Innovative therapeutic strategies using ADHD medications tailored to the behavioral characteristics of patients with chronic pain

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 26, 2025

Chronic pain affects a significant portion of adults and is linked to psychosocial issues, cognitive dysfunction, psychiatric disorders, complicating treatment. Attention deficit hyperactivity disorder (ADHD) increasingly recognized as contributing factor chronic pain, particularly nociplastic with notable prevalence comorbidity between ADHD conditions like fibromyalgia low back pain. behaviors such impulsivity overactivity can exacerbate by leading patients seek risky treatments or discontinue care prematurely. medications are expected alleviate severity improving associated dysfunction addressing central sensitization, fundamental mechanism in Brain abnormalities contribute increased spontaneous activity the anterior cingulate cortex-posterior insular pathway due neuroinflammation, alterations action potential firing, changes transmission pathways spinal dorsal horn. Additionally, norepinephrine synthesis reduced efficiency amplify nociceptive information from periphery facilitate sensitization ADHD. Beyond typical stimulants, reuptake inhibitors, alpha-2 receptor agonists, various antidepressants, mood stabilizers, antipsychotics, Parkinson's disease medications, antidementia have proven effective alleviating symptoms. These for ADHD, may offer innovative solutions managing targeting both cognitive/behavioral observed comorbid Further research into these mechanisms could lead new, more pharmacological condition that often overlooked.

Язык: Английский

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A quantitative weight-of-evidence review of preclinical studies examining the potential developmental neurotoxicity of acetaminophen

Critical Reviews in Toxicology, Год журнала: 2025, Номер unknown, С. 1 - 55

Опубликована: Фев. 21, 2025

Acetaminophen [paracetamol; N-acetyl-para-aminophenol (APAP)] is an antipyretic/analgesic commonly used in the treatment of fever and mild to moderate pain, headache, myalgia, dysmenorrhea. Recent literature has questioned safety acetaminophen use during pregnancy, with emphasis on whether exposure developing nervous system results behavioral changes consistent autism spectrum disorder (ASD), attention-deficit/hyperactivity (ADHD), and/or other cognitive deficits offspring. No previous review a fully detailed, quantitative weight-of-evidence (QWoE) approach critically examine preclinical data regards potential developmental neurotoxicity (DNT). Following regulatory guidance, QWoE framework using prespecified scoring criteria was developed approaches characterize adverse DNT outcomes considerations for biological relevance response (outcome score) strength methods study design (methods score). Considerations score included (1) experimental design, (2) details/reliability measurement(s), (3) transparency, (4) translational/methodological relevance. outcome response-related statistical significance, dose-response, relevance/reliability/magnitude, plausibility, (5) translational relevance, including consideration systemic toxicity/hepatotoxicity therapeutic non-systemically toxic doses durations use. Application this 34 vivo studies identified that assess resulted 188 entries documented across 11 endpoints: social behavior, stereotypic rigidity, attention/impulsivity, hyperactivity, anxiety-like sensorimotor function, spatial learning/memory, nonspatial neuroanatomy, neurotransmission. For each endpoint, mean were calculated total segregated by sex assist determining quality adversity. Informed all entries, analysis demonstrated showing no evidence male female rodents following at nonsystemically doses. Although some endpoints (behavioral neurotransmission) generally displayed more limited dataset relatively lower quality, similar conclusions drawn based indicating lack reliability reported effects. Overall, demonstrates effects structure function system, neuroanatomical, neurotransmission, endpoints.

Язык: Английский

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From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Фев. 16, 2023

