Persistent changes in the dorsal root ganglion nociceptor translatome governs hyperalgesic priming in mice: roles of GPR88 and Meteorin

Pain, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Abstract Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus–detecting sensory neurons, called nociceptors. A key feature of this following priming, stimuli do not normally cause hyperalgesia now readily provoke state. We hypothesized hyperalgesic occurs because reorganization translation mRNA To test hypothesis, we paclitaxel treatment as the stimulus and translating ribosome affinity purification measure persistent changes Na v 1.8+ Translating sequencing revealed 161 genes with persistently altered primed Among these genes, identified Gpr88 upregulated Metrn downregulated. provide functional evidence for related model, interleukin-6 model. GPR88 agonist injection into paw had no effect naive mice but caused mechanical hypersensitivity grimacing responses female mice. Systemic Meteorin completely reversed established prostaglandin E2 Our work demonstrates nociceptor translatomes are causative producing multiple models

Язык: Английский

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Interplay between cannabinoids and the neuroimmune system in migraine

The Journal of Headache and Pain, Год журнала: 2024, Номер 25(1)

Опубликована: Окт. 15, 2024

Migraine is a common and complex neurological disorder that has high impact on quality of life. Recent advances with drugs target the neuropeptide calcitonin gene-related peptide (CGRP) have helped, but treatment options remain insufficient. CGRP released from trigeminal sensory fibers contributes to peripheral sensitization, perhaps in part due actions immune cells trigeminovascular system. In this review, we will discuss potential cannabinoid targeting as an innovative therapeutic for migraine treatment. We cover endogenous endocannabinoids, plant-derived phytocannabinoids synthetically derived cannabinoids. The focus be six types known express multiple receptors: macrophages, monocytes, mast cells, dendritic B T cells. These also contain receptors such, cannabinoids might potentially modulate efficacy current CGRP-targeting drugs. Unfortunately, date most studies relied cell cultures only single preclinical study tested model. Encouragingly, created stable chiral analog endocannabinoid reduced meningeal degranulation. Likewise, clinical trials evaluating safety cannabinoid-based therapies patients been limited are encouraging. Thus, field at its infancy there significant gaps our understanding migraine. Future research exploring interactions between could lead more targeted effective treatments.

Язык: Английский

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The role of androgens in migraine pathophysiology

Neurobiology of Pain, Год журнала: 2024, Номер 16, С. 100171 - 100171

Опубликована: Июль 1, 2024

Migraine affects ∼12 % of the worldwide population and is more prevalent in females, which suggests a role sex hormones migraine pathophysiology. Most studies have focused on estrogen progesterone, involvement androgens has been less studied. However, due to recent advances androgen interventions, could advance new androgen-based treatments, it critical better understand migraine. Testosterone, most studied androgen, was found an antinociceptive effect various animal human pain studies. Thus, also protective related lower severity prevalence. In this review, we discuss examining migraine-related symptoms models. Additionally, summarize results comparing levels between patients with healthy controls, assessing relationships severity, intervention impact testosterone treatment severity. Many limitations, however, suggest that may minor Still, possible are involved pathophysiology sub-group such as adolescents or postmenopausal women. We potential mechanisms testosterone, main tested, can These range from cellular level systems behavior include sensory neurons, immune vascular systems, stress response, brain function, mood. Lastly, future directions line research.

Язык: Английский

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The Effects of Socioeconomic Position on Endogenous Pain Modulation: A Quasi-Experimental Approach

Journal of Pain, Год журнала: 2025, Номер unknown, С. 104778 - 104778

Опубликована: Янв. 1, 2025

Язык: Английский

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Emotional Impairments in Animal Models of Traumatic Neuropathic Pain: Where Do We Stand?

Biological Psychiatry Global Open Science, Год журнала: 2025, Номер 5(1), С. 100424 - 100424

Опубликована: Янв. 1, 2025

Язык: Английский

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Androgen receptors expressed in the primary sensory neurons regulate mechanical pain sensitivity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Summary The expression of hormonal receptors in pain-processing regions complicates understanding the effects on pain mechanisms. This study investigates androgen receptor (AR) involvement sensitivity and sex differences perception. Mechanical thresholds were higher normal male mice compared to gonadectomized (GDX) female mice, correlating with serum testosterone levels. In dorsal root ganglia (DRG), AR was expressed males but undetectable GDX females. sensory neuron-selective conditional knockout (AR-cKO) mechanical significantly lower than wild-type males. administration propionate or dihydrotestosterone raised thresholds, accompanied by increased DRG. effect abolished AR-cKO females, consistent findings. These results indicate that primary neurons are critical targets signaling regulating sensitivity.

Язык: Английский

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A look into the future: Your biological sex may guide chronic pain treatment

Neuron, Год журнала: 2025, Номер 113(6), С. 800 - 802

Опубликована: Март 1, 2025

Язык: Английский

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How microglia contribute to the induction and maintenance of neuropathic pain

Nature reviews. Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

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Pain kept under wraps of myelin sheath

Frontiers in Pain Research, Год журнала: 2025, Номер 6

Опубликована: Апрель 23, 2025

The myelin sheath serves both as insulator and metabolic powerhouse for large-diameter dorsal root ganglia (DRG) neurons-some of the longest cells in body-transmitting sensory impulses from periphery to spinal cord. When is damaged, bioactive fragments basic protein (MBP) are released, playing a pivotal role pathological pain. MBP-derived peptides (MBPd) emerge ubiquitous yet sex-specific mediator In females, MBPd triggers widespread transcriptional response across peripheral nerve, DRG, cord, leading persistent, treatment-resistant tactile allodynia-pain normally innocuous touch. contrast, males exhibit only localized response, confined which does not extend DRG or cord induce sex difference driven by MBPd's interaction with lipids regulation nuclear receptor transcription factors, including estrogen (ESR) liver X (LXR)/retinoid × (RXR) complex-key regulators lipid cholesterol metabolisms mounting sex-dependent immunity. By unraveling these fundamental mechanisms remodeling, this work opens door innovative, non-addictive, personalized therapeutics diagnostics chronic

Язык: Английский

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A recent history of immune cell sex differences in the peripheral nervous system in persistent pain states

Brain Behavior and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Pain is entwined with inflammation, and biological sex often influences mechanisms of the immune system. Due to possible differences in inflammatory mechanisms, women are predisposed autoimmune diseases chronic pain. Despite as a critical variable clinical cases conditions its pain comorbidities, fundamental investigations have long underrepresented female subjects their studies. Fundamental research 2010 s, however, identified binary specific mechanism for rodents: male microglia-driven while T cell-driven. Since then, studies expanded neuro-immunology indicate that cells involved these processes take on more elaborate roles when other causal modalities anatomical levels neuropathic In this mini-review, we highlight updated macrophages, cells, B peripheral nervous system during persistent conditions: We discuss similarities cell types. By parsing out states may be better positioned find immune-based therapies can effectively target sex-biased conditions.

Язык: Английский

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