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https://www.readbyqxmd.com/read/28374016/divergent-modulation-of-nociception-by-glutamatergic-and-gabaergic-neuronal-subpopulations-in-the-periaqueductal-gray
#1
Vijay K Samineni, Jose G Grajales-Reyes, Bryan A Copits, Daniel E O'Brien, Sarah L Trigg, Adrian M Gomez, Michael R Bruchas, Robert W Gereau
The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28367595/ionic-currents-influencing-spontaneous-firing-and-pacemaker-frequency-in-dopamine-neurons-of-the-ventrolateral-periaqueductal-gray-and-dorsal-raphe-nucleus-vlpag-drn-a-voltage-clamp-and-computational-modelling-study
#2
Antonios G Dougalis, Gillian A C Matthews, Birgit Liss, Mark A Ungless
Dopamine (DA) neurons of the ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) fire spontaneous action potentials (APs) at slow, regular patterns in vitro but a detailed account of their intrinsic membrane properties responsible for spontaneous firing is currently lacking. To resolve this, we performed a voltage-clamp electrophysiological study in brain slices to describe their major ionic currents and then constructed a computer model and used simulations to understand the mechanisms behind autorhythmicity in silico...
April 3, 2017: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/28328571/neuropathic-pain-induced-enhancement-of-spontaneous-and-pain-evoked-neuronal-activity-in-the-periaqueductal-gray-that-is-attenuated-by-gabapentin
#3
Vijay K Samineni, Louis S Premkumar, Carl L Faingold
Neuropathic pain is a debilitating pathological condition that is poorly understood. Recent evidence suggests that abnormal central processing occurs during the development of neuropathic pain induced by the cancer chemotherapeutic agent, paclitaxel. Yet, it is unclear what role neurons in supraspinal pain network sites, such as the periaqueductal gray, play in altered behavioral sensitivity seen during chronic pain conditions. To elucidate these mechanisms, we studied the spontaneous and thermally evoked firing patterns of ventrolateral periaqueductal gray (vlPAG) neurons in awake-behaving rats treated with paclitaxel to induce neuropathic pain...
March 21, 2017: Pain
https://www.readbyqxmd.com/read/28321594/disrupted-functional-connectivity-of-periaqueductal-gray-subregions-in-episodic-migraine
#4
Zhiye Chen, Xiaoyan Chen, Mengqi Liu, Shuangfeng Liu, Lin Ma, Shengyuan Yu
BACKGROUND: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the altered dysfunction of PAG subregions were not totally detected up to now. The aim of this study is to investigate the altered functional connectivity of PAG subregions in EM patients. METHODS: The brain structural images and resting state functional MR imaging (rs-fMRI) data were obtained from 18 normal controls (NC) and 18 EM patients on 3.0 T MR system. Seven subregions of PAG were classified as bilateral ventrolateral PAG (vlPAG), lateral PAG (lPAG), dorsolateral PAG (dlPAG) and dorsomedial PAG (dmPAG)...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28306133/injection-of-toll-like-receptor-4-sirna-into-the-ventrolateral-periaqueductal-gray-attenuates-withdrawal-syndrome-in-morphine-dependent-rats
#5
Q F Liu, L Li, Y Q Guo, X Li, Z D Mou, X Wang, G Z Du
We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed...
December 1, 2016: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28274653/effects-of-chemical-stimulation-of-the-lateral-wings-of-the-dorsal-raphe-nucleus-on-panic-like-defensive-behaviors-and-fos-protein-expression-in-rats
#6
Melina Matthiesen, Ailton Spiacci, Hélio Zangrossi
The lateral wings subnucleus of the dorsal raphe nucleus (lwDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the lwDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the lwDR with kainic acid...
March 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28211789/the-cortical-connectivity-of-the-periaqueductal-gray-and-the-conditioned-response-to-the-threat-of-breathlessness
#7
Olivia K Faull, Kyle Ts Pattinson
Previously we observed differential activation in individual columns of the periaqueductal grey (PAG) during breathlessness and its conditioned anticipation (Faull et al., 2016b). Here, we have extended this work by determining how the individual columns of the PAG interact with higher cortical centres, both at rest and in the context of breathlessness threat. Activation was observed in ventrolateral PAG (vlPAG) and lateral PAG (lPAG), where activity scaled with breathlessness intensity ratings, revealing a potential interface between sensation and cognition during breathlessness...
