At the beginning of my first ever neurology tutorial, the lecturer stood up and threw a question out to the class:
"What is pain?"
Several hands went tentatively into the air. Then were quickly withdrawn before the lecturer could point to them for an answer. The question is one of those that people think should be easy to answer, but on further reflection realise that it's not that easy. For most, the basic definition is that pain is the feeling or perception of irritating, sore, stinging, aching, throbbing, miserable or unbearable sensations arising from within the body. A neuroscientist would further classify pain as being the affective perception of nociceptive stimulation, and that it was not so much a sensation as a complex experience that is the product of interaction of various physical, mental and emotional components. Or, to put it a mite more simply, pain is both a physical reality and an abstract concept. Which isn't really an answer at all. So maybe there is no answer.
Function of Pain
What I do know is that pain is essential. Those who are born with an inability to feel pain, physical pain, tend to die young. This is because pain is instrumental in our navigation of the world. One woman born with this condition received intensive early training in order to recognise and avoid damaging situations. She died from sepsis aged 28, deformed and misshaped from degeneration of her joints. Why did this happen? Well, if you were to attempt to pull your finger back as far as it would go right now, you'd experience pain; this is your body's way of telling you not to do that because you're damaging yourself. Someone unable to feel pain could sit there doing this all day - till their finger snapped if they wanted. And they still wouldn't be able to feel pain. They'd burn themselves getting into a too hot bath. They'd get pressure sores while sleeping in bed because they're body is unable to sense that it needs to turn over. Pain is essential.
However, too much pain can be equally as damaging, as anyone with phantom limb pain or bone metastases can tell you. For these people, even high dose opoids bring little, if any, relief to their pain. Sometimes, people are so desperate to escape their physical pain they will consent to radical surgery to cut out nerves, nerve roots, and even parts of their brain. Tragically, this often makes little difference to their pain state. There is a large amount of money being ploughed into researching pain mechanisms; the reason for this is more than obvious.
Pain Perception
The term that describes the process by which the body is able to sense a painful stimulus is called nociception, (from the Latin 'nocere', to harm). The sensory cells that are activated by painful stimuli are called nociceptors, and there are several different classes of nociceptors, so, a chemical nociceptor will respond to substances such as histamine, a mechanical nociceptor will respond to pressure, and a thermal nociceptor will respond to an increase or decrease in temperature. There are two types of fibres that carry pain stimuli to spinal cord and brain. The fast ones are the Aδ fibres which are lightly myelinated. The C fibres are slower and unmyelinated. If you were to step on a sharp piece of glass, you'd have a sudden burst of localised pain that would cause you to quickly bring your foot off the floor to stop the pain caused by the glass cutting into your skin. This response is mediated by the Aδ fibres. After a few seconds, a dull pain will make itself apparent in the area where you have cut yourself. This is the response carried by the C fibres to remind you that you've cut your foot, and you should be a bit careful when using it while the wound is healing.
The body has yet to develop a piece of neural circuitry to force you to wear shoes at all times.
What happens to the stimuli transmitted by the nociceptive afferents upon reaching the spinal cord is a little more complicated. The information gets broken up and fed into both nerve tracts that lead to the brain and also sent into various spinal reflex arcs to facilitate non-conscious reactions - such as the sudden withdrawing of a finger away from a needle that you caught the sharp side of whilst sewing. The main tract that runs to the brain with nociceptive information is the spinothalamic tract, which runs to the thalamus of the brain, a small mass of grey matter at the base of the brain (from thalamos, the Latin for 'inner room', in turn derived from the Greek tholos, 'vault'). The thalamus is an amazing feat of biological engineering; the best analogy is to think of it as a telephone switchboard. A switchboard that is operated by the CEO of your brain. All sensory input (excluding only a part of the olfactory (smell) tract) and motor output passes through this amazing piece of tissue, and is subject to regulation by it. The thalamus breaks up the nociceptive stimuli and passes it on to the appropriate pieces of cortex for processing, such as the primary somatosensory cortex (S1), a small strip of brain that deals entirely with the sensory aspects of the body e.g., touch, proprioception, pain, etc.
