:C540131

The study aimed to compare the availability of kappa opioid receptors (KOR) in alcohol-dependent individuals and healthy controls. Using PET scans with [11C]LY2795050, a selective kappa antagonist tracer, the researchers found that alcohol-dependent individuals had significantly lower KOR availability in the amygdala and pallidum. The study also found no significant change in KOR availability with age.


PR:000001590


CHEBI:35482

The study aimed to reduce opioid prescribing after breast and melanoma procedures through an intervention focused on education and prescribing guidelines. The intervention led to a significant decrease in the mean quantity of opioid prescribed for mastectomy or wide local excision for melanoma by 37%, and for lumpectomy or breast biopsy by 42%. The frequency of opioid prescription refills did not significantly change, suggesting that the intervention did not increase the need for refills. This indicates that further reductions in opioid prescribing may be possible with similar interventions.


CHEBI:35482


MESH:C495231


CHEBI:35482

The study investigates the incidence of Neonatal abstinence syndrome (NAS) in West Virginia (WV) using a real-time statewide surveillance system, Project WATCH. NAS is a condition affecting newborns after discontinuation of prenatal drug exposure, primarily opioids. The study examined all births in WV from October to December 2017. The annual incidence rate of NAS was found to be 51.3 per 1000 live births per year for all births and 50.6 per 1000 live births per year for WV residents only. The study suggests the need to develop effective care systems for mother-infant dyads affected by substance use, particularly targeting pregnant women in rural communities.


NCIT:C124295


CHEBI:35482

The study analyzed the incidence and factors associated with new persistent opioid use after lung resection in opioid-naïve cancer patients. The study found that 14% of opioid-naïve patients continued to fill opioid prescriptions following lung resection. The independent risk factors for persistent opioid usage were identified as age less than or equal to 64 years, male sex, postoperative length of stay, thoracotomy, and adjuvant therapy. The greatest risk factors were adjuvant therapy and thoracotomy.


MONDO:0024317

The study investigates the feasibility and acceptability of a mobile phone app, MyBehaviorCBP, that uses machine learning to generate personalized physical activity recommendations for individuals with chronic back pain. The app's recommendations are based on routine behaviors, making them more likely to be followed. A 5-week pilot study showed that 90% of participants were positive about trying the app's recommendations, and found them easier to adopt compared to generic recommendations. The app's recommendations also led to an increase in physical activity, with participants walking approximately 5 minutes more per day.


CHEBI:35482

The study found that the quantity of opioids prescribed after surgery was significantly higher than the patient-reported opioid consumption. The quantity of opioid prescribed was the strongest factor associated with patient-reported opioid consumption. Other significant risk factors included patient-reported pain in the week after surgery, history of tobacco use, American Society of Anesthesiologists class, age, procedure type, and inpatient surgery status. The study suggests that using patient-reported opioid consumption to develop better prescribing practices is an important step in combating the opioid epidemic.


PUBCHEM.COMPOUND:90477108

The study analyzed drug-related deaths in West Virginia, United States from 2005 to 2017, focusing on the involvement of fentanyl and fentanyl analogs (FAs). The study found that while prescription opioid-related deaths decreased by 75% from 2005-14 to 2015-17, deaths involving fentanyl increased by 122% in the same period. Ten FAs were identified after 2015. Substances such as alprazolam and ethanol were frequently identified, and fentanyl, heroin, and cocaine replaced oxycodone, diazepam, and hydrocodone in the top five substances identified beginning in 2015. The study concludes that fentanyl, FAs, and other illicit drugs pose a serious health threat despite the decrease in prescription opioid-related deaths.


CHEBI:84144


CHEBI:35482

The study investigates the variation in long-term opioid use in osteoarthritis patients based on geography and health care access. The study found that the percentage of osteoarthritis patients taking long-term opioids varied widely across states, with the highest in Alabama and the lowest in Minnesota. Access to primary care providers was only slightly associated with rates of long-term opioid use, while access to rheumatologists was not associated with long-term opioid use. The variation in long-term opioid use was not fully explained by differences in access to health care providers, varying case-mix, or state-level policies.


PUBCHEM.COMPOUND:3682292


PUBCHEM.COMPOUND:76956004


NCBIGene:4330


CHEBI:35482

The study found that 8.3% of opioid-naïve patients developed prolonged opioid use after shoulder arthroscopy. Factors associated with a higher risk of prolonged opioid use included a high total opioid dose during the perioperative period, suicide and self-harm disorder, history of alcohol dependence or abuse, mood disorder, opioid prescription filled in the 30 days before surgery, female sex, anxiety disorder, and a history of a pain diagnosis. The risk of prolonged opioid use was higher among women and those with greater opioid use in the early postoperative period, mental health conditions, substance dependence and abuse, and preexisting pain disorders.