February 17, 2017: ELife
https://www.readbyqxmd.com/read/28206989/il-4-mediated-by-hsv-vector-suppresses-morphine-withdrawal-response-and-decreases-tnf%C3%AE-nr2b-and-pc-ebp%C3%AE-in-the-periaqueductal-gray-in-rats
#8
H Yi, T Iida, S Liu, D Ikegami, Q Liu, A Iida, D A Lubarsky, S Hao
Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines...
April 2017: Gene Therapy
https://www.readbyqxmd.com/read/28183259/targeting-melatonin-mt2-receptors-a-novel-pharmacological-avenue-for-inflammatory-and-neuropathic-pain
#9
Luca Posa, Danilo De Gregorio, Gabriella Gobbi, Stefano Comai
Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G-protein coupled receptors, MT1 and MT2. In this review, we present the analgesic properties of MLT in preclinical and clinical studies, giving particular emphasis to the effects mediated by MT2 receptors and to recent investigations demonstrating the analgesic effects of MT2 receptor partial agonists in chronic and acute/inflammatory pain conditions. MT2 receptors are localized in specific brain areas, including the reticular and the ventromedial nuclei of the thalamus (part of the ascending nociceptive pathway) and the ventrolateral periaqueductal grey matter (vlPAG) (part of the descending antinociceptive pathway)...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28179123/spinal-or-supraspinal-phosphorylation-deficiency-at-the-mor-c-terminus-does-not-affect-morphine-tolerance-in-vivo
#10
Cherkaouia Kibaly, Hong-Yiou Lin, Horace H Loh, Ping-Yee Law
The development of tolerance to morphine, one of the most potent analgesics, in the management of chronic pain is a significant clinical problem and its mechanisms are poorly understood. Morphine exerts its pharmacological effects via the μ-opioid receptor (MOR). Tolerance is highly connected to G-protein-coupled receptors (GPCR) phosphorylation and desensitization increase. Because morphine desensitization previously has been shown to be MOR phosphorylation- and ß-arrestin2-independent (in contrast to agonists such as fentanyl), we examined the contribution of phosphorylation of the entire C-terminus to the development of antinociceptive tolerance to the partial (morphine) and full (fentanyl) MOR agonists in vivo...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28087339/differential-behavioral-sensitivity-to-carbon-dioxide-co2-inhalation-in-rats
#11
Andrew Winter, Rebecca Ahlbrand, Devanshi Naik, Renu Sah
Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats...
March 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/27906750/role-of-orexin-2-and-cb1-receptors-within-the-periaqueductal-gray-matter-in-lateral-hypothalamic-induced-antinociception-in-rats
#12
Mohammad-Hossein Esmaeili, Zahra Reisi, Somayeh Ezzatpanah, Abbas Haghparast
Orexin plays an important role in pain modulation. Orexin-1 and orexin-2 receptors (Ox1r and Ox2r) are found at high density in the ventrolateral periaqueductal gray matter (vlPAG). Our previous study showed that chemical stimulation of the lateral hypothalamus with carbachol induces antinociception in the tail-flick test, a model of acute pain, and Ox1r-mediated antinociception in the vlPAG is modulated by the activity of vlPAG CB1 receptors. In the current study, TCS OX2 29, an Ox2r antagonist (5, 15, 50, 150, and 500 nmol/l), was microinjected into the vlPAG 5 min before the administration of carbachol (125 nmol/l)...
November 30, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27845162/neuropeptide-glutamic-acid-isoleucine-nei-induced-paradoxical-sleep-in-rats
#13
Moe Fujimoto, Satoru Fukuda, Hidetoshi Sakamoto, Junko Takata, Shigehito Sawamura
Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action...
January 2017: Peptides
https://www.readbyqxmd.com/read/27646556/ventrolateral-periaqueductal-grey-matter-neurotransmission-modulates-cardiac-baroreflex-activity
#14
Davi C Lagatta, Nilson C Ferreira-Junior, Milena Deolindo, Fernando M A Corrêa, Leonardo B M Resstel
Baroreflex activity is a neural mechanism responsible for short-term adjustments in blood pressure (BP). Several supramedullary areas, which send projections to the medulla, are able to control this reflex. In this context, the ventrolateral part of the periaqueductal grey matter (vlPAG), which is a mesencephalic structure, has been suggested to regulate the cardiovascular system. However, its involvement in baroreflex control has never been addressed. Therefore, our hypothesis is that the vlPAG neurotransmission is involved in baroreflex cardiac activity...
