Pain mechanisms: How does pain work?


How does pain actually work? I mean we all get pain and some people like myself get pain that even doctors struggle to understand. I have found that if you understand your pain or the way pain works then its easier to deal and cope with it. Therefore I’ve recently started by Pain masters course and we are learning about how pain is processed. I thought I would share with you all how exactly it works. In some parts it is very detailed but I have tried to keep it as straight forward as I can.

There are 3 main types of pain:

  1. Nociceptive/ inflammatory
  2. Neuropathic
  3. Somatic/ viscera

There is 3 different levels of pain processing:

  1. peripheral mechanism (detection + transmission
  2. Central mechanism (transmission processing
  3. Central mechanism ( modulation)

Inflammatory Pain: Peripheral/nociceptive pain

This is the most common pain you will experience and is when you have damaged a tissue structure often through inflammation. It is based on nociceptors picking up signals from their sensors, to then send a message to the brain telling them there is damage or inflammation in the area so it can do something about it.

The different stimuli/signals from sensors can be found in the:

  • Skin
  • Muscle
  • Bone
  • Tendon + ligaments
  • Viscera (organs)

What stimulus do the sensors measure:

  1. Temperature
  2. Mechanical (movement, friction, shearing ect.)
  3. Chemical (change in pH, hormones ect.)

Inflammation: is the body response to damage from the different stimulus mentioned above. The inflammatory response involves releasing chemicals (cell mediators) and white blood cells to help reduce the inflammation and damage.

The mechanism:

The stimulus (see above) damages area and is picked up by the sensors. The sensors will sound the alarm by releasing chemicals also called cell mediators (theses include cytokines and neurotransmitters, for more details look at the table below).

The chemical mediators will do two different things one is the local reaction and the other is the message that goes up to the brain.

Local reaction to inflammation:

The chemical mediators or chemicals will increases the amount of white blood cells in the area. It will also increases size of blood vessels surrounding the damage (vasodilation). It will also tell the plasma proteins in the blood to leave which takes some water with it and this causes the swelling, redness, heat.

inflammatory process


Message to the brain: (Wind up Mechanism)

These sensors will be activated send a message (action potential) to the dorsal horn in the spinal cord this message is transported through the primary/1st order neurons mainly the A delta or C fibres. The A delta fibres releases a chemical (glutamate) in order for the nerve to send the message. It will also increase the number of pathways (axon terminals) available to send the messages.

windup mechanism

Once in the dorsal horn the messages are then sent between the nerves (synapse) to the Central Nervous System. In the central nervous system the message is then processed, modified and increase the signals to let the brain know there is damage. It will also stimulate more neurotransmitters and receptors which will release more chemical increase the intensity of the pain.

Once the messages are in the higher centres of the brain will then process and control the pain though ascending and descending pathways.

If the C fibres are repeatedly stimulated it can decrease your pain threshold and increase the responsiveness to pain.

Ascending pathways:

Ascending pathways is from the spinal cord upwards to the thalamus + limbic system.

Once in the spinal cord the chemical (glutamate) that lets the nerves send the messages will bind to nerve cells that send messages between themselves (interneurons) + sensory neurons (2 order). This will happen in lateral spinothalamic tract of the spinal cord.

From the Spinothalamic tract the message will cross to other tracts and to the thalamus (between the cerebral cortex and mid brain) in the brain. Once in the thalamus the message will be transferred (synapse) to primary sensory cortex of the brain through 3 order neurons which will tell the brain the location and intensity of the pain.



Symptoms of ascending pathways of pain:

Dull aching pain: Is caused when the C fibres releasing glutamate and another chemical called substance P.

Extra Info:

Spinothalamaic tract = Is the pathways for sensory information from the skin all the way to the brain (thalamus). It is made up of two pathways called the neurospinothalamic + paleospinothalamaic

Neurospinothalamic:This tract or pathway goes to the somatosensory cortex which detects and causes the immediate response to damage.

Paelospinothalamic tract: This tract is responsible for the limbic or emotion response to pain. It activates the pathway to control and decrease pain. It also starts the more general (visceral) response to pain.

Descending Pathways:

Descending pathways are from the midbrain + the brain stem back down the spinal cord this is called a top down affect. They will be sent to either cortex + homunculus or the emotional control centre of the brain (Limbic brain including the hypothalamus periaquedual grey + Amygdala. They normally cause more vague or diffuse pain.