Endogenous Mechanisms of Pain Control
Have you ever wondered how, as a child when you bruised your knee and ran to your mother for hugs and sympathy, her giving your knee a kiss and rubbing it better did actually make the pain go away? There is actually a neural basis for both of these magic remedies that mum would dole out.
Whenever we hurt ourselves, we always rub the area that we knocked as an instinctive reaction. And most of the time, it does actually stop the pain, or at least dull the ache. It's thought that by rubbing the area that we've just carelessly caught on a table as we walked past, we are activating the Aβ nerve fibres in our skin, which are mechanosensory fibres that carry information to our brains about touch. Theses fibres interact with interneurones in the spinal cord, which in turn synapse with the nociceptive fibres carrying the pain signals that have just been set off by that stupid bloody table, who put that there, etc., etc. These interneurones have a suppressive effect on the C fibre via presynaptic inhibition, acting as a gate to control the transmission of pain stimuli. This is technically just a hypothesis, called the gate-control hypothesis no less, but it does nicely explain the universal behaviour reaction to pain - the rubbing of the injured area. This is the mechanism taken advantage of by TENS (transcutaneous electrical neural stimulation) machines, where electrodes are placed on the skin over a peripheral nerve. TENS devices are often used quite successfully to treat some types of intractable pain.
Then there's mum's amazing skill at kissing away the pain. I suppose I don't need to tell you that it's got nothing to do with the kissing, so much as the belief the child has that his mum kissing his knee better will make his knee better. The kissing of the knee results in the release of endorphins, the body's own pain relief substances. Endorphins are small proteins that are chemically a part of the opoid family, and so have similar effects to morphine and heroin. They can also be as addictive as morphine or heroin, as proved by anyone who needs to get a gym fix in everyday. The endorphins are also implicated with regard to the placebo effect in pain relief. A placebo (from the Latin 'I shall please') is an inert substance that, none the less, produces a clinical effect. A good example in this case is in post-operative patients who, on being told that they are being given pain relief, are actually only injected with normal saline but still report a decrease in their pain symptoms. The belief that they are being given a treatment that will work is enough for the pain relief systems of the brain to be activated. This placebo effect is probably also a likely explanation for other methods of pain relief, such as acupuncture, hypnosis, and a loving mother's kiss.
Then there's the story of people who sustain horrific injuries and apparently feel no pain, or people that suddenly become super strong in order to lift a car off the person trapped underneath. This phenomenon is actually the result of descending inhibition coming from an area of the brain called the periaqueductal grey matter (PAG). It can be activated by strong emotion and stress, and also by those possessive of a stoic nature. It is this particular pain modulation mechanism that explains the difference in different people's pain thresholds.
Pain Dysfunction
There are two clinical pain states: physiological pain (i.e., pain caused by stimulation of nociceptors) and neuropathic pain (i.e., intractable pain that is maladaptive and has no logical stimulus).
Physiological pain is the everyday pain that we are all very familiar with, be it a paper cut or a broken leg. However, this pain state can often morph into slightly more sinister pain states due to the release of various substances (such as substance P and CGRP (calcitonin gene related protein)), resulting in a hyperalgesia, where even the slightest touch will set off an exaggerated pain response. These changes are not permanent however, and as the wound heals normal pain perception will be re-established.
Neuropathic pain is pain that results from damage to the nervous system that results in permanent changes to central nervous system (CNS) connections. There are various hypothesised mechanisms by which this can happen, but the result's always the same; an inescapable, constant pain that is resistant to many prescribed forms of analgesia. This type of pain is often associated with those who have either ripped out the nerve roots that supply a limb, or people who have an amputation injury. The pain appears to come from the deadened / missing extremity, and is very hard to treat. Often, patients will experience an allodynia - the interpretation of previously innocuous stimuli as being painful. For instance, if I were to stroke the cheek of a person who lost their arm in a motorcycle accident, they might experience an excruciating pain in their missing limb. The reasons for this are beyond the scope of this write up to explain unfortunately, but those with an interest in neurology and pain can read up further in various papers and in the more advanced neurological textbooks.
I did a whole three months of degree work focusing on pain. When you've studied a subject in depth, it's hard to know what should and shouldn't go into a brief summary. If you feel there's anything missing, let me know and I'll add it in if I think it's appropriate.