PR:000027226

The study found that the application of calcitonin gene-related peptide (CGRP) to the rat dura mater produces cutaneous periorbital hypersensitivity, but only in female rats. Males showed no response to doses of CGRP ranging from 1 pg to 3.8 μg. In females, CGRP caused priming to a pH 7.0 solution after recovery from the initial CGRP-induced allodynia. The application of interleukin-6 caused acute responses in both sexes but only caused priming to subthreshold dural CGRP in females. Similarly, the application of BDNF caused acute hypersensitivity responses in both sexes but only priming to subthreshold dural CGRP in females. The study also found that females were primed to a subthreshold dose of the NO-donor sodium nitroprusside following dural CGRP. These findings suggest that CGRP-induced headache-like behavioral responses are female-specific and that dural CGRP signaling plays a role in the pathophysiology of migraine.


PR:000027226


PR:000001393


NCBIGene:627


MESH:C003320

primed to in females after CGRP application


MESH:C488329

The study investigated the feasibility of an opioid-sparing pain management strategy after surgical procedures. Patients were advised to use acetaminophen and ibuprofen, with a small "rescue" opioid prescription for breakthrough pain. The results showed that 52% of patients used no opioids after procedures, and 91% agreed that their pain was manageable. Patients who used opioids were younger, reported higher pain scores, received larger rescue prescriptions, and were less likely to agree that their pain was manageable. The study concluded that an opioid-sparing pathway is effective and acceptable for major reduction and even elimination of opioids after minor surgical procedures.


MESH:C521966


CHEBI:35482

The study examined the patterns of prescription opioid use before total joint replacement (TJR) in Medicare enrollees aged 65 years and above. It was found that 60.2% of patients had used opioids, with 12.4% using them continuously over a 12-month period before surgery. Factors associated with continuous opioid use included African American race, history of drug abuse, and back pain. The study suggests further research is needed to determine the risks of preoperative opioid use in TJR patients and to optimize pain management.


CHEBI:35482


CHEBI:35482

The paper discusses the impact of opioids on the fetal brain, which has been overlooked in the debate between medication-assisted treatment and medically supervised withdrawal for pregnant women with opioid use disorder. Studies have shown that opioids negatively affect the human brain, particularly the developing oligodendrocyte and processes of myelinization, brain connectivity, and the size of multiple brain regions. The long-term effects of these changes in the fetal brain are unclear, but potential lasting injury has been suggested. The authors propose a new paradigm of care that includes both medication-assisted treatment and medically supervised opioid withdrawal, along with mental health and social services support.


CHEBI:35482

The study analyzed Medicare Part D claims of patients over 65 years old who underwent surgery between 2009 and 2015. It was found that 9.8% of these patients, who had not filled an opioid prescription before their surgery, developed new persistent opioid use postoperatively. Risk factors for this included major surgery, comorbid conditions, mood disorders, suicide or self-harm, substance abuse disorders, preoperative opioid prescription fill, higher amounts of opioids filled, black race, and Medicaid eligibility.


MESH:C502494

The study compared the effects of naltrexone (NTX) and buprenorphine (BUP) on pregnant women with opioid use disorder (OUD) and their infants. The results showed that none of the women on NTX had documented opioid misuse compared to 23% of the women on BUP. Furthermore, no infants in the NTX group had a neonatal abstinence syndrome (NAS) diagnosis compared to 92% in the BUP group. NTX-exposed infants also had a shorter hospital stay. The study concluded that maintaining women on NTX during pregnancy was associated with favorable outcomes.


MESH:C502495


MESH:C502494


CHEBI:35482

The study aimed to identify patient characteristics linked to postoperative outpatient opioid use and the frequency of opioid overprescribing. The study included opioid-naïve patients undergoing major surgeries such as hysterectomy, thoracic surgery, and total knee and hip arthroplasty. The study found that younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. The study suggests that future research should focus on the use of non-opioid medications and behavioral therapies for these higher-risk patients.


MONDO:0001225

The study investigates the relationship between brain region interactions and opioid use disorder (OUD). Using functional magnetic resonance imaging (fMRI) data from 27 participants with OUD (some of whom also had cocaine use disorder), the researchers analyzed effective connectivity during an opioid-word Stroop task. They found that the effective connectivity from the left anterior cingulate cortex (ACC) to the right hippocampus showed the most significant change, which was positively correlated with attentional bias towards opioid-related cues. This finding was consistent across both OUD and cocaine use disorder.


