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Periaqueductal gray

Neil C Ford, Mark L Baccei
Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life...
October 14, 2016: Neuroscience
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
S Aybek, P Vuilleumier
Brain imaging techniques provide unprecedented opportunities to study the neural mechanisms underlying functional neurologic disorder (FND, or conversion disorder), which have long remained a mystery and clinical challenge for physicians, as they arise with no apparent underlying organic disease. One of the first questions addressed by imaging studies concerned whether motor conversion deficits (e.g., hysteric paralysis) represent a form of (perhaps unconscious) simulation, a mere absence of voluntary movement, or more specific disturbances in motor control (such as abnormal inhibition)...
2017: Handbook of Clinical Neurology
Sophie Kobuch, Azharuddin Fazalbhoy, Rachael Brown, Luke A Henderson, Vaughan G Macefield
Experimentally induced tonic muscle pain evokes divergent muscle vasoconstrictor responses, with some individuals exhibiting a sustained increase in muscle sympathetic nerve activity (MSNA), and others a sustained decrease. These patterns cannot be predicted from an individual's baseline physiological or psychological measures. The aim of this study was to investigate whether the different muscle sympathetic responses to tonic muscle pain were associated with differential changes in regional brain activity...
October 3, 2016: Human Brain Mapping
Suku-Maran Shalini, Deron R Herr, Wei-Yi Ong
Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception...
October 1, 2016: Molecular Neurobiology
Andrew A Nicholson, Tomas Ros, Paul A Frewen, Maria Densmore, Jean Théberge, Rosemarie C Kluetsch, Rakesh Jetly, Ruth A Lanius
OBJECTIVE: Electroencephalogram (EEG) neurofeedback aimed at reducing the amplitude of the alpha-rhythm has been shown to alter neural networks associated with posttraumatic stress disorder (PTSD), leading to symptom alleviation. Critically, the amygdala is thought to be one of the central brain regions mediating PTSD symptoms. In the current study, we compare directly patterns of amygdala complex connectivity using fMRI, before and after EEG neurofeedback, in order to observe subcortical mechanisms associated with behavioural and alpha oscillatory changes among patients...
2016: NeuroImage: Clinical
Janine Thome, Maria Densmore, Paul A Frewen, Margaret C McKinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius
OBJECTIVES: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest...
September 20, 2016: Human Brain Mapping
Junko Kono, Kohtarou Konno, Ashraf Hossain Talukder, Toshimitsu Fuse, Manabu Abe, Katsuya Uchida, Shuhei Horio, Kenji Sakimura, Masahiko Watanabe, Keiichi Itoi
We examined the morphological features of corticotropin-releasing factor (CRF) neurons in a mouse line in which modified yellow fluorescent protein (Venus) was expressed under the CRF promoter. We previously generated the CRF-Venus knock-in mouse, in which Venus is inserted into the CRF gene locus by homologous recombination. In the present study, the neomycin phosphotransferase gene (Neo), driven by the pgk-1 promoter, was deleted from the CRF-Venus mouse genome, and a CRF-Venus∆Neo mouse was generated. Venus expression is much more prominent in the CRF-Venus∆Neo mouse when compared to the CRF-Venus mouse...
September 16, 2016: Brain Structure & Function
R A R Drake, J L Leith, F Almahasneh, J Martindale, A W Wilson, B Lumb, L F Donaldson
UNLABELLED: Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase-prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown...
August 31, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Haruka Takeshige, Yuji Ueno, Koji Kamagata, Fuyuko Sasaki, Kazuo Yamashiro, Ryota Tanaka, Shigeki Aoki, Nobutaka Hattori
BACKGROUND: Midbrain infarction shows diverse patterns of ophthalmoplegia; however, the association of ophthalmoplegia with a precise microanatomy has not been fully studied. Here, we report a patient with characteristic ophthalmoplegia and explore the associated pathologic fiber tracts using diffusion-tensor imaging (DTI). METHODS: A 21-year-old woman with an 11-year history of mixed connective tissue disease (MCTD) abruptly developed bilateral internuclear ophthalmoplegia (INO) with upward gaze and convergence palsies...
August 24, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Kyle N Campion, Kimber A Saville, Michael M Morgan
The dorsal raphe nucleus (DRN) is embedded in the ventral part of the caudal periaqueductal gray (PAG). Electrical or chemical activation of neurons throughout this region produces antinociception. The objective of this manuscript is to determine whether the ventrolateral PAG and DRN are distinct antinociceptive systems. This hypothesis was tested by determining the antinociceptive potency of microinjecting morphine into each structure (Experiment 1), creating a map of effective microinjection sites that produce antinociception (Experiment 2), and comparing the development of antinociceptive tolerance to repeated microinjections of morphine into the ventrolateral PAG and DRN (Experiment 3)...
