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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., 2016). 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
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...
February 16, 2017: Gene Therapy
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
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...
February 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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...
January 11, 2017: Neuroscience
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
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
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
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
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
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
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
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
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
A B Ribeiro, P C G de Barcellos-Filho, C R Franci, L Menescal-de-Oliveira, R S Saia
AIM: Sepsis has been associated with acute behavioural changes in humans and rodents, which consists of a motivational state and an adaptive response that improve survival. However, the involvement of peripheral cytokines synthesized during systemic inflammation as modulators of the tonic immobility (TI) defensive behaviour remains a literature gap. Our purposes were to characterize the TI defensive behaviour in endotoxemia guinea-pigs at acute phase and after recovery from the initial inflammatory challenge...
October 2016: Acta Physiologica
Neda Assareh, Mahsa Sarrami, Pascal Carrive, Gavan P McNally
Rodents display characteristic defense responses to predators that are influenced by predatory imminence. The midbrain periaqueductal gray (PAG) serves an important role controlling these responses. The most influential model states that variations in defensive topography are due to distinct PAG regions: ventrolateral PAG (VLPAG) controls postencounter defense, such as freezing and immobility, whereas lateral PAG (LPAG) controls circa-strike defense, such as escape and flight. Here we used channel rhodopsin (ChR2) stimulation to probe the structure of defensive behavior controlled by LPAG and VLPAG...
August 2016: Behavioral Neuroscience
Ning Wang, Ting Zhang, Yuan-Lin Su, Jin-Yan Wang, Fei Luo
Deep brain stimulation (DBS) is a surgical treatment which has shown remarkable therapeutic benefits for patients with a variety of neurologic conditions. As an important application, DBS has been used to treat intractable pain for over 60 years. Clinical studies have revealed that the selection of the stimulation sites depended on the types of pain. In this study, we selected ventrolateral periaqueductal gray (vlPAG) and ventral posterior lateral nucleus (VPL) as the target brain areas, which were widely used in clinical treatment of refractory pain, to clarify and compare the effects of vlPAG and VPL stimulation on different models of pain...
April 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
William R Millington, M Sertac Yilmaz, Carlos Feleder
This study tested the hypothesis that the initial fall in arterial pressure evoked by lipopolysaccharide (LPS) is mediated by the ventrolateral column of the midbrain periaqueductal gray region (vlPAG). To test this hypothesis, the local anaesthetic lidocaine (2%; 0.1 μL, 0.2 μL or 1.0 μL), the delta opioid receptor antagonist naltrindole (2 nmol) or saline was microinjected into the vlPAG of isoflurane-anaesthetized rats bilaterally and LPS (1 mg/kg) or saline was administered intravenously 2 min later...
June 2016: Clinical and Experimental Pharmacology & Physiology
Olivia K Faull, Mark Jenkinson, Martyn Ezra, Kyle Ts Pattinson
The sensation of breathlessness is the most threatening symptom of respiratory disease. The different subdivisions of the midbrain periaqueductal gray (PAG) are intricately (and differentially) involved in integrating behavioural responses to threat in animals, while the PAG has previously only been considered as a single entity in human research. Here we investigate how these individual PAG columns are differently involved with respiratory threat. Eighteen healthy subjects were conditioned to associate shapes with certain or uncertain impending respiratory load, and scanned the following day during anticipation and application of inspiratory loading using 7 T functional MRI...
February 27, 2016: ELife
Hsin-Jung Lee, Lu-Yang Chang, Yu-Cheng Ho, Shu-Fang Teng, Ling-Ling Hwang, Ken Mackie, Lih-Chu Chiou
The orexin system consists of orexin A/hypocretin 1 and orexin B/hypocretin 2, and OX1 and OX2 receptors. Our previous electrophysiological study showed that orexin A in the rat ventrolateral periaqueductal gray (vlPAG) induced antinociception via an OX1 receptor-initiated and endocannabinoid-mediated disinhibition mechanism. Here, we further characterized antinociceptive effects of orexins in the mouse vlPAG and investigated whether this mechanism in the vlPAG can contribute to stress-induced analgesia (SIA) in mice...
June 2016: Neuropharmacology
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