MONDO:0001225


CHEBI:35482

The study reviews the development and implementation of evidence-based guidelines for postoperative opioid prescribing, a significant contributor to the current opioid epidemic. The research involved a review of thirty studies and institutional experiences, focusing on patient-reported outcomes, key stakeholders, and continual assessment. The implementation of these guidelines, based on a learning health system model, resulted in a 37% to 63% reduction in opioid prescribing without increasing requests for refills or patient-reported pain scores, indicating that it can be effectively used in diverse practice environments without adversely affecting patient outcomes.


GO:0004985

Chronic Temporomandibular Disorder (TMD) pain

The paper investigates the relationship between µ-Opioid activity and chronic Temporomandibular Disorder (TMD) pain, and how this relationship is influenced by Catechol-O-methyltransferase (COMT) polymorphism. The main finding is that there is an association between µ-Opioid activity in chronic TMD pain and COMT polymorphism.


GO:0004985


MONDO:0021895

Chronic Temporomandibular Disorder (TMD) pain


CHEBI:35482

The study evaluated the effects of shared decision making using a decision aid for opioid prescribing after hysterectomy. The decision aid was used to educate patients about postoperative pain management and the number of opioid tablets recommended per prescription. The results showed that patients who participated in the decision aid were discharged with significantly fewer oral morphine equivalents than patients who underwent hysterectomy before the implementation of the decision aid. There was no significant change in the number of requested refills. The decision aid resulted in a significant decrease in opioid prescribing without compromising patient satisfaction or postoperative pain management.


UBERON:0000955

The paper discusses the use of positron emission tomography (PET) in studying the function of the human brain, particularly in relation to pain and migraine. The study highlights the role of PET in understanding the brain's response to different stimuli such as pain, reward, and the administration of active or placebo interventions. The paper also emphasizes the importance of PET in exploring the dynamic interaction between behavior and genetic factors and between different pain modulatory systems. The study confirms the involvement of brain structures in pain processing and modulation and helps elucidate the neural mechanisms that underlie healthy and pathological pain regulation.


UBERON:0000955


GO:0007610


PR:000001612

The study investigates the ethnic differences in pain perception, focusing on the role of µ-opioid receptor (MOR) function. The research involved 27 non-Hispanic black (NHB) and 27 non-Hispanic white participants, who underwent PET imaging and pain rating collection. The results showed significantly greater [C]-Carfentanil BPND (a measure of MOR density) among NHB participants in several brain regions. However, there were no significant main effects of condition or ethnicity × condition interaction effects across models. The study suggests that NHB individuals might have generally greater unoccupied MOR density than non-Hispanic white peers, which could be a physiological difference underlying ethnicity-related pain disparities.


UBERON:0001017

The paper discusses new findings in the pathophysiology of migraines, a common and disabling disorder. The study highlights the role of the central and peripheral nervous systems in migraine attacks. It also discusses the role of the vasculature, calcitonin gene-related peptide (CGRP), and mechanisms within the cortex and meninges in contributing to attacks. The paper also discusses new therapeutic targets, including acid-sensing ion channels (ASICs) and the delta-opioid receptor (DOR), which show promise in preclinical studies.


UBERON:0000010


UBERON:0002049


PR:000027226


UBERON:0001851


UBERON:0003548


PR:000044662


PR:000001579


CHEBI:35482

The study examined the impact of opioid prescribing duration limits on postoperative opioid prescribing in Massachusetts and Connecticut. The results showed that the implementation of these limits in Massachusetts was associated with a decrease in prescription size, days supplied, and the proportion of prescriptions exceeding a 7-day supply. However, the same was not observed in Connecticut. The study suggests that efforts to reduce opioid prescribing should include surgeon education and evidence-based prescribing recommendations.


MONDO:0001225

Persistent or increased post-transplant opioid use

The study examined opioid use in patients before and after liver transplantation. It was found that 45% of patients filled at least one opioid prescription in the year before transplant, and 61% filled an opioid prescription 0-2 months after discharge. Among patients who were opioid-naive before the transplant, 4% developed chronic use post-transplant. Pretransplant opioid use and hepatobiliary malignancy were identified as factors associated with the risk of persistent or increased post-transplant opioid use.