August 26, 2016: European Journal of Neuroscience
Hugh Sims-Williams, Julian C Matthews, Peter S Talbot, Sarah Love-Jones, Jonathan Cw Brooks, Nikunj K Patel, Anthony E Pickering
Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [(11)C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or anaesthesia dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [(11)C]DPN and [(15)O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation...
August 20, 2016: NeuroImage
Fei Liu, Jing Ma, Peng Liu, Zheng Chu, Gang Lei, Xiao-di Jia, Jia-Bei Wang, Yong-Hui Dang
INTRODUCTION: Previous studies have indicated a possible role of histidine triad nucleotide-binding protein 1 (HINT1) on sustaining the regulatory crosstalk of N-methyl-D-aspartate acid glutamate receptors (NMDARs) and G-protein-coupled receptors (GPCRs) such as the μ-opioid receptor (MOR). Both receptors are present in the midbrain periaqueductal gray neurons, an area that plays a central role in the supraspinal antinociceptive process. METHODS: In the present study, a battery of pain-related behavioral experiments was applied to Hint1 knockout, heterozygous and wild-type mice...
August 2016: Brain and Behavior
Valerie L Tryon, Sheri J Y Mizumori, Michael M Morgan
Microinjection of morphine into the periaqueductal gray (PAG) produces antinociception. In vitro slice recordings indicate that all PAG neurons are sensitive to morphine either by direct inhibition or indirect disinhibition. We tested the hypothesis that all PAG neurons respond to opioids in vivo by examining the extracellular activity of PAG neurons recorded in lightly anesthetized and awake rats. Spontaneous activity was less than 1Hz in most neurons. Noxious stimuli (heat, pinch) caused an increase in activity in 57% and 75% of the neurons recorded in anesthetized and awake rats, respectively...
October 29, 2016: Neuroscience
Juliette Viellard, Marcus Vinicius C Baldo, Newton Sabino Canteras
Previous studies from our group have shown that risk assessment behaviors are the primary contextual fear responses to predatory and social threats, whereas freezing is the main contextual fear response to physically harmful events. To test contextual fear responses to a predator or aggressive conspecific threat, we developed a model that involves placing the animal in an apparatus where it can avoid the threat-associated environment. Conversely, in studies that use shock-based fear conditioning, the animals are usually confined inside the conditioning chamber during the contextual fear test...
December 15, 2016: Behavioural Brain Research
Shane B Johnson, Eric B Emmons, Rachel M Anderson, Ryan M Glanz, Sara A Romig-Martin, Nandakumar S Narayanan, Ryan T LaLumiere, Jason J Radley
UNLABELLED: The bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH). Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure. Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress...
August 17, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Rimenez R Souza, Antonio P Carobrez
The dorsolateral region of the midbrain periaqueductal gray (dlPAG) modulates both innate and conditioned fear responses. However, the contribution of the rostrocaudal portions of the dlPAG to defense reactions and aversive memories remains unclear. Here, we sought to investigate the effects of N-methyl-d-aspartate (NMDA) receptor blockade within rostral or caudal dlPAG of rats exposed to innate and learned fear to cat odor. For this, adult male Wistar rats were microinjected with the NMDA antagonist D-2-amino-5-phosphono-pentanoate (AP5; 3 or 6nmol/0...
December 15, 2016: Behavioural Brain Research
Xianbo Zhuang, Yanxiu Chen, Xianpeng Zhuang, Tuanzhi Chen, Tao Xing, Weifei Wang, Xiafeng Yang
BACKGROUND/AIMS: Hypersensitive pain response is often observed in patients with Parkinson's disease (PD); however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines (PICs) system of PAG in regulating exaggerated pain evoked by PD...
2016: Frontiers in Neurology
Andrew Chih Wei Huang, Hsiang-Chin Lu, Bai Chuang Shyu
Approximately 8% of stroke patients present symptoms of central post-stroke pain (CPSP). CPSP is associated with allodynia and hypersensitivity to nociceptive stimuli. Although some studies have shown that neuropathic pain may involve the dorsolateral prefrontal cortex, rostral anterior cingulate cortex, amygdala, hippocampus, periaqueductal gray, rostral ventromedial medulla, and medial thalamus, the neural substrates and their connections that mediate CPSP remain unclear. [(14)C]-Iodoantipyrine (IAP) uptake can be measured to evaluate spontaneously active pain...
2016: Journal of Visualized Experiments: JoVE
Lori N Eidson, Kiyoshi Inoue, Larry J Young, Malu G Tansey, Anne Z Murphy
Opioid tolerance and the potential for addiction is a significant burden associated with pain management, yet its precise underlying mechanism and prevention remain elusive. Immune signaling contributes to the decreased efficacy of opioids, and we recently demonstrated that toll-like receptor 4 (TLR4)-mediated neuroinflammation in the periaqueductal gray (PAG) drives tolerance. Tumor necrosis factor (TNF), a product of TLR4 signaling, promotes inflammation and facilitates glutamatergic signaling, key components of opioid tolerance...
July 27, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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