December 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27581447/periaqueductal-grey-ep3-receptors-facilitate-spinal-nociception-in-arthritic-secondary-hypersensitivity
#15
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
https://www.readbyqxmd.com/read/27520401/genotype-dependent-responsivity-to-inflammatory-pain-a-role-for-trpv1-in-the-periaqueductal-grey
#16
Manish K Madasu, Bright N Okine, Weredeselam M Olango, Kieran Rea, Róisín Lenihan, Michelle Roche, David P Finn
Negative affective state has a significant impact on pain, and genetic background is an important moderating influence on this interaction. The Wistar-Kyoto (WKY) inbred rat strain exhibits a stress-hyperresponsive, anxiety/depressive-like phenotype and also displays a hyperalgesic response to noxious stimuli. Transient receptor potential subfamily V member 1 (TRPV1) within the midbrain periaqueductal grey (PAG) plays a key role in regulating both aversive and nociceptive behaviour. In the present study, we investigated the role of TRPV1 in the sub-columns of the PAG in formalin-evoked nociceptive behaviour in WKY versus Sprague-Dawley (SD) rats...
August 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27503688/%C3%A2%C2%B51-opioid-receptors-in-the-dorsomedial-and-ventrolateral-columns-of-the-periaqueductal-grey-matter-are-critical-for-the-enhancement-of-post-ictal-antinociception
#17
Renato Leonardo de Freitas, Priscila Medeiros, Asmat Ullah Khan, Norberto Cysne Coimbra
Generalised tonic and tonic-clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ1 -opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post-ictal antinociception. Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA-mediated Cl(-) influx antagonist, was intraperitoneally (IP) administered to induce tonic-clonic seizures in Wistar rats...
December 2016: Synapse
https://www.readbyqxmd.com/read/27429635/analgesic-neural-circuits-are-activated-by-electroacupuncture-at-two-sets-of-acupoints
#18
Man-Li Hu, Zheng-Ying Qiu, Kuang Hu, Ming-Xing Ding
To investigate analgesic neural circuits activated by electroacupuncture (EA) at different sets of acupoints in the brain, goats were stimulated by EA at set of Baihui-Santai acupoints or set of Housanli acupoints for 30 min. The pain threshold was measured using the potassium iontophoresis method. The levels of c-Fos were determined with Streptavidin-Biotin Complex immunohistochemistry. The results showed pain threshold induced by EA at set of Baihui-Santai acupoints was 44.74% ± 4.56% higher than that by EA at set of Housanli acupoints (32...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27335434/role-played-by-periaqueductal-gray-neurons-in-parasympathetically-mediated-fear-bradycardia-in-conscious%C3%A2-rats
#19
Satoshi Koba, Ryo Inoue, Tatsuo Watanabe
Freezing, a characteristic pattern of defensive behavior elicited by fear, is associated with a decrease in the heart rate. Central mechanisms underlying fear bradycardia are poorly understood. The periaqueductal gray (PAG) in the midbrain is known to contribute to autonomic cardiovascular adjustments associated with various emotional behaviors observed during active or passive defense reactions. The purpose of this study was to elucidate the role played by PAG neurons in eliciting fear bradycardia. White noise sound (WNS) exposure at 90 dB induced freezing behavior and elicited bradycardia in conscious rats...
June 2016: Physiological Reports
https://www.readbyqxmd.com/read/27301294/functional-interaction-between-orexin-1-and-cb1-receptors-in-the-periaqueductal-gray-matter-during-antinociception-induced-by-chemical-stimulation-of-the-lateral-hypothalamus-in-rats
#20
M H Esmaeili, Z Reisi, S Ezzatpanah, A Haghparast
BACKGROUND: Chemical stimulation of the lateral hypothalamus (LH) with carbachol induces antinociception which is antagonized by blockade of orexin receptors in some pain modulatory sites in the tail-flick test. In this study, we evaluated the role of orexin-1 and CB1 receptors in the periaqueductal gray matter (PAG), a critical pain modulatory site, in mediation of antinociceptive responses induced by LH stimulation in rats. METHODS: One hundred thirty-two adult male albino Wistar rats weighing 180-250 g were unilaterally implanted with two separate cannulae into the LH and ventrolateral PAG (vlPAG)...
June 15, 2016: European Journal of Pain: EJP
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