Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors DOI Creative Commons
Tyler S. Nelson, Paz Duran, Aida Calderón‐Rivera

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 22, 2024

Abstract Pain is a prominent and debilitating symptom in myotonic disorders, yet its physiological mechanisms remain poorly understood. This study assessed preclinical pain-like behavior murine models of pharmacologically induced myotonia dystrophy type 1 (DM1). In both congenita DM1, impairment the CLCN1 gene, which encodes skeletal muscle voltage-gated CLC-1 chloride channels, reduces ion conductance cells, leading to prolonged excitability delayed relaxation after contraction. We used antagonist anthracene-9- carboxylic acid (9-AC) at intraperitoneal doses 30 or 60 mg/kg HSA LR20b DM1 mice model CLC-1-induced myotonia. Our experimental approach included vivo pain behavioral testing, ex calcium imaging, whole-cell current-clamp electrophysiology mouse dorsal root ganglion (DRG) neurons. A single injection 9-AC mice, persisted for several hours resulted long-lasting allodynic behavior. Similarly, exhibited allodynia hyperalgesia. Despite these behaviors, DRG neurons did not show signs hyperexcitability either model. These findings suggest that induces nociplastic rodents, likely through central sensitization rather than peripheral sensitization. provides insights into pathophysiology disorders highlights potential using explore assess novel analgesics. Future research should focus on involved myotonia-induced develop targeted therapies alleviate this significant clinical burden.

Язык: Английский

Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding DOI
Jonnathan Singh Alvarado, Andrew Lutas,

Joseph C. Madara

и другие.

Neuron, Год журнала: 2024, Номер 112(9), С. 1416 - 1425.e5

Опубликована: Фев. 27, 2024

Язык: Английский

Процитировано

11
Cells and circuits for amygdala neuroplasticity in the transition to chronic pain DOI Creative Commons
Takaki Kiritoshi,

Vadim Yakhnitsa,

Sudhuman Singh

и другие.

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114669 - 114669

Опубликована: Авг. 23, 2024

Maladaptive plasticity is linked to the chronification of diseases such as pain, but transition from acute chronic pain not well understood mechanistically. Neuroplasticity in central nucleus amygdala (CeA) has emerged a mechanism for sensory and emotional-affective aspects injury-induced although evidence comes studies conducted almost exclusively conditions agnostic cell type specificity. Here, we report time-dependent changes genetically distinct projection-specific CeA neurons neuropathic pain. Hyperexcitability CRF projection synaptic parabrachial (PB) input at stage shifted hyperexcitability without non-CRF phase. Accordingly, chemogenetic inhibition PB→CeA pathway mitigated pain-related behaviors acute, chronic, Cell-type-specific temporal neuroplasticity provide neurobiological clinical observation that simply prolonged persistence

Язык: Английский

Процитировано

7
The dorsal column nuclei scale mechanical sensitivity in naive and neuropathic pain states DOI Creative Commons
Aman Upadhyay, Mark A. Gradwell, Thomas J. Vajtay

и другие.

Cell Reports, Год журнала: 2025, Номер 44(4), С. 115556 - 115556

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
Parabrachial neurons promote nociplastic pain DOI Creative Commons
Richard D. Palmiter

Trends in Neurosciences, Год журнала: 2024, Номер 47(9), С. 722 - 735

Опубликована: Авг. 14, 2024

The parabrachial nucleus (PBN) in the dorsal pons responds to bodily threats and transmits alarm signals forebrain. Parabrachial neuron activity is enhanced during chronic pain, inactivation of PBN neurons mice prevents establishment neuropathic, pain symptoms. Chemogenetic or optogenetic activation all glutamatergic PBN, just subpopulation that expresses Calca gene, sufficient establish phenotypes, including long-lasting tactile allodynia, scale with extent stimulation, thereby promoting nociplastic defined as diffuse without tissue inflammation nerve injury. This review focuses on role(s) molecularly downstream nodes brain contribute establishing pain.

Язык: Английский

Процитировано

4
Parabrachial Calca neurons mediate second-order conditioning DOI Creative Commons
Sekun Park, Anqi Zhu, Feng Cao

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 9, 2024

Learning to associate cues, both directly and indirectly, with biologically significant events is essential for survival. Second-order conditioning (SOC) involves forming an association between a previously reinforced conditioned stimulus (CS1) new (CS2) without the presence of unconditioned (US). The neural substrates mediating SOC, however, remain unclear. Parabrachial Calca neurons, which react noxious US, also respond CS after pairing suggesting that neurons mediate SOC. We established aversive SOC behavioral paradigm in mice monitored neuron activity via single-cell calcium imaging during subsequent recall phases. These were activated by CS1 CS2 Chemogenetically inhibiting CS1-CS2 attenuated Thus, reactivation US pathway learned plays important role old CS, promoting formation second-order memories.