Alzheimer's disease (AD) is the most common neurodegenerative disorder with majority of patients classified as sporadic AD (sAD), in which etiopathogenesis remains unresolved. Though sAD argued to be a polygenic disorder, apolipoprotein E (APOE) ε4, was found three decades ago pose strongest genetic risk for sAD. Currently, only clinically approved disease-modifying drugs are aducanumab (Aduhelm) and lecanemab (Leqembi). All other treatment options purely symptomatic modest benefits. Similarly, attention-deficit hyperactivity (ADHD), one neurodevelopmental mental disorders children adolescents, acknowledged persist adulthood over 60% patients. Moreover, ADHD whose not completely understood, large proportion respond well (first-line psychostimulants, e.g., methylphenidate/MPH), however, no therapy exists. Interestingly, cognitive impairments, executive, memory deficits seem ADHD, but also early stages mild impairment (MCI), dementia, including Therefore, many hypotheses that might have similar origins or they intercalate another, shown recently may considered factor Intriguingly, several overlaps been between two disorders, inflammatory activation, oxidative stress, glucose insulin pathways, wingless-INT/mammalian target rapamycin (Wnt/mTOR) signaling, altered lipid metabolism. Indeed, Wnt/mTOR activities were modified by MPH studies. play role animal models disorder. MCI phase successful apathy some improvement cognition, according recent meta-analysis. In models, ADHD-like behavioral phenotypes observed indicating possible interconnection AD. this concept paper, we will discuss various evidence human supporting hypothesis increase sAD, involvement Wnt/mTOR-pathway leading lifespan alteration at neuronal levels.

Язык: Английский

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Deep-Learning-Based Analysis Reveals a Social Behavior Deficit in Mice Exposed Prenatally to Nicotine

Cells, Год журнала: 2024, Номер 13(3), С. 275 - 275

Опубликована: Фев. 1, 2024

Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us assess behavioral phenotypes animal models without cognitive bias manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their using DeepLabCut SimBA. We optimized training parameters for pose estimation succeeded labeling a single-mouse or two-mouse model high fidelity free-moving behavior. applied trained network analyze behavior found that PNE exhibited impulsivity lessened working memory, which are characteristics ADHD. also showed elevated anxiety deficits social interaction, reminiscent autism spectrum (ASD). further examined by evaluating adult neurogenesis hippocampus, pathological hallmark ASD, demonstrated newborn neurons were decreased, specifically ventral part reported related emotional behaviors. These results support hypothesis risk factor comorbidity ADHD ASD mice.

Язык: Английский

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Telencephalon Organoids Derived from an Individual with ADHD Show Altered Neurodevelopment of Early Cortical Layer Structure

Stem Cell Reviews and Reports, Год журнала: 2023, Номер 19(5), С. 1482 - 1491

Опубликована: Март 6, 2023

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental that occurs in early childhood and can persist to adulthood. It affect many aspects of patient's daily life, so it necessary explore the mechanism pathological alterations. For this purpose, we applied induced pluripotent stem cell (iPSC)-derived telencephalon organoids recapitulate alterations occurring cerebral cortex ADHD patients. We found showed less growth layer structures than control-derived organoids. On day 35 differentiation, thinner ADHD-derived contained more neurons those Furthermore, decrease proliferation during development from 56. 56 there was significant difference proportion symmetric asymmetric division between control groups. In addition, observed increased apoptosis development. These results show characteristics neural cells formation structures, which might indicate key roles pathogenesis ADHD. Our exhibit cortical developmental neuroimaging studies, providing an experimental foundation for understanding mechanisms Graphical

Язык: Английский

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Reduced dopamine transporter availability in drug‐naive adult attention‐deficit/hyperactivity disorder

Psychiatry and Clinical Neurosciences Reports, Год журнала: 2024, Номер 3(1)

Опубликована: Фев. 18, 2024

Abstract Aim This study aimed to clarify the abnormalities in dopamine transporter (DAT) availability drug‐naive adult patients with attention‐deficit/hyperactivity disorder (ADHD) and relationship between ADHD symptoms DAT availability. Methods Single‐photon emission tomography (SPECT) was performed using iodine‐123‐β‐carbomethoxy‐3β‐(4‐iodophenyltropane) (I‐123 β CIT) as a tracer measure vivo 20 [mean age ± standard deviation (SD)]: 25 3.44 years; male:female = 11:9] age‐ sex‐matched healthy controls (HCs) (mean SD: 23.9 2.27 years). Comparisons of HCs association symptom severity within group were analyzed Statistical Parametric Mapping 12. Results Drug‐naive adults showed significantly reduced bilateral nucleus accumbens compared HCs. Correlation analyses revealed negative correlation inattentive heads caudate nucleus, indicating severe lower nucleus. Conclusion In ADHD, accumbens, an important part reward system. finding indicates importance system pathogenesis ADHD. Inattentiveness associated suggesting involvement cortico‐striato‐thalamo‐cortical circuit.

