Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 1, 2024

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to brain where they relay sensory information body. The existence and function of a substantial axon collateral network, also arising PNs remaining within cord, is less well appreciated. Here we use retrograde viral transduction strategy characterise novel subpopulation deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed virally labelled PN cell bodies formed discrete column lateral part Lamina V (LV

Язык: Английский

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Neuroanatomy of the nociceptive system: From nociceptors to brain networks

International review of neurobiology, Год журнала: 2024, Номер unknown, С. 1 - 39

Опубликована: Янв. 1, 2024

Язык: Английский

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Descending GABAergic Neurons of the RVM That Mediate Widespread Bilateral Antinociception

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 29, 2023

Summary Neurons projecting from the rostral ventromedial medulla (RVM) to spinal dorsal horn are critical elements of endogenous pain control systems. Here, we describe a GABA/glycinergic pathway that predominantly innervates superficial horn. Anatomical and optogenetic tracing these neurons single unilateral site lumbar cord indicated give rise dense bilateral innervation along its entire rostrocaudal axis. Chemogenetic activation caused widespread reduction in heat, cold, mechanical sensitivity, while their silencing with tetanus toxin induced allodynia spontaneous pain-like aversive behaviors. Consistent continuous role prevention pain, many descending RVM GABAergic were found be tonically active. This may therefore relevant for conditioned analgesia, dysfunction underlie chronic syndromes.

Язык: Английский

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Modulating Neural Circuits of Pain in Preclinical Models: Recent Insights for Future Therapeutics

Cells, Год журнала: 2024, Номер 13(12), С. 997 - 997

Опубликована: Июнь 7, 2024

Chronic pain is a pathological state defined as daily sensation over three consecutive months. It affects up to 30% of the general population. Although significant research efforts have been made in past 30 years, only few and relatively low effective molecules emerged treat chronic pain, with considerable translational failure rate. Most preclinical models focused on sensory neurotransmission, particular emphasis dorsal horn spinal cord first relay nociceptive information. Beyond impaired transmission, also accompanied by numerous comorbidities, such anxiety-depressive disorders, anhedonia motor cognitive deficits gathered under term "pain matrix". The emergence cutting-edge techniques assessing specific neuronal circuits allow in-depth studies connections between matrix" behavioural outputs. Pain behaviours are assessed not reflex-induced responses but various or more complex order obtain most complete picture an animal's state. This review summarises latest findings modulation brain component matrix proposes new opportunities unravel mechanisms pain.

Язык: Английский

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Central mechanisms of muscle tone regulation: implications for pain and performance

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Дек. 9, 2024

Muscle tone represents a foundational property of the motor system with potential to impact musculoskeletal pain and performance. is involuntary, dynamically adaptive, interconnected across body, sensitive postural demands, distinct from voluntary control. Research has historically focused on pathological tone, peripheral regulation, contributions passive tissues, without consideration neural regulation active its consequences, particularly for neurologically healthy individuals. Indeed, simplistic models based stretch reflex, which neglect central are still perpetuated today. Recent advances regarding dispersed different literatures, including animal physiology, science, control, neurology, child development. This paper brings together diverse areas research construct conceptual model neuroscience underlying muscle tone. It highlights how multiple tonic drive networks tune excitability complex spinal feedback circuits in concert various sources sensory relation gravity, arousal levels. The also reveals activity disrupted people disorders can lead marked impairment. presents evidence that integrative somatic methods address discusses mechanisms implications rehabilitation improve

Язык: Английский

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Select terpenes from Cannabis sativa are antinociceptive in mouse models of post-operative pain and fibromyalgia via adenosine A2a receptors

Pharmacological Reports, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Язык: Английский

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Effects of stress contagion on anxiogenic‐ and orofacial inflammatory pain‐like behaviors with brain activation in mice

European Journal Of Oral Sciences, Год журнала: 2023, Номер 131(4)

Опубликована: Июнь 28, 2023

Abstract The conditions of stress contagion are induced in bystanders without direct experiences stressful events. This study determined the effects on masseter muscle nociception mice. Stress was developed after cohabitating with a conspecific mouse subjected to social defeat for 10 days. On Day 11, increased anxiety‐ and orofacial inflammatory pain‐like behaviors. c‐Fos FosB immunoreactivities evoked by stimulation were upper cervical spinal cord, while expressions rostral ventromedial medulla, including lateral paragigantocellular reticular nucleus raphe magnus level serotonin medulla under contagion, number positive cells nucleus. anterior cingulate cortex insular cortex, both which positively correlated brain‐derived neurotrophic factor contagion. These results indicate that can cause neural changes brain, resulting nociception, as seen

Язык: Английский

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Postcolitis Alterations in Nociceptive Properties of Neurons in the Rat Nucleus Raphe Magnus and Dorsal Raphe Nucleus

Journal of Evolutionary Biochemistry and Physiology, Год журнала: 2023, Номер 59(4), С. 1057 - 1076

Опубликована: Июль 1, 2023

Язык: Английский

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Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 10, 2023

The supraspinal descending pain modulatory system (DPMS) shapes perception via monoaminergic modulation of sensory information in the spinal cord. However, role and synaptic mechanisms noradrenergic signaling remain unclear. Here, we establish that neurons locus coeruleus (LC) are essential for opioid antinociception. Unexpectedly, given prior emphasis on serotonergic pathways, find antinociception is primarily driven by excitatory output from ventrolateral periaqueductal gray (vlPAG) to LC. Furthermore, identify a previously unknown opioid-sensitive inhibitory input rostroventromedial medulla (RVM), suppression which disinhibits LC drive We also report presence prominent bifurcating outputs vlPAG RVM. Our findings significantly revise current models DPMS novel antinociceptive pathway may contribute multiple forms modulation.

Язык: Английский

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Elevated Serotonin in Mouse Spinal Dorsal Horn Is Pronociceptive

eNeuro, Год журнала: 2023, Номер 10(12), С. ENEURO.0293 - 23.2023

Опубликована: Ноя. 9, 2023

Abstract Serotonergic neurons in the rostral ventral medulla (RVM) contribute to bidirectional control of pain through modulation spinal and trigeminal nociceptive networks. Deficits this pathway are believed pathologic states, but whether changes serotonergic mechanisms pro- or antinociceptive is debated. We used a combination optogenetics fiber photometry examine these more closely. find that optogenetic activation RVM afferents cord naive mice produces mechanical hypersensitivity conditioned place aversion (CPA). Neuropathic pain, produced by chronic constriction injury infraorbital nerve (CCI-ION), evoked tonic increase serotonin (5HT) concentrations within nucleus caudalis (SpVc), measured with liquid chromatography-tandem mass spectroscopy (LC-MS/MS). By contract, CCI-ION had no effect on phasic transients SpVc, noxious pinch, sensor. These findings suggest release pronociceptive an sustained signaling, rather than event driven increases, potentiate nociception models pain.

Язык: Английский

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