Mapping the neuroethological signatures of pain, analgesia, and recovery in mice

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2811 - 2830.e8

Published: July 12, 2023

Language: Английский

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Pathology of pain and its implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 8, 2024

Abstract Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management crucial for individuals suffering from pain. However, current methods assessment treatment fall short clinical needs. Benefiting advances in neuroscience biotechnology, neuronal circuits molecular mechanisms critically involved modulation have been elucidated. These research achievements incited progress identifying new diagnostic therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting stage subsequent contents. The review next delves into underlying disorders, including gene mutation, epigenetic modification, posttranslational inflammasome, signaling pathways microbiota. To better present a comprehensive view research, two prominent issues, sexual dimorphism comorbidities, are discussed detail based on findings. status quo evaluation manipulation summarized. A series improved innovative strategies, such as therapy, monoclonal antibody, brain-computer interface microbial intervention, making strides towards application. We highlight existing limitations future directions enhancing quality preclinical research. Efforts decipher complexities pathology will be instrumental translating scientific discoveries practice, thereby improving bench bedside.

Language: Английский

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Sex differences in mechanisms of pain hypersensitivity

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 163, P. 105749 - 105749

Published: June 3, 2024

The introduction of sex-as-a-biological-variable policies at funding agencies around the world has led to an explosion very recent observations sex differences in biology underlying pain. This review considers evidence sexually dimorphic mechanisms mediating pain hypersensitivity, derived from modern assays persistent rodent animal models. Three well-studied findings are described detail: male-specific role spinal cord microglia, female-specific calcitonin gene-related peptide (CGRP), and prolactin its receptor. Other sex-specific molecular involvement subjected pathway analyses reveal least one novel hypothesis: that females may preferentially use Th1 males Th2 T cell activity mediate chronic

Language: Английский

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Neuronal G protein-gated K⁺ channels

AJP Cell Physiology, Journal Year: 2022, Volume and Issue: 323(2), P. C439 - C460

Published: June 15, 2022

G protein-gated inwardly rectifying K + (GIRK/Kir3) channels exert a critical inhibitory influence on neurons. Neuronal GIRK mediate the protein-dependent, direct/postsynaptic effect of many neurotransmitters including γ-aminobutyric acid (GABA), serotonin, dopamine, adenosine, somatostatin, and enkephalin. In addition to their complex regulation by proteins, neuronal channel activity is sensitive phosphatidylinositol 4,5-bisphosphate (PIP 2 ), phosphorylation, regulator protein signaling (RGS) intracellular Na Ca 2+ , cholesterol. The application genetic viral manipulations in rodent models, together with recent progress development modulators, has increased our understanding physiological behavioral impact channels. Work models also revealed that modified, transiently or persistently, various stimuli exposure drugs abuse, changes patterns, aversive experience. A growing body preclinical clinical evidence suggests dysregulation contributes neurological diseases disorders. primary goals this review are highlight fundamental principles biology, mechanisms plasticity, nascent landscape pharmacology, potential relevance pathophysiology treatment

Language: Английский

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Machine learning and artificial intelligence in neuroscience: A primer for researchers

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 115, P. 470 - 479

Published: Nov. 14, 2023

Artificial intelligence (AI) is often used to describe the automation of complex tasks that we would attribute to. Machine learning (ML) commonly understood as a set methods develop an AI. Both have seen recent boom in usage, both scientific and commercial fields. For community, ML can solve bottle necks created by complex, multi-dimensional data generated, for example, functional brain imaging or *omics approaches. here identify patterns could not been found using traditional statistic However, comes with serious limitations need be kept mind: their tendency optimise solutions input means it crucial importance externally validate any findings before considering them more than hypothesis. Their black-box nature implies decisions usually cannot understood, which renders use medical decision making problematic lead ethical issues. Here, present introduction curious field ML/AI. We explain principles well methodological advancements discuss risks what see future directions field. Finally, show practical examples neuroscience illustrate ML.

Language: Английский

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Representation and control of pain and itch by distinct prefrontal neural ensembles

Neuron, Journal Year: 2023, Volume and Issue: 111(15), P. 2414 - 2431.e7

Published: May 23, 2023

Language: Английский

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Normative Preclinical Algesiometry Data on the von Frey and Radiant Heat Paw-Withdrawal Tests: An Analysis of Data from More Than 8,000 Mice Over 20 Years

Journal of Pain, Journal Year: 2024, Volume and Issue: 25(7), P. 104468 - 104468

Published: Jan. 12, 2024

The measurement of withdrawal to experimenter-delivered mechanical stimuli (von Frey test) and heat (radiant paw-withdrawal or Hargreaves' applied the hind paws is ubiquitous in preclinical pain research, but no normative values for most-common applications these tests have ever been published. We analyzed a retrospective data set thresholds latencies 8,150 mice which measures were taken using replicate determinations, before after injection inflammatory substances experimental nerve damage producing hypersensitivity, totaling 97,332 measurements. All tested same physical laboratory over 20-year period similar equipment procedures. nonetheless find evidence large interindividual variability, affected by tester, genotype, mouse sex, tester order, injury. These factors are discussed, we believe that will serve as useful reference expected testing. PERSPECTIVE: This article presents analysis von radiant (Hargreaves' measurements collected single 20 years. In addition serving guide, sources variability identified including sex.