MONDO:0002514


PUBCHEM.COMPOUND:29746

The study aimed to validate the pain measurements of a neuroscience-based 3D body pain mobile app called GeoPain in patients with temporomandibular disorder (TMD). The results showed that GeoPain measures had a high internal consistency and were strongly associated with TMD pain. The GeoPain measures also demonstrated an association between chronicity and TMD pain in locations spread away from the most commonly reported area or pain epicenter. The long-term reliability was consistently high for the pain area and intensity number summation (PAINS) with lag autocorrelations averaging between 0.7 and 0.8. The combination of higher reliability for PAINS and its objectivity, displayed by the lack of association with PANAS as compared with VAS, indicated that PAINS has better sensitivity and reliability for measuring treatment effect over time for sensory-discriminative pain.


HP:0012531

has better sensitivity and reliability for measuring


PUBCHEM.COMPOUND:29746


HP:0012531


CHEBI:46931

The study investigated ethnic differences in pain responses to capsaicin, a common experimental pain stimulus, among non-Hispanic black (NHB) and non-Hispanic white (NHW) adults. The researchers used infrared thermography to measure capsaicin-induced neurogenic flare and secondary hyperalgesia. The results showed that while experimenters rated a significantly wider area of capsaicin-related neurogenic flare among NHW compared to NHB participants, thermography results showed no differences between the groups. Furthermore, NHB individuals reported greater average pain during the capsaicin procedures compared to NHW individuals, but the groups did not differ in secondary hyperalgesia. The study concluded that infrared thermography could be used over subjective experimenter report when measuring neurogenic inflammation in diverse samples, but it should not be used as a diagnostic tool for pain.


CHEBI:46931


MESH:C465865

The study investigates the effects of pimavanserin and lorcaserin, two FDA-approved drugs, on cocaine intake and cocaine-seeking behavior in male rats. The results show that acute administration of lorcaserin reduced cocaine intake, but pimavanserin did not have this effect. However, repeated administration of both drugs during forced abstinence from cocaine self-administration reduced cocaine-seeking behavior. This suggests that repeated treatment with pimavanserin and lorcaserin could potentially help to manage relapse-like behaviors in cocaine use disorder (CUD).


MESH:C465865


MESH:C000708178


CHEBI:35482

The study found that preoperative opioid use is associated with higher rates of readmissions following surgery. This includes opioid-related, pain-related, and respiratory-related readmissions. The risk of readmission increases with the level of preoperative opioid exposure. The study suggests the importance of screening patients for preoperative opioid use and developing risk mitigation strategies.


MONDO:0024317

The study examined the effects of patient race and socioeconomic status (SES) on providers' decisions regarding chronic pain care. It was found that Black and low SES patients received less adequate pain care compared to White and high SES patients. The study also found that providers' implicit and explicit attitudes about race and SES influenced their decisions to some extent. For instance, Black and low SES patients were more likely to be recommended opioids and opioid contracts.


MONDO:0024317

The study is a randomized trial that aims to evaluate the mechanisms of three chronic pain treatments: cognitive therapy (CT), mindfulness meditation (MM), and activation skills (AS). The study will involve 300 individuals with chronic pain, primarily or secondarily associated with low back pain. The treatments' effectiveness will be assessed through changes in cognitive content, cognitive process, and activity level. The primary outcome will be measured by the PROMIS 5-item Pain Interference scale. The study will also examine relapse mechanisms post-treatment.


PR:000001662

The study investigates the cellular basis of pain evoked by Protease-activated receptor 2 (PAR2). The researchers developed a PAR2-conditional knockout mouse and deleted PAR2 in all sensory neurons. The results showed that PAR2 agonist-evoked mechanical hyperalgesia and facial grimacing, but not thermal hyperalgesia, are dependent on PAR2 expression in sensory neurons that project to the hind paw in both male and female mice. F2rl1 mRNA is expressed in a small population of sensory neurons that coexpress the Nppb and IL31ra genes. This cell population has been implicated in itch, but the study shows that PAR2 activation in these cells causes clear pain-related behaviors from the skin.


PR:000001662


NCBIGene:14063


NCBIGene:18158


NCBIGene:133396


CHEBI:30879

The study quantifies the influence of alcohol, polysubstance use, and other factors on opioid concentrations in drug-related deaths in West Virginia, United States. The study found that alcohol concentrations of 0.08% or above were associated with significant reductions in blood concentrations of fentanyl, hydrocodone, and methadone. Lower predicted concentrations of all opioids studied were associated with multiple opioid vs. single opioid presence. Benzodiazepine presence was associated with small, non-statistically significant changes in opioid concentrations, while stimulant presence was associated with statistically significant reductions in hydrocodone and oxycodone concentrations. Co-ingestion of alcohol, multiple opioids or stimulants were associated with significantly decreased predicted concentrations of commonly identified opioids in drug deaths.


