The differential role of specific POMC neuronal circuits in mediating the beneficial and detrimental effects of opioids.
特定 POMC 神经元回路在调节阿片类药物的有益和有害作用中的不同作用。
基本信息
- 批准号:MR/P025749/1
- 负责人:
- 金额:$ 40.06万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Morphine-like drugs (opioids) have been used and abused for centuries, mainly for their pain-relieving and rewarding effects. These drugs still remain important treatments for pain, however, they have multiple undesirable side-effects which greatly limit their clinical usefulness. These include sedation, suppression of breathing and rewarding effects which can lead to addiction.Morphine-like drugs work by mimicking the action of chemicals made naturally in the body, called endogenous opioids. The best known of these is beta-endorphin and it has an important role in regulating the pain we experience - especially when we are under stress it can be released to suppress pain perception. This natural release of beta-endorphin does not cause the side effects that are seen with opioid drugs like morphine. This may give us a clue as to how to achieve better pain relief that has reduced side effects.A first step towards this goal is to better understand the function of the brain circuits that release endogenous opioids. This has previously been difficult as beta-endorphin is made in only two small, inaccessible groups of neurons in the brain. However, by using selective genetic engineering techniques we can introduce modified receptors (DREADDs) into the beta-endorphin releasing neurons of genetically engineered mice. This allows us to selectively activate (or inhibit) these neurons by giving an otherwise inactive drug and study the effects on animal behaviour.We will test whether the beta-endorphin neurons in the brainstem can produce an analgesic effect; assess whether this is of use in models of chronic pain and also whether this more natural way of releasing opioids exerts a pain relieving effect that is associated with fewer side effects (we believe that there may be reduced sedation, reward and addictive potential). We will also determine whether the pain relief from stress, feeding and vagal nerve stimulation are produced by the activation of these brainstem beta-endorphin producing neurons.
吗啡类药物(阿片类药物)已经被使用和滥用了几个世纪,主要是因为它们的止痛和奖励作用。这些药物仍然是疼痛的重要治疗方法,然而,它们具有多种不良副作用,这极大地限制了它们的临床用途。吗啡类药物通过模仿体内自然产生的化学物质(称为内源性阿片类药物)的作用来发挥作用。其中最著名的是β-内啡肽,它在调节我们所经历的疼痛方面起着重要作用-特别是当我们处于压力之下时,它可以被释放以抑制疼痛感知。这种β-内啡肽的自然释放不会引起吗啡等阿片类药物的副作用。这可能会给我们一个线索,如何实现更好的疼痛缓解,减少副作用。实现这一目标的第一步是更好地了解释放内源性阿片类药物的大脑回路的功能。这在以前是很困难的,因为β-内啡肽只在大脑中两个小的、难以接近的神经元群中产生。然而,通过使用选择性基因工程技术,我们可以将修饰的受体(DREADD)引入基因工程小鼠的β-内啡肽释放神经元中。这使得我们能够有选择地激活我们将测试脑干中的β-内啡肽神经元是否能产生镇痛作用;评估这是否适用于慢性疼痛模型,以及这种释放阿片类药物的更自然方式是否具有与较少副作用相关的疼痛缓解作用(我们认为可能会降低镇静、奖励和成瘾潜力)。我们还将确定压力、进食和迷走神经刺激引起的疼痛缓解是否是通过激活这些脑干β-内啡肽产生神经元产生的。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hedonic drinking engages a supraspinal inhibition of thermal nociception in adult rats
- DOI:10.1097/j.pain.0000000000001482
- 发表时间:2019-05-01
- 期刊:
- 影响因子:7.4
- 作者:Davies, Alexander J.;Kim, Doyun;Oh, Seog Bae
- 通讯作者:Oh, Seog Bae
Neurons in the Dorsomedial Hypothalamus Promote, Prolong, and Deepen Torpor in the Mouse.
- DOI:10.1523/jneurosci.2102-21.2022
- 发表时间:2022-05-25
- 期刊:
- 影响因子:5.3
- 作者:Ambler, Michael;Hitrec, Timna;Wilson, Andrew;Cerri, Matteo;Pickering, Anthony
- 通讯作者:Pickering, Anthony
Pro-opiomelanocortin neurons in the nucleus of the solitary tract mediate endorphinergic endogenous analgesia in mice.