Language: Английский

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Sickle Cell Disease Update: New Treatments and Challenging Nutritional Interventions

Nutrients, Journal Year: 2024, Volume and Issue: 16(2), P. 258 - 258

Published: Jan. 15, 2024

Sickle cell disease (SCD), a distinctive and often overlooked illness in the 21st century, is congenital blood disorder characterized by considerable phenotypic diversity. It comprises group of disorders, with sickle anemia (SCA) being most prevalent serious genotype. Although there have been some systematic reviews global data, worldwide statistics regarding SCD prevalence, morbidity, mortality remain scarce. In developed countries lower number patients, cutting-edge technologies led to development new treatments. However, developing settings where (SCD) more prevalent, medical management, rather than cure, still relies on use hydroxyurea, transfusions, analgesics. This that affects red cells, consequently affecting organs diverse manners. We discuss its etiology advent technologies, but aim this study understand various types nutrition-related studies involving individuals suffering from SCD, particularly Africa. The interplay environment, food, gut microbiota, along their respective genomes collectively known as microbiome, host metabolism responsible for mediating metabolic phenotypes modulating microbiota. addition, it serves purpose providing essential nutrients. Moreover, engages direct interactions homeostasis immune system, well indirect via metabolites. Nutrition interventions nutritional care are mechanisms addressing increased nutrient expenditures important aspects supportive management patients SCD. Underprivileged areas Sub-Saharan Africa should be accompanied efforts define promote Their importance key maintaining well-being quality life, especially because products limited, while native medicinal plant resources acknowledged.

Language: Английский

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Using in vivo calcium imaging to examine joint neuron spontaneous activity and home cage analysis to monitor activity changes in mouse models of arthritis

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: March 27, 2025

Abstract Background Studying pain in rodent models of arthritis is challenging. For example, assessing functional changes joint neurons challenging due to their relative scarcity amongst all sensory neurons. Additionally, studying behaviors poses its own set difficulties. Commonly used tests, such as static weight-bearing, often require restraint, which can induce stress and consequently alter nociception. The aim this study was evaluate two emerging techniques for investigating mouse rheumatoid- osteo-arthritis: In vivo calcium imaging monitor afferent activity group-housed home cage monitoring assess pain-like behaviors. Specifically, we examined whether there increased spontaneous afferents reduced locomotor following induction arthritis. Methods Antigen induced (AIA) model rheumatoid partial medial meniscectomy (PMX) osteoarthritis. Group-housed behavior mice, weight bearing assessed PMX mice. with GCaMP6s L4 ganglion retrogradely labelled fast blue 2 days AIA 13–15 weeks induction. Cartilage degradation knee sections stained Safranin O green Results produced swelling caused degeneration articular cartilage the knee. first 46 h AIA, mice travelled less distance were mobile compared control mates. contrast, no differences found between sham when measured 4–12 post-surgery. A larger fraction showed but not Spontaneous mostly displayed by medium-sized correlated any Conclusion revealed (with n = 10/group). be multiple

Language: Английский

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Automated preclinical detection of mechanical pain hypersensitivity and analgesia

Pain, Journal Year: 2022, Volume and Issue: 163(12), P. 2326 - 2336

Published: May 11, 2022

Abstract The lack of sensitive and robust behavioral assessments pain in preclinical models has been a major limitation for both research the development novel analgesics. Here, we demonstrate data acquisition analysis platform that provides automated, quantitative, objective measures naturalistic rodent behavior an observer-independent unbiased fashion. technology records freely behaving mice, dark, over extended periods continuous 2 parallel video streams: (1) near-infrared frustrated total internal reflection detecting degree, force, timing surface contact (2) simultaneous ongoing graphing whole-body pose. Using machine vision learning, automatically extract quantify features from these to reveal moment-by-moment changes capture state rodents multiple models. We show voluntary pain-related behaviors are reversible by analgesics analgesia can be objectively differentiated sedation. Finally, used this approach generate paw luminance ratio measure is capturing dynamic mechanical hypersensitivity period scalable high-throughput analgesic efficacy assessment.

Language: Английский

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