CHEBI:35482


CHEBI:22720


CHEBI:35480


CHEBI:30879

reduces concentration of when co-ingested


NCIT:C164341

The study evaluated the impact of surgeon experience on opioid prescribing after surgery. It was found that the amount of opioids prescribed was highest for patients whose surgeons were early in their practice (0-7 years). Other factors such as surgeon credentials, type of surgery, and geographic region also influenced the size of opioid prescriptions postoperatively.


CHEBI:35482

The study found that patients with chronic opioid use who had a consistent usual prescriber (UP) prior to surgery and returned to that UP within 30 days post-surgery were less likely to experience high-risk opioid prescribing events. High-risk prescribing events include multiple prescribers, overlapping opioid and/or benzodiazepine prescriptions, new long-acting opioid prescriptions, or new dose escalations to over 100mg OME. Patients without a UP prior to surgery were more likely to be exposed to high-risk opioid prescribing.


MONDO:0011382

The study investigated the effect of inhaled cannabis on chronic pain in adults with Sickle Cell Disease (SCD). The randomized clinical trial involved participants inhaling vaporized cannabis (4.4% Δ-9-tetrahydrocannabinol to 4.9% cannabidiol) or a placebo three times daily for five days. The results showed that, compared to the placebo, vaporized cannabis did not significantly reduce pain and associated symptoms, except for interference in mood, in patients with SCD with chronic pain.


MONDO:0001225

The study found that patients in treatment for opioid use disorder (OUD) in rural Appalachian areas have high rates of adverse childhood experiences (ACE), with females reporting significantly more experiences than males. Specifically, female patients were more likely to have experienced sexual abuse and forced sex before age 18. These high rates of childhood adversities, particularly among females, may partially explain despair in rural Appalachian areas. The study suggests that OUD treatment programs should conduct clinical assessments of trauma and integrate trauma-informed care into drug treatment, especially for female patients residing in rural Appalachia.


UBERON:0003100


CHEBI:35482

This pilot study investigated the impact of prenatal opioid exposure on the developing brain networks of infants. The study used resting state functional MRI (rs-fMRI) to evaluate alterations in amygdalar functional connectivity in 10 infants with prenatal opioid exposure and 12 infants without prenatal drug exposure. The results showed significant differences in the connectivity of the amygdala seed regions to several cortical regions, including the medial prefrontal cortex, in infants who had prenatal opioid exposure compared to opioid naïve infants. This suggests that maternal opioid exposure may have a potential role in altering infants' amygdala function.


CHEBI:35482

The study found that 1.5% of patients developed new persistent opioid use after undergoing inguinal hernia repair. The most significant risk factor for this was filling an opioid prescription in the 30 days before surgery. Other risk factors included receiving a larger opioid prescription, having more comorbidities, having a major postoperative complication, and certain mental health disorders and pain disorders.


MESH:D053610

The study investigates the relationship between neonatal abstinence syndrome (NAS) and health insurance status in a rural population in West Virginia, USA. NAS is defined as neonatal withdrawal from substances, including opiates. The study found that Medicaid covered more than half of all infants' births in the state, and the incidence of NAS was significantly higher in the Medicaid-insured group compared to the privately insured group. The study highlights the disparity in NAS by health insurance status and its burden on the state's Medicaid program.


HP:0030833

The study aimed to predict the response of patients with low back pain to spinal manipulative therapy (SMT) using a restricted, non-pragmatic methodology, established variables of responder status, and newly developed physical measures. The study found that response to treatment was predicted by a model containing eight variables: height, gender, neck or upper back pain, pain frequency in the past 6 months, the STarT Back Tool, patients' expectations about medication and strengthening exercises, and extension status. The model had a sensitivity of 72.2%, specificity of 84.2%, a positive likelihood ratio of 4.6, a negative likelihood ratio of 0.3, and area under ROC curve, 0.79.


UBERON:2000106


PUBCHEM.COMPOUND:90477108

The study aimed to determine the prevalence of fentanyl (a synthetic opioid) in specimens submitted for definitive opioid testing in West Virginia, an area with high fentanyl-related deaths. The study found that fentanyl positivity was 11% in the first quarter of 2020, with over 60% of these findings being unexpected. The data prompted the addition of fentanyl to routine drug screen panels in the laboratory and a 10% random fentanyl screening rate in the Behavioral Medicine opioid use disorder clinics.