- DOI:10.1097/j.pain.0000000000002802
- 发表时间:2022-10
- 期刊:
- 影响因子:7.4
- 作者:P. H. Patra;Becks Tench;T. Hitrec;F. Holmes;R. Drake;S. Cerritelli;D. Spanswick;A. Pickering
- 通讯作者:P. H. Patra;Becks Tench;T. Hitrec;F. Holmes;R. Drake;S. Cerritelli;D. Spanswick;A. Pickering
Release of beta-endorphin from brainstem POMC neurons in mice is anxiolytic but not rewarding
小鼠脑干 POMC 神经元释放 β-内啡肽具有抗焦虑作用,但无益处
- DOI:
- 发表时间:2018
- 期刊:
- 影响因子:0
- 作者:Fiona Holmes
- 通讯作者:Fiona Holmes
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Anthony Pickering其他文献
IPEADAM study: Exposure to Der p 1, endotoxin and damp in asthmatic children and healthy controls
- DOI:
10.1016/s0091-6749(02)81232-5 - 发表时间:
2002-01-01 - 期刊:
- 影响因子:
- 作者:
Gillian Fletcher;Gael Tavernier;Helen Francis;Lesley Oldham;Angela Fletcher;Peter Frank;Anthony Pickering;Robert Niven - 通讯作者:
Robert Niven
PD19-07 CRH NEURONS OF BARRINGTON’S NUCLEUS ARE NECESSARY BUT NOT SUFFICIENT FOR CO-ORDINATED VOIDING IN MICE
- DOI:
10.1016/j.juro.2018.02.997 - 发表时间:
2018-04-01 - 期刊:
- 影响因子:
- 作者:
Hiroki Ito;Marcus Drake;Christopher Fry;Anthony Kanai;Anthony Pickering - 通讯作者:
Anthony Pickering
Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin–angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial
非心脏手术中术前 N 端 B 型利钠肽前体与停止或继续使用肾素-血管紧张素系统抑制剂后的心肌损伤:一项 2 期随机对照多中心试验的预设分析
- DOI:
10.1016/j.bja.2024.01.010 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
A. Gutierrez del Arroyo;Akshaykumar Patel;T. E. Abbott;Salma Begum;P. Dias;S. Somanath;Alexander Middleditch;Stuart Cleland;David Brealey;R. Pearse;G. Ackland;G. Ackland;Tim Martin;Maria Fernandez;F. Seidu;M. Pakats;Otto Mahr;N. Macdonald;Filipa Dos Santos;Amaia Arrieta Garcia;R. Uddin;R. Pearse;Emily Subhedar;Yize Wan;Akshaykumar Patel;T. Shahid;M. Gooneratne;Charlotte Trainer;Bethan Griffiths;Steven Dunkley;S. May;Sophie Walker;Alexander Fowler;Timothy Stephens;Monica Oliveira;M. Januszewska;E. Niebrzegowska;Vanessa Amaral;J. Kassam;Sophie Young;Shanaz Ahmad;J. Whalley;Ryan W. Haines;S. Hui;Rob Hammond;David R Crane;David Brealey;S. Bampoe;Robert Stephens;A. Reyes;G. Martir;Chimverly Diaz;G. Minto;Natasha Wilmshurst;Debbie;Tracy Ward;Gavin Werrett;Susan Cummins;Alan Amber;A. Biffen;Stephen Boumphrey;Elizabeth Cann;Charlotte Eglinton;Elaine Jones;M. Mwadeyi;S. Piesley;Richard A Cowan;Julie Alderton;Fiona Reed;Joanne Smith;Amy Turner;L. Madziva;Abigail Patrick;Penny Harris;Harry Lang;Alexander Middleditch;Anthony Pickering;C. O’Donovan;R. Houlihan;Rosina Jarvis;A. Shrimpton;T. Farmery;Katy Tucker;Danielle Davis;Sameer Somanth;Louise Duncan;H. Melsom;Sarah Clark;M. Kent;Michelle Wood;Ami Laidlaw;Tracy Matheson;K. Potts;A. Kay;Stefanie Hobson;John Sear;V. Kapil;A. Archbold;Matt Wilson;Drilona Dndrejaj;Dennis Ly - 通讯作者:
Dennis Ly
Effect of temperature and storage on endotoxin detection in domestic dust samples
- DOI:
10.1016/s0091-6749(02)81432-4 - 发表时间:
2002-01-01 - 期刊:
- 影响因子:
- 作者:
Gael Tavernier;Gillian Fletcher;Robert Niven;Anthony Pickering - 通讯作者:
Anthony Pickering
Early Intravenous Beta-Blockade with Esmolol in Adults with Severe Traumatic Brain Injury (EBB-TBI): Protocol for a Phase 2a Intervention Design Study
成人严重创伤性脑损伤 (EBB-TBI) 早期静脉注射艾司洛尔β-阻断:2a 期干预设计研究方案
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:3.5
- 作者:
M. Thomas;Katia Hayes;Paul White;Aravind Ramesh;L. Culliford;G. Ackland;Anthony Pickering - 通讯作者:
Anthony Pickering
Anthony Pickering的其他文献
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{{ truncateString('Anthony Pickering', 18)}}的其他基金
SenseCheQ: Community-based sensory testing for early identification of Chemotherapy Induced Peripheral Neuropathy.
SenseCheQ:基于社区的感觉测试,用于早期识别化疗引起的周围神经病变。
- 批准号:
MR/W027925/1 - 财政年份:2022
- 资助金额:
$ 40.06万 - 项目类别:
Research Grant
Chilling time with synthetic torpor
合成麻木的冷却时间
- 批准号:
BB/W007266/1 - 财政年份:2022
- 资助金额:
$ 40.06万 - 项目类别:
Research Grant
Targeting torpor circuits across species: towards translation
针对跨物种的麻木回路:走向翻译
- 批准号:
MR/W029138/1 - 财政年份:2022
- 资助金额:
$ 40.06万 - 项目类别:
Research Grant
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