Язык: Английский

Процитировано

4
Vagal Sensory Gut–Brain Pathways That Control Eating—Satiety and Beyond DOI
Rebeca Méndez‐Hernández,

Isadora Braga,

Avnika Bali

и другие.

Comprehensive physiology, Год журнала: 2025, Номер 15(2)

Опубликована: Апрель 1, 2025

ABSTRACT The vagus nerve is the body's primary sensory conduit from gut to brain, traditionally viewed as a passive relay for satiety signals. However, emerging evidence reveals far more complex system—one that actively encodes diverse aspects of meal‐related information, mechanical stretch nutrient content, metabolic state, and even microbial metabolites. This review challenges view vagal afferent neurons (VANs) simple meal‐termination sensors highlights their specialized subpopulations, modalities, downstream brain circuits, which shape feeding behavior, metabolism, cognition. We integrate recent advances single‐cell transcriptomics, neural circuit mapping, functional imaging examine how VANs contribute gut–brain communication beyond satiety, including roles in food reward memory formation. By synthesizing latest research highlighting directions field, this provides comprehensive update on pathways role integrators meal information.

Язык: Английский

Процитировано

0
Reduction of opioid withdrawal symptoms and opioid-induced hyperalgesia by subcutaneous sumatriptan reveals central neuromodulation DOI Creative Commons

Alessandra Pistolesi,

Francesco De Cesaris, Daniela Buonvicino

и другие.

Journal of Pain, Год журнала: 2025, Номер unknown, С. 105456 - 105456

Опубликована: Июнь 1, 2025

Язык: Английский

Процитировано

0
Separate anterior paraventricular thalamus projections differentially regulate sensory and affective aspects of pain DOI Creative Commons

Selomon Assefa Mindaye,

Wei‐Hsin Chen,

Shih-Che Lin

и другие.

Cell Reports, Год журнала: 2024, Номер 43(11), С. 114946 - 114946

Опубликована: Ноя. 1, 2024

The experience of pain is complex, involving both sensory and affective components, yet the underlying neural mechanisms remain elusive. Here, we show that formalin-induced behaviors coincide with increased responses in glutamatergic neurons within anterior paraventricular nucleus thalamus (PVA). Furthermore, describe non-overlapping subpopulations PVAVgluT2 involved processing, whose activity varies across different states. Activating PVA sufficient to induce mechanical hypersensitivity aversion behaviors, whereas suppression ameliorates pain. identify segregation

Язык: Английский

Процитировано

2
Tachykinin signaling in the right parabrachial nucleus mediates early-phase neuropathic pain development DOI Creative Commons
Yinxia Li, Ngoc T. Ha, Juan Li

и другие.

Neuron, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

The lateral parabrachial nucleus (PBN) is critically involved in neuropathic pain modulation. However, the cellular and molecular mechanisms underlying this process remain largely unknown. Here, we report that mice, right-sided, but not left-sided, PBN plays an essential role development of hyperalgesia following nerve injury, irrespective injury side. Spino-parabrachial pathways targeting right-sided display short-term facilitation, neurons exhibit increase excitability activity after injury. Inhibiting Tacr1-positive neurons, blocking Tacr1-encoding tachykinin 1 receptor (NK1R), or knocking down Tacr1 gene rather than alleviates pain-induced sensory hypersensitivity. Additionally, a critical during early phase pain. These results highlight NK1R lateralized modulation by PBN, providing new insights into

Язык: Английский

Процитировано

2
The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States DOI Creative Commons
Aman Upadhyay, Mark A. Gradwell, Thomas J. Vajtay

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 23, 2024

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading touch pain, known mechanical allodynia. Two main drivers peripheral information, mechanoreceptors (LTMRs) postsynaptic dorsal column neurons (PSDCs), terminate in brainstem nuclei (DCN). Activity within DRG, spinal cord, DCN have all been implicated mediating allodynia, yet remains understudied at cellular, circuit, functional levels compared other two. Here, we show that gracile nucleus (Gr) mediates sensitivity for contributes allodynia during neuropathic pain mice. We found Gr contains local inhibitory interneurons addition thalamus-projecting neurons, which are differentially innervated by primary afferents inputs. Functional manipulations these distinct neuronal populations resulted bidirectional changes sensitivity, but did not affect noxious or thermal sensitivity. silencing projection activating was able reduce hypersensitivity, enhancing inhibition ameliorate paw withdrawal signatures like shaking. Collectively, results suggest plays a specific role hypersensitivity low-threshold, innocuous activity affective, pain-associated phenotypes Therefore, circuits work tandem with traditional underlying resulting enhanced signaling brain pain.

Язык: Английский

Процитировано

1