Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors DOI Creative Commons
Mariacristina Mazzitelli, Peyton Presto, Nico Antenucci

и другие.

Cells, Год журнала: 2022, Номер 11(16), С. 2608 - 2608

Опубликована: Авг. 21, 2022

Metabotropic glutamate receptors (mGluR or mGlu) are G-protein coupled activated by the binding of glutamate, main classical neurotransmitter nervous system. Eight different mGluR subtypes (mGluR1-8) have been cloned and classified in three groups based on their molecular, pharmacological signaling properties. mGluRs mediate several physiological functions such as neuronal excitability synaptic plasticity, but they also implicated numerous pathological conditions including pain. The availability new more selective allosteric modulators together with canonical orthosteric ligands transgenic technologies has led to significant advances our knowledge about role specific pathophysiological mechanisms various diseases. Although development successful compounds acting for clinical use scarce, subtype-specific-pharmacological manipulation might be a compelling approach treatment disorders humans, pain; this review aims summarize update preclinical evidence roles pain system discusses gaps regarding mGluR-related sex differences neuroimmune

Язык: Английский

Acute inflammatory response via neutrophil activation protects against the development of chronic pain DOI Open Access
Marc Parisien, L. Lima, Concetta Dagostino

и другие.

Science Translational Medicine, Год журнала: 2022, Номер 14(644)

Опубликована: Май 11, 2022

The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying low back (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with LBP, followed for 3 months. Transcriptomic changes were compared between patients whose LBP was resolved at months those persisted. We found thousands dynamic transcriptional over none persistent pain. Transient neutrophil-driven up-regulation inflammatory responses protective against In mouse assays, early treatment a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led prolonged despite being analgesic short term; such prolongation observed other analgesics. Depletion neutrophils delayed resolution mice, whereas injection themselves, S100A8/A9 proteins normally released by neutrophils, prevented development long-lasting induced an drug. Analysis trajectories human subjects reporting UK Biobank identified elevated risk persistence taking NSAIDs. Thus, efficacy time points, management inflammation may be counterproductive long-term outcomes sufferers.

Язык: Английский

Процитировано

218
The anatomy of pain and suffering in the brain and its clinical implications DOI Creative Commons
Dirk De Ridder, Divya Adhia, Sven Vanneste

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2021, Номер 130, С. 125 - 146

Опубликована: Авг. 16, 2021

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Chronic pain, a prevalence of 20-30 % the major cause human suffering worldwide, because effective, specific safe therapies have yet to be developed. It unevenly distributed among sexes, women experiencing more pain suffering. can anatomically phenomenologically dissected into three separable but interacting pathways, lateral 'painfulness' pathway, medial 'suffering' pathway descending inhibitory pathway. One may pain(fullness) without pain(fullness). sensation leads via cognitive, autonomic processing, expressed as anger, fear, frustration, anxiety depression. The overlaps salience stress networks, explaining that behavioural relevance meaning determines painfulness. Genetic epigenetic influences trigger chronic neuroinflammatory changes which are involved in transitioning from acute pain. Based on concept Bayesian brain, (and suffering) regarded consequence imbalance between two ascending pathways under control reward system. therapeutic clinical implications this simple model obvious. After categorizing working mechanisms each available treatments (pain killers, psychopharmacology, psychotherapy, neuromodulation, psychosurgery, spinal cord stimulation) 1 3 rational combination proposed activating inhibition so rebalance pathways.

Язык: Английский

Процитировано

162
Stress-induced biological aging: A review and guide for research priorities DOI Creative Commons

Lilian R. Polsky,

Kelly E. Rentscher, Judith Carroll

и другие.

Brain Behavior and Immunity, Год журнала: 2022, Номер 104, С. 97 - 109

Опубликована: Июнь 1, 2022

Exposure to chronic adverse conditions, and the resultant activation of neurobiological response cascade, has been associated with an increased risk early onset age-related disease and, recently, older biological age. This body research led hypothesis that exposure stressful life experiences, when occurring repeatedly or over a prolonged period, may accelerate rate at which ages. The mechanisms through psychosocial stress influences distinct aging pathways alter rates likely involve multiple layers in physiological-molecular network. In this review, we integrate using animal, human, vitro models begin delineate impact aging, as well neuroendocrine mediators (i.e., norepinephrine, epinephrine, glucocorticoids) drive these effects. Findings highlight key connections between namely cellular metabolic activity, DNA damage, telomere length, senescence, inflammatory patterns. We conclude guiding framework conceptual model outlines most promising by conditions could point missing gaps knowledge where future best answer pressing questions.

Язык: Английский

Процитировано

76
Reducing IgG accumulation via neonatal Fc receptor (FcRn) blockade relieves neuropathic pain DOI Creative Commons
Nathan T. Fiore,

Kendal F. Willcox,

Dorsa Dayani

и другие.

