Physiology of pain

In its simplest form, the pain circuit in the body can be described as follows: pain stimulates pain receptors, and this stimulus is transferred via specialised nerves to the spinal cord and from there to the brain.

The pain stimulus is processed in the brain, which then sends an impulse down the spinal cord and via appropriate nerves which command the body to react, for instance by withdrawing 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, such as the gut and muscles, have fewer pain receptors. It is interesting to note that the brain itself does not have any pain receptors at all, and is therefore insensitive to pain.

Pain receptors are free nerve endings. There are three types of pain receptor stimuli: mechanical, thermal and chemical. A mechanical stimulus would be, for example, high pressure or stretching, and a thermal pain stimulus would be extreme heat or cold.

Chemical pain receptors can be stimulated by chemicals from the outside world (e.g. acids), but also by certain products present in the body and released as a result of trauma, 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).

Compounds called prostaglandins are released with painful stimuli, and although they don’t directly stimulate pain receptors, they do increase their sensitivity. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) decrease the effect of prostaglandins, that is why they work as painkillers. Paracetamol operates in the central nervous system and the NSAIDs are peripheral-acting substances.

Pain nerve fibres – 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 via two different types of nerve fibre: “fast pain” and “slow pain” fibres.

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 a sharp pain. After a few seconds, this becomes a sensation of “slow pain”, which is a duller and more of a burning pain. This slow pain normally lasts for a few days or weeks, but if inappropriately processed by the body, it can last for 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 fibres, although this term is relative because they are still microscopically thin, with a diameter of two- to five-thousandth of a millimetre. These nerves are called A-delta fibres. Because of their relative thickness, they allow the pain stimulus to be transferred very fast (at a speed of 5 to 30 metres per second), hence the name. This allows the body to withdraw immediately from the painful and harmful stimulus in order to avoid further damage.

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

The pain does not radiate, i.e. you feel it on a very particular spot. It is difficult to overcome this type of pain, even with strong painkillers. This means that if surgery needs to be performed, the pain of the incision cannot be taken away with strong opioids alone.

However, infiltration of the affected area or the nerve with a local anaesthetic will take away all sensation, including any sharp pain. This is what happens in surgery performed under local anaesthetic.

Slow pain, which starts immediately after the fast pain, is transmitted by very thin nerve fibres called C-nerve fibres (their diameter is between 0.2 and one thousandth of a millimetre). Because of their size, the pain impulse can only be transmitted slowly to the brain, at a speed of less than 2 metres 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 originating in internal organs such as the gut and the uterus – but not the brain, which is insensitive to pain. Whereas localised pain on the skin, like a small cut, is painful, localised trauma to an internal organ is not painful. For instance, when a surgeon makes a cut in your 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, massive injury to an internal organ can be severely painful, for example if a whole segment of bowel dies off (infarcts). Other examples include when a cystic duct is obstructed because of gallstones, when the urine bladder becomes overdistended because of a stone or enlarged prostate, and the well-known pain of labour.

This pain is poorly localised and is felt more diffusely, unlike pain on the skin, which can be exactly pinpointed. It also often radiates (e.g. gallbladder 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 effectively remove this type of pain if the appropriate nerves can be blocked.

Characteristics of fast pain and slow pain

Slow pain

Fast pain

Transmitted by very thin nerve fibres

Transmitted by relatively thicker (and therefore faster conducting) nerve fibres

Poorly localised

Well localised

All internal organs (except the brain)

Mainly skin, mouth, anus

Body wants to be immobile to allow healing (guarding, spasm, rigidity)

Immediate withdrawal of stimulation to avoid further damage

Pain often radiates, or is referred

Pain does not radiate

Effective relief from opioids

Little relief from opioids

Examples: labour pain, pain starting after fast pain from an injury

Examples: pain from a surgical incision

Pain transmission in the spinal cord and the brain
The peripheral nerves (nerves outside the central nervous system) 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, sleeping difficulties (because the pain stimulates the “wake centre”), and a depressed mood.

What can the body do to temper the pain sensation?
A very common remedy 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 fibres, and their input in the spinal cord receives preference over the input from the nerve fibres transmitting the pain.

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 has been sent up to the brain. In a nutshell, 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 there also exists a system of natural opioids. When a pain impulse reaches the brain, these opioids are released from their storage areas and bind with receptors in the pain pathway to block the transmission and perception of pain. Examples of these natural opioids are enkephalin, endorphin and dynorphin. How precisely this all works is not completely understood, but when opioids (e.g. morphine) are administered by medical staff to a patient with pain, these administered opioids bind with the same receptors in the brain to block pain perception.

Reviewed by Prof CL Odendal, senior specialist at the department of anaesthesiology at the University of the Free State, April 2010.

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