Nociceptive input to cerebellar pathways and its behavioural significance

所有的生物都必须面对痛苦——这是一种不愉快的经历，但对于保护动物的福利和最终的生存至关重要。疼痛是一种警告，是你需要做某事的信号。通常你有两个选择：要么离开，以免受重伤；或者，如果你已经受伤了，你只能忍受疼痛。你的大脑会识别出这两种疼痛之间的区别，并做出最佳的身体反应。逃避疼痛意味着动物必须迅速起身离开。它必须跑、跳、飞或游泳来逃离威胁——这是对可逃避的痛苦的积极反应。为了摆脱疼痛，动物必须移动，而移动需要增加肌肉活动。当肌肉在紧急情况下工作时，它们需要增加血压、心率和呼吸，为它们提供额外的氧气和营养。相反，胃痛是无法逃避的。当你移动时，疼痛会一直伴随着你——你所能做的就是忍受它，试着去应对它。这是对无法逃避的痛苦的被动反应。最好的办法是尽量保护受伤的组织，这意味着“躺低”，保持最小的运动——与积极的反应相反。为了有效，对疼痛的主动和被动反应是复杂的，它们需要身体和大脑以高度协调的方式一起工作。对疼痛做出反应的是身体，但协调运动和心肺功能各自变化的是大脑。可以逃避的和无法逃避的疼痛很可能是由大脑中各自独立的连接控制的。我们有充分的证据表明，这是大脑回路控制血压变化的方式，但对大脑回路控制身体运动变化以应对这些不同类型的疼痛所知甚少。目前这项工作的主要目的是找出不同类型的疼痛是否会激活大脑中控制运动的不同回路。我们将特别关注通向小脑的脑回路，小脑是哺乳动物身体运动的主要控制者。我们将绘制大脑内通向小脑的疼痛通路，并找出不可避免的疼痛（如皮肤疼痛）是否激活了不同的疼痛通路，而不可避免的疼痛（如肠道疼痛）是否激活了不同的疼痛通路。此外，通过记录单个脑细胞的电信号，我们将发现疼痛和非疼痛信号是否通过相同的途径发送到小脑。疼痛还会引起压力和焦虑，从而影响动物对疼痛的反应和应对方式。压力会激活大脑的某些部分，改变传入的疼痛信号，从而改变动物对疼痛的反应。我们研究的最后一部分将观察“压力和焦虑”大脑中心是否能改变通向小脑的疼痛通路中的信息流。

All living creatures have to deal with pain - it's an unpleasant, but vital experience that safeguards animal welfare and ultimately, survival. Pain is a warning, a signal that you need to do something. Normally you have two choices: either move away and escape serious injury; or, if you're already hurt, you simply have to cope with the pain. Your brain recognises the difference between these two kinds of pain and works out the best bodily response. Escaping pain means that an animal has to rapidly get up and go. It has to run, jump, perhaps fly or swim to get away from the threat - this is an active response to escapable pain. To escape the pain animals have to move and movement requires increased muscular activity. When muscles go to work in an emergency they demand increases in blood pressure, heart rate and breathing to fuel them with extra oxygen and nutrients. In contrast, there is no escaping the pain of a stomach ache. When you move, the pain stays with you - all that can be done is to endure it, to try and cope with it. This is a passive response to inescapable pain. The best thing to do is to try and protect the injured tissues, which means 'lying low', keeping movement to a minimum - the opposite of an active response. To be effective, active and passive responses to pain are complex and they need body and brain to work together in a highly co-ordinated way. It is the body that responds to pain, but it is the brain that co-ordinates the respective changes in movement and in heart and lung functions. It is likely that escapable and inescapable pain is each controlled by its own separate connections within the brain. We have good evidence that this is the way that brain circuits control changes in blood pressure, but much less is known about the brain circuits that control changes in bodily movement in response to these different kinds of pain. The key aim of the present work is to find out whether different types of pain activate different circuits within the brain that control movement. In particular, we will focus on brain circuits leading to the cerebellum, the major controller of body movement in mammals. We will chart pain pathways within the brain that lead to the cerebellum and we will find out whether different pathways are activated by escapable pain (e.g. pain paths arising from the skin), as opposed to those activated by inescapable pain (e.g. pain paths arising from the guts). Also, by recording the electrical signals of individual brain cells, we will find out if painful and non painful signals are sent to the cerebellum by the same route. Pain also causes stress and anxiety, which affect the way in which an animal responds to, and copes with, pain. Stress activates parts of the brain that alter incoming pain signals, which in turn change the animal's response to pain. The final part of our study will see if the 'stress and anxiety' brain centres can alter the flow of information in pain pathways leading to the cerebellum.