Receptors and channels in pain

Published on April 2, 2014   45 min
0:00
So I'm Professor Tony Dickenson from University College London. And this presentation is based on receptors and channels in pain, how the integrated function of the nervous system, subjects to painful messages, deals with these external events.
0:20
Pain is an intriguing example of understanding and trying to gauge how external events, in this case from the body, impact upon function of the central nervous system. So peripheral events, peripheral sensory fibers, project into the spinal cord. The spinal cord then sends messages up to the higher centers. And in the case of pain, of course, it's an individual, personal experience that is built up. But what goes up, also comes down. And so the higher centers of the brain are able to alter mechanisms within the brain stem and change what we call descending controls, which, in turn, return to the spinal cord. And so the higher centers have the ability to modulate events at the first synapse within the spinal cord.
1:17
So if we look in a little bit more detail at these pathways, at the bottom left, incoming peripheral nerves, which are highly specialized, many of them respond to nonpainful stimuli, such as touch and temperature. But then we have a large number of pain-sensing fibers. And here there are a remarkable number of receptors and channels that respond to heat, to mechanical, and to chemical stimuli, all of which are painful. These are altered by damage to nerves themselves, or, indeed, damage to tissues, and they will input into the spinal cord. The spinal cord neurons integrate these messages, often, and unfortunately in the context of pain, amplify these messages and send them on to the higher centers of the brain. So at the top right, we have the cortex, the homunculus. These columns of neurons responding to particular parts of the body, and neurons within these columns are able to code the intensity of the stimulus. So our ability to locate pain and describe it are cortical mechanisms. But at the top left, there is the limbic brain and an equally important input from the spinal cord into these areas. The limbic brain's function is to control mood, to generate the sleep/wake cycle, to respond to external events. And so it's not surprising that ongoing painful inputs into these parts of the brain disrupt this function and lead not just to pain, but to fear, anxiety, and sleep problems that are common in patients. And then, from these limbic parts of the brain, we have the descending controls that return to the spinal cord. And so cognitive, proprioceptive, and mood changes occurring in the higher centers have the ability to modulate transmission at the spinal cord, and they can enhance it, or, in fact, they can inhibit it.
3:26
So these processes at every step of the pathway clearly involve neuronal signalling. And in the context of this lecture, we're going to examine the receptors and the ion channels that are involved in signaling pain, but also within systems in the central nervous system that are able to modulate pain. And as we go along, I'll point out how these targets relate to drug therapies for pain.
3:56
One very important point, though, is that all pains are not the same. So the differences in the three major types of pain that we understand are really due to differences out where the pain starts, out in the periphery. So in blue, there is this term, "nociceptive pain," that is generally used to describe pain caused by tissue damage, inflammation, sometimes noninflammatory, but generally tissue damage, chemicals released in and around the area of trauma. On the right, we have a very different type of pain, "neuropathic pain," where here there is a lesion or a disease in the sensory nervous system. And so the damage is within the nerve. The tissue is normal. And the events that initiate the pain are very different indeed. They're going to be ion channels, the key components of nerves. So the tissue and nerve damage have very different starting mechanisms. But in patients, pain is not that simple either. So low back pain and cancer pain are looked upon as examples of what is sometimes called mixed pains, were we can have elements of tissue damage and elements of nerve damage. And finally, the other definitions of pain involve its intensity and its duration.
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Receptors and channels in pain

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