The cortex +homunculus: tell us the location + intensity of pain

Limbic brain + Amygdala: Tell us and control the effects that come with pain including fear, anxiety, sleep, mood.

The messages to the spinal cord can happen so fast that they can reach the brain faster than you will realise which is why you might not realise your hurt till after the accident.

Extra science bit:

This is just more information for those interested. In the inflammatory response I mentioned the body releases chemicals (cell mediators) to deal with the information these include:

Chemical:                                                                     Function:

Bradykinin cause blood vessels to enlarge and decrease blood pressure
Serotonin (5-HT) regulate and control the activity of neurotransmitters in the nervous system
Postaglandin contraction and dilation of blood vessels all around the body
Hydrogen ions (H+) changes hydrogen ions
Adenosine triphosphate – ATP Power house/ transports the chemical energy within cells for metabolism
Histamine works in the immune reaction on the capillaries (small blood vessels around the white blood cells it is also involved in neurotransmission
Substance P controls and transmits nerve and pain information throughout the spinal cord and brain
CGRP: (Calcitonin gene related peptide) works in the nervous system as to increase the size of blood vessels as well as transmit pain


Nerve Pain

Damage to the nerve cells in either the periphery or the central nervous system. The actual way the nerve is damage has no effect of the pain or the symptoms you get and normally affects the channels (TRPA, sodium, potassium and calcium channels) that process the pain.

Channels including the TRPA channels can be activated and not cause pain even if they are abnormal to start with. They can be slightly activated mildly for example through food like chilli, garlic, horseradish and cinnamon or they can act normal until triggered by something, ie. Cold weather.

Channels normally involved in controlling nerve pain are:

  • Calcium which acts as the clutch
  • Potassium which acts as the brakes
  • Sodium which acts as the accelerator

When you have pain the signals and chemicals normally sodium (Na) will accumulate round the damage causing abnormal activity. It will then alter the other channel functions normally the calcium (Ca) and Potassium (K) that setting off the neurological pain. It will also decrease your threshold to pain and make it easier for the sensors to be set off in the future.

control mechanism


Nerves activated without sensory stimuli will cause spontaneous pain and this doesn’t have to be from things that would normally cause pain. This will increases the sensitivity of the nerve which can cause shooting pain, pins and needles.

Somatic + visceral pain:

Somatic Pain: Localised pain due to an increase in the concentration of sensory information.

Visceral pain: Vague poorly localised pain that’s more unpleasant than sharp and can cause a nauseous feeling.

Chronic Pain:

If you have it for a long time the area where chemicals can attach to will increase which means your more likely to get pain for longer and it won’t take as much for it to come back again. Chronic pain can also change over time as there are often multiple mechanism going on at once. The changes are often to the high centres of the brain and it normally affects the release and production of neuro chemicals (neurotransmitters) including the adrenaline, no-adrenaline and serotonin. All theses chemicals will increase the sensitivity to the area.

The wind up mechanism I mention earlier if repetitively activated can maintains chronic pain. When I said it can increases the responsiveness to pain I really do mean it:

Chronic Pain: The brain will fire 36 messages in relation to pain (action potentials

Normal pain: The brain will fire 9 messages in relation to pain (action potentials)

No wonder it also increases the area of response receptor field and intensity to pain.

Some symptoms of chronic pain:

  • Allodynia: Pain in response to a non painful stimuli
  • Hyperalgesia: Increase sensitivity to pain + stimulus

Control (modulation) of pain

The control (modulation) of pain occurs in two different areas of the brain:

  • Periaqueducatal grey (midbrain)
  • Raphe magnus nucleus (medulla)

The nerve stimulated from painful stimulus to help control and prevents the pain signals. The nerve cells that send the signals back down from higher in the brain back down to the area of damage (descending neurons) release neuro chemicals (Neurotransmitters for there role see the table later on).

How the emotional centre of the brain help control pain:

The emotional centre of the brain will work primarily through the descending pathways mentions above in times of extreme stress. The messages in the emotional centre will take place in the dorsal horn of the brain in the hypothalamus periaquedual grey (raphus magnus nuclei) + They are also the site of the bodies natural opioid receptors.

The message to this area will activates the nerve pathway in the brain stem (the hypothalamus periaquedual grey