Язык: Английский

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A HIDDEN MARK OF A TROUBLED PAST: NEUROIMAGING AND TRANSCRIPTOMIC ANALYSES REVEAL INTERACTIVE EFFECTS OF MATERNAL IMMUNE ACTIVATION AND ADOLESCENT THC EXPOSURE SUGGESTIVE OF INCREASED NEUROPSYCHIATRIC RISK

Biological Psychiatry Global Open Science, Год журнала: 2025, Номер 5(3), С. 100452 - 100452

Опубликована: Янв. 23, 2025

Maternal exposure to infections during gestation has been shown predispose individuals neuropsychiatric disorders. Additionally, clinical data suggest that cannabis use may trigger the onset of schizophrenia in vulnerable individuals. However, direction causality remains unclear. To elucidate this issue, we utilized a rat model maternal immune activation combined with increasing doses Δ9-tetrahydrocannabinol adolescence both male and female rats. We investigated several behaviors adulthood relevant for disorders, including impairments working memory, deficits sensorimotor gating, alterations social behavior, anhedonia, potential changes implicit learning (conditioned taste aversion). Furthermore, conducted longitudinal positron emission tomography study target affected brain regions and, subsequently, collected samples one such region (the orbitofrontal cortex) RNA sequencing analyses, which were also performed on peripheral blood mononuclear cells identify biomarkers. While adolescent did not unmask latent behavioral disruptions, scans revealed dependent combination hits. transcriptomic studies demonstrated dopaminergic, glutamatergic, serotoninergic genes, exposures most cases shifting expression from downregulation upregulation. In cells, interactive effects observed inflammatory pathways, some genes proposed as These results these 2 vulnerability factors leaves lasting mark body, potentially predisposing disorders even before manifest.

Язык: Английский

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Animal Models of Addiction

Oxford University Press eBooks, Год журнала: 2025, Номер unknown, С. 651 - 660

Опубликована: Янв. 1, 2025

Abstract Substance use disorders (SUDs) are characterized by chronic relapsing episodes of drug seeking and/or taking, often despite negative outcomes. Although animal models cannot recapitulate all aspects SUDs because the complexities societal interactions and human-specific processing rewards affect, there many components that can be effectively modeled. This chapter reviews key concepts, advantages, caveats using to study initiation, maintenance, escalation taking adverse consequences, abstinence relapse. The discusses have direct translational impact where interpretation limitations. It also used interrogate both genetic environmental factors influencing vulnerability at different stages SUD. Animal made important contributions current knowledge drug-mediated responses adaptations brain circuitry could never been acquired via human research.

Язык: Английский

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Hippocampus under Pressure: Molecular Mechanisms of Development of Cognitive Impairments in SHR Rats

Biochemistry (Moscow), Год журнала: 2024, Номер 89(4), С. 711 - 725

Опубликована: Апрель 1, 2024

Язык: Английский

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Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Апрель 4, 2023

Abstract Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute chronification, dysfunction of systems in nervous system relevant to ADHD symptoms. Noxious stimuli-induced (NSIA) measured estimate spontaneously hypertensive rats (SHR) as an model control. Recovery pain-related behaviors after paw incision was assessed. Contributions were examined by vivo microdialysis immunohistochemistry. The SHR showed attenuated NSIA needed a more extended period for recovery from pain. These results suggest patients exhibit chronification due pre-existing analgesia. Immunohistochemistry suggests abnormal noradrenaline turnover downregulation target receptor (alpha2a adrenoceptor). Standard treatment with atomoxetine restored shortened duration hypersensitivity surgery SHR. protocol activated locus coeruleus, origin spinal noradrenaline, both strains, but only control exhibited increase noradrenaline. This result noradrenaline-releasing process be recognized novel mechanism attenuation

Язык: Английский

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