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

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
Sestrin2 overexpression attenuates osteoarthritis pain via induction of AMPK/PGC-1α-mediated mitochondrial biogenesis and suppression of neuroinflammation DOI Creative Commons
Jia Sun,

Fan‐He Song,

Jiayi Wu

и другие.

Brain Behavior and Immunity, Год журнала: 2022, Номер 102, С. 53 - 70

Опубликована: Фев. 10, 2022

Язык: Английский

Процитировано

67
Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β DOI Creative Commons
Paul A. Boakye, Shaojun Tang, Peter A. Smith

и другие.

Frontiers in Pain Research, Год журнала: 2021, Номер 2

Опубликована: Авг. 25, 2021

Intractable neuropathic pain is a frequent consequence of nerve injury or disease. When peripheral nerves are injured, damaged axons undergo Wallerian degeneration. Schwann cells, mast fibroblasts, keratinocytes and epithelial cells activated leading to the generation an "inflammatory soup" containing cytokines, chemokines growth factors. These primary mediators sensitize sensory endings, attract macrophages, neutrophils lymphocytes, alter gene expression, promote post-translational modification proteins, ion channel function in afferent neurons. This leads increased excitability spontaneous activity secondary including colony stimulating factor 1 (CSF-1), chemokine C-C motif ligand 21 (CCL-21), Wnt3a, Wnt5a. Release these from neurons alters properties spinal microglial causing them release tertiary mediators, many situations

Язык: Английский

Процитировано

59
Neuroimmune Mechanisms Underlying Neuropathic Pain: The Potential Role of TNF-α-Necroptosis Pathway DOI Open Access

Yi-Wen Duan,

Shaoxia Chen,

Qiaoyun Li

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(13), С. 7191 - 7191

Опубликована: Июнь 28, 2022

The neuroimmune mechanism underlying neuropathic pain has been extensively studied. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine that drives storm and stimulates cascade of other cytokines in pain-related pathways, induces modulates by facilitating peripheral (primary afferents) central (spinal cord) sensitization. Functionally, TNF-α controls the balance between cell survival death inducing an inflammatory response two programmed mechanisms (apoptosis necroptosis). Necroptosis, novel form death, is receiving increasing attraction may trigger neuroinflammation to promote pain. Chronic often accompanied adverse pain-associated emotional reactions cognitive disorders. Overproduction supraspinal structures such as anterior cingulate cortex (ACC) hippocampus plays important role disorders memory deficits also participates modulation transduction. At present, studies reporting on TNF-α–necroptosis pathway are lacking. This review indicates research prospects this based its anxiety, depression associated with neurodegenerative diseases. In addition, we have summarized related mediated discussed detail, which represent avenue for future therapeutic intervention.

Язык: Английский

Процитировано

59
Sex differences in pain along the neuraxis DOI Creative Commons
Peyton Presto, Mariacristina Mazzitelli,

Riley Junell

и другие.

Neuropharmacology, Год журнала: 2022, Номер 210, С. 109030 - 109030

Опубликована: Март 21, 2022

Язык: Английский

Процитировано

54
Cannabidiol alleviates neuroinflammation and attenuates neuropathic pain via targeting FKBP5 DOI
Xue Wang, Cong Lin, Sha Jin

и другие.

Brain Behavior and Immunity, Год журнала: 2023, Номер 111, С. 365 - 375

Опубликована: Май 15, 2023

Язык: Английский

Процитировано

35
Neuropathic pain; what we know and what we should do about it DOI Creative Commons
Peter A. Smith

Frontiers in Pain Research, Год журнала: 2023, Номер 4

Опубликована: Сен. 22, 2023

Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve promotes Schwann cell activation and invasion immunocompetent cells into site injury, spinal cord higher sensory structures such as thalamus cingulate cortices. Various cytokines, chemokines, growth factors, monoamines neuropeptides effect two-way signalling between neurons, glia immune cells. This sustained hyperexcitability spontaneous activity in primary afferents that crucial for onset persistence well misprocessing information supraspinal structures. Much current understanding aetiology identification drug targets derives studies consequences peripheral rodent models. Although a vast amount has been forthcoming, translation this clinical arena minimal. Few, if any, major therapeutic approaches have appeared since mid 1990's. may reflect failure recognise differences processing males vs. females, cellular responses different types humans animals. Basic science which seek bridge knowledge gap include better assessment animal models, use models emulate human disease, stratification phenotypes according quantitative signs symptoms disease. lead more personalized effective treatments individual patients. Significance statement: There an urgent need find new neuropathic pain. classical revealed essential features central sensitization some molecular mechanisms involved, they do not adequately model multiplicity states injuries bring forth clinic. review seeks integrate disciplines understand pain; including immunology, biology, electrophysiology biophysics, anatomy, neurology, pharmacology behavioral science. Beyond this, it underlines ongoing refinements basic practice will engender improved management.

Язык: Английский

Процитировано

24