CHEBI:35482

The study investigates the effectiveness of percutaneous peripheral nerve stimulation (PNS) as a nonpharmacologic alternative for the treatment of postoperative pain. The researchers hypothesize that PNS will reduce surgical pain and opioid consumption during the initial 7 days after surgery compared to usual analgesia. The study is a multicenter pragmatic effectiveness trial where participants undergoing painful orthopedic surgical procedures are randomized to receive either electrical stimulation or sham. The results of this study could potentially revolutionize postoperative analgesia, providing potent analgesia with fewer risks and no systemic side effects or potential for abuse, addiction, and overdose, unlike opioids.


MONDO:0024317

The study is a pragmatic superiority trial that aims to determine if a remotely delivered cognitive behavioral therapy for chronic pain (CBT-CP) outperforms in-person and other synchronous forms of CBT-CP for veterans with chronic musculoskeletal pain. The trial compares an asynchronous form of CBT-CP that uses interactive voice response (IVR) with synchronous CBT-CP delivered by a Department of Veterans Affairs (VA) clinician. The primary outcome is pain interference after treatment. Secondary outcomes include pain intensity, depression symptom severity, sleep, self-efficacy, and global impression of change. The study also discusses the implications of COVID-19 on treatment provision and trial outcomes.


MONDO:0024317


MESH:C495231

The study retrospectively analyzed universal umbilical cord tissue drug analysis (UCTDA) data to report the incidence of in utero drug exposure in West Virginia. The study found that the overall positivity for drugs in UCTDA specimens decreased from 25% to 20% between two epochs. However, there was an increase in positivity for hydrocodone, oxycodone, amphetamines, and cocaine, while fentanyl and morphine positivity decreased. Buprenorphine detection increased. Most positive specimens had one drug present, but some had 2 to 6 discrete drugs.


CHEBI:35338


MESH:D016578


PUBCHEM.COMPOUND:90477108


MESH:C523259


MESH:C560330


MONDO:0001225

The study found a high prevalence of co-occurring substance use in individuals with opioid use disorder (OUD) in West Virginia. The most common co-occurring substances were benzodiazepines, cannabis, cocaine, and amphetamine. Individuals with co-occurring substance use were younger and had a higher prevalence of hepatitis C virus (HCV) compared to those who used opioids alone. The study also found an increase in the rate of co-occurring amphetamine and opioid use over a 10-year period.


MONDO:0001225


MONDO:0021698

The study aimed to identify the organizational capacity and readiness to provide medication for Alcohol Use Disorders (AUD) in outpatient public mental health clinics. The study was conducted in eight publicly funded outpatient mental health clinics operated by the Los Angeles County Department of Mental Health. The findings revealed significant organizational capacity and behavioral readiness constraints to providing medication treatment for AUD. The constraints included large caseloads, staffing configurations, time constraints, and a lack of protocols and workflow procedures.


CHEBI:35482

The study aimed to identify any differences in fetal brain development and structure in fetuses exposed to opioids in utero, compared to those not exposed. The study found a significant difference in the anteroposterior diameter of the fetal cerebellar vermis in opioid-exposed fetuses. However, no significant differences were found in other brain dimensions or in brain maturation and structure. The study also found no major brain structural abnormalities in opioid-exposed fetuses.


CHEBI:35482

does not significantly affect maturation or structure of


NCBITaxon:2426

The study found a new fatty acid, turneroic acid, and two previously known oxylipins from the culture broth of the shipworm endosymbiont Teredinibacter turnerae. These compounds were found to inhibit bacterial biofilm formation in Staphylococcus epidermidis. The study also highlighted the importance of the epoxide moiety for selective and potent biofilm inhibition.


MESH:C432163


CHEBI:61121


CHEBI:32955


NCBIGene:14064

The study investigates the role of Protease Activated Receptor Type 3 (PAR3) in nociception (pain perception). The researchers found that PAR3 is widely expressed in dorsal root ganglion (DRG) neurons and co-expressed with other PARs in various DRG neuron subpopulations. They developed a lipid tethered PAR3 agonist, C660, that selectively activates PAR3, inducing mechanical hypersensitivity and facial grimacing in wild type (WT) mice but not in PAR3-/- mice. The study also found a loss of hyperalgesic priming in response to IL-6, carrageenan, and a PAR2 agonist in PAR3-/- mice, suggesting that PAR3 contributes to long-lasting nociceptor plasticity in some contexts. The nociceptive effects of PAR1 agonists were potentiated in the absence of PAR3, suggesting a complex role of PAR3 in the physiology and plasticity of nociceptors.


