The pain stimulus is processed in the brain, which then sends an impulse down the spinal cord, via appropriate nerves which command the body to react, like withdraw the hand from a very hot object.

Perception of the pain stimulus: from the pain receptors to the brain

Pain receptors
Pain receptors are present everywhere in the body, especially the skin, surfaces of the joints, periosteum (the specialised lining around the bone), walls of the arteries, and certain structures in the skull. Other organs have less pain receptors (gut, muscle, etc). It is interesting to note that the brain itself does not have any pain receptors at all, and is therefore insensitive to pain inflicted to it!

There are three types of pain receptors: mechanical, thermal and chemical. A mechanical stimulus would be for example high pressure or stretch, and a thermal pain stimulus extreme heat or cold.

Chemical pain receptors can be stimulated by chemicals in the outside world (e.g. acids), but also by certain products that are present in the body and locally released upon trauma or inflammation or other painful stimuli. Examples of these substances are bradykinins, serotonin, potassium ions and acids (such as lactic acid, which causes muscle pain after heavy exercise).

Prostaglandins are also mediators that are locally released with painful stimuli, and although they do not directly stimulate pain receptors, they do increase their sensitivity. Paracetamol and NSAIDs have an anti-prostaglandin effect, and that is how they work as pain killers.

Pain nerve fibers – fast pain and slow pain
From the pain receptors, the pain stimulus is transmitted through peripheral nerves to the spinal cord and from there to the brain. This happens through two different types of nerves fibers: “fast pain” and “slow pain” nerve fibers.

What is “fast pain” and “slow pain”?
A pain stimulus, e.g. if you cut yourself, consists of two sensations. The first one is the so-called “fast pain” sensation, and is experienced as sharp. After a few seconds, this goes over into the sensation of “slow pain”, which is more a dull and burning. This slow pain normally lasts a few days or weeks, but if inappropriately processed by the body, it can last several months, and give rise to chronic pain.

Fast pain, like pricking yourself with a needle or touching a burning object, is mainly related to painful stimuli of the skin, mouth and anus.

It is transmitted by relatively thick nerve fibers, although this is relative, because they are still microscopically thin, with a diameter of 2 to 5 thousandth of a millimeter. These nerves are called A-delta fibers. Because of their relatively thick size, these nerve fibers allow the pain stimulus to be transferred very fast (at a speed of five to 30 meter/second), hence the name. This is all to make the body withdraw immediately from the painful and harmful stimulus, in order to avoid further damage.

It is well localised, meaning that a person can normally describe very accurately where exactly the pain is. The pain is sharp and “cutting” in nature.

The pain does not radiate, i.e. you feel it on the spot where it is actually hurting. It is difficult to overcome this type of pain, even with strong pain killers. This means that if surgery needs to be performed, the pain of the incision can not be taken away with strong opioids alone, unless so much opioids are given that they make you unconscious.

However, infiltration of the affected area or the nerve with a local anaesthetic, will take away any sensation, including any sharp pain (e.g. surgery performed under local anaesthetic).

Slow pain, which starts immediately after the fast pain, is transmitted by very thin nerve fibers, called C-nerve fibers (their diameter is between 0.2 to 1 thousandth of a millimeter). Because of their small size, the pain impulse can only be transmitted slowly to the brain, at a speed of less than 2 meters per second. The response of the body is to hold the affected body part immobile (guarding, spasm or rigidity), so that healing can take place.

Slow pain can also be the primary type of pain when it originates in internal organs: gut, uterus, etc., except the brain, which is an organ insensitive for pain. Whereas very localised pain on the skin, like a small cut, is painful, localised trauma to an internal organ is not painful, e.g. when a surgeon cuts a bowel, this is not painful at all (but for the surgeon to get to the bowel, he has to cut through skin, and that is why you need anaesthetic).

However, if massive injury occurs to an internal organ, it can be severely painful, for example if a whole segment of bowel dies off (infarct). Other examples are: when a gall bladder duct gets obstructed because of gall stones, the urine bladder gets overdistended because of a stone or enlarged prostate, and the well known pain of labour.

This pain is poorly localized, felt more diffusely, unlike pain on the skin, which can be exactly pinpointed. It also often radiates (e.g. gall bladder pain can be felt from the front to the back) or is referred to other parts of the body (e.g. pain from a heart attack can be felt in the neck or the arm).

Opioids are very effective in treating this type of pain. Local anaesthetics block all nerve transmission, so they also easily take this type of pain away, if the appropriate nerves can be blocked.

Pain transmission in the spinal cord and the brain
The peripheral nerves carry the pain impulse to the spinal cord. In the spinal cord, fast pain and slow pain are carried up to the brain via different pathways. The impulse of the fast pain goes to specific and limited areas on the surface of the brain (the cortex), allowing for the relatively precise localisation of the pain stimulus.

The impulse from slow pain is distributed diffusely in the brain. Each area of the brain elicits a different response, which explains the whole range of symptoms that pain can cause: such as suffering, difficulty in sleeping because the pain stimulates the “wake center” and a depressed mood.

What can the body do to temper the pain sensation?
A very common thing is “rubbing the pain better”. When you get hurt, you instinctively rub the painful area, which partly relieves the pain. The reason is that rubbing or pressing stimulates certain other nerve fibers, whose input in the spinal cord get preference over the input from the pain nerve fibers.

When a pain stimulus reaches the brain, the brain itself sends a signal back to the spinal cord via a very complex system of nerve connections, to diminish the transmission of the pain impulse that is sent up to the brain. Thus the brain puts a brake on the pain impulse as it enters the spinal cord. Important molecules in this process are enkephalin and serotonin.

In the pain processing parts of the brain also exist a system of natural opioids. These opioids are released from their storage areas in the brain when a pain impulse reaches the brain, and bind to receptors in the pain pathway to block transmission and perception of pain. Examples of these natural opioids are enkephalin, endorphin and dynorphin. How precisely this all works is not totally understood, but when opioids (e.g. morphine) are administered by medical staff to a patient with pain, these administered opioids bind on the same receptors in the brain to block pain perception.

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