MESH:C077099


NCBIGene:14064


CHEBI:87635


MESH:D012270

Calcitonin gene-related peptide (CGRP/Calca)

The study investigates the role of protein synthesis in regions of RNA annotated as noncoding in the context of pain-associated behavior. The researchers found evidence of widespread translation in noncoding transcripts and regulatory regions of mRNAs. They identified an increase in ribosome occupancy in the 5' untranslated regions of the calcitonin gene-related peptide (CGRP/Calca). They confirmed the existence of an upstream open reading frame (uORF) and found that a peptide corresponding to the CGRP-encoded uORF resulted in pain-associated behavioral responses in mice and nociceptor sensitization in vitro. This effect was blocked by an inhibitor of heterotrimeric G protein signaling, suggesting that the uORF-encoded peptide promotes pain sensitization through GPCR signaling.


CHEBI:35482

The study developed a model to predict persistent high-dose opioid use in patients who underwent total knee replacement (TKR). The model used 83 preoperative patient characteristics and identified four distinct opioid use patterns. The model showed high discrimination in predicting persistent high-dose opioid use. A reduced model with 10 predictors performed equally well. The study found that 10.6% of older patients became persistent high-dose opioid users after TKR.


MONDO:0043510

The paper discusses the formation of the Military Treatment Facility Engagement Committee (MTFEC) to support pragmatic clinical trials (PCTs) in the Military Health System. The MTFEC was created to address the high prevalence of chronic pain among military service members and veterans, often related to traumatic experiences such as traumatic brain injury or limb loss. The MTFEC is part of a larger initiative by the National Institutes of Health (NIH), Department of Defense (DOD), and Department of Veterans Affairs (VA) Pain Management Collaboratory (PMC) to focus on nonpharmacological approaches for pain management. The MTFEC provides expertise and leadership in executing research studies within the DOD health care system, identifying potential barriers and challenges to study implementation.


HP:0009826


PUBCHEM.COMPOUND:1832219

The study examined the impact of Prescription Drug Monitoring Program (PDMP) policy reform on prescribing rates for human and veterinary providers in West Virginia from 2008 to 2020. The data showed that the prescribing rates for opioids increased significantly for veterinarians, while it decreased for human providers, especially after the implementation of the Opioid Reduction Act in 2018.


MESH:C495231

The study tested the hypothesis that patients prescribed hydrocodone consume a similar number of tablets as those prescribed oxycodone after surgery. The results showed that patients prescribed hydrocodone consumed more tablets than those prescribed oxycodone, but this difference was not clinically significant and did not result in differences in satisfaction, pain, or refills. Therefore, perioperative opioid prescribing guidelines may recommend the same number of 5 mg oxycodone and hydrocodone tablets without sacrificing patient-reported outcomes.


MONDO:0021895

has reduced levels in dlPFC, medial dorsal thalamus, M1, S1

The study investigates the relationship between brain signal variability and chronic pain in temporomandibular disorder (TMD) patients. The research found that TMD patients had reduced blood-oxygen-level-dependent signal variability (BOLDSV) in the dorsolateral prefrontal cortex (dlPFC), medial dorsal thalamus, primary motor cortex (M1), and primary somatosensory cortex (S1), and increased BOLDSV in the temporal pole. Lower BOLDSV in the orofacial M1/S1 regions was correlated with higher clinical pain and higher sensitivity of the masseter muscle pain. The study also found that the catechol-O-methyltransferase (COMT) Val158Met polymorphism was associated with lower BOLDSV in the dlPFC and higher BOLDSV in the temporal pole. The number of Met alleles was associated with lower dlPFC and greater temporal pole BOLDSV in both healthy controls and TMD groups.


PUBCHEM.COMPOUND:86294693

lower levels in orofacial M1/S1 regions correlate with higher pain


NCBIGene:1312

associated with lower levels in dlPFC and higher levels in temporal pole


CHEBI:35482

The study found that new persistent opioid use after major surgery in opioid-naive patients is associated with increased health care utilization and costs in the year after surgery across all surgical settings and payers. Patients with new persistent opioid use had more inpatient admissions, emergency department visits, and ambulance/paramedic service use than patients without persistent use. They also had approximately 5 times more opioid prescriptions and more nonopioid pharmacy claims.


CHEBI:35482

The study used preoperative claims data to predict postoperative opioid use in opioid-naïve patients. The study found that non-linear models were slightly better at predicting refills than linear models. Major surgery, opioid prescriptions within 30 days prior to surgery, and abdominal pain were significant predictors of refills. Back/joint/head pain were the most important features in predicting new persistent use.


CHEBI:35482


CHEBI:35482

The study investigates patients' perspectives on postoperative opioid use after minor elective hand surgery. The authors found that patients actively sought out protective mechanisms to decide on opioid use, often avoiding opioids due to the risk of addiction and the associated stigma. The study suggests that understanding patients' decision-making processes is crucial for developing patient-centered strategies to address the opioid epidemic.


MONDO:0002081

The study tested the feasibility and acceptability of a Screening, Brief Intervention, and Referral to Treatment for Pain Management intervention (SBIRT-PM) among Veterans with chronic pain due to musculoskeletal disorders. The intervention involved up to four sessions of telephone-based counseling using a motivational interviewing framework. The study found that the majority of the Veterans screened positive for comorbid depression and problematic substance use. The intervention was well-received with 80% of participants engaging in at least one session and 90% completing the post-assessment. Participants reported satisfaction with learning about new pain care services, obtaining assistance connecting to services, and receiving support from their counselors.


HP:0012532


UniProtKB:P13906


MESH:D016578

The study investigated the safety and efficacy of lorcaserin, a serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonist, in participants with cocaine use disorder (CocUD). The results showed that lorcaserin was safe when administered with cocaine, with no significant interactions on cardiovascular measures, plasma cocaine levels, or subjective ratings. However, lorcaserin did not effectively reduce the reinforcing effects of cocaine. Interestingly, it was found that lorcaserin significantly decreased ratings of irritability, hunger, and craving, but participants treated with lorcaserin were more likely to choose cocaine over money.


MESH:D016578


MESH:C502494

The study examined the prevalence of opioid use disorder and willingness to engage in treatment among clients of eight mental health outpatient clinics in Los Angeles County. It was found that 8% had a probable prescription opioid use disorder and 2% a probable heroin use disorder. Among those with probable prescription opioid use disorder, 78% had never received any treatment, and 82% had never taken a medication for this disorder. The strongest predictor of willingness to take a medication was believing that it would help stop opioid use.


CHEBI:35482

The paper discusses the impact of the opioid crisis on the ongoing suicide crisis among American Indian and Alaska Native (AIAN) communities. The study uses data from the Centers for Disease Control and Prevention to report trends of opioid overdose and suicide for AIAN and non-AIAN populations. The findings reveal alarming and potentially correlated trends of opioid use and suicidality among AIAN populations. The paper emphasizes the need for research to understand and address the intersection between opioid and suicide risk and protective factors to inform prevention and intervention efforts among AIAN populations.


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


NCBIGene:3107


NCBIGene:2547


PR:000008664


CHEBI:35482

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.


HP:0030858


MONDO:0002050


CHEBI:35482

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.


MONDO:0001225

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.


MONDO:0011685

Mental and behavioral disorders due to polysubstance use


MONDO:0004995


CHEBI:36416


CHEBI:35482

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.


CHEBI:35482

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.


UBERON:0025261

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.


CHEBI:35482

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.


UBERON:2001186

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.


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


NCBITaxon:1485


NCBIGene:100885778


MESH:C006136

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.


MESH:C006136

prevents and reverses nociceptive behaviors induced by


MESH:C006136


NCIT:C171940

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.


NCIT:C13257


MESH:C454676

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.


MESH:C055140

longer hospital stay and duration of treatment compared to Phenobarbital


MESH:C454676


MESH:C523259

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.


MESH:C560330


MESH:C541946

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.


MESH:C541946


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.


PR:000005715


PR:000003388


PR:000050122


UBERON:0011769

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.


NCBIGene:21331


UBERON:0011769


MONDO:0033818

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


UBERON:0004469

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.


MESH:D005223


UBERON:0011769

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)


HP:0009126

Degenerative intervertebral disc (IVD) pathology

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.


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.


CHEBI:25367


CHEBI:35480


CHEBI:33659


CHEBI:59999


GO:0048546


NCIT:C103223


HP:0033623


MESH:D000069196


NCBIGene:34727

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.


MESH:C560330


CHEBI:35482

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.


PUBCHEM.COMPOUND:15981237

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.


NCIT:C41333

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.


MONDO:0043988

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.


MESH:C049622

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.


MESH:C049622

Adaptive compartments of the immune system


MESH:C049622


NCIT:C120615

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.


MESH:C502494

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.


MESH:C502494


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


MONDO:0044745


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.


CHEBI:33731


PR:000001376

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.


PR:000013266


NCIT:C120615

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.


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.


PR:000021962


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:90477108

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


UNII:D9K3SN2LNY


MESH:D014612


NCIT:C159854


PR:000050373


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


MESH:D022681

Diphtheria, tetanus, and acellular pertussis (DTaP) vaccine


PR:000008963

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.


PR:000008963


PUBCHEM.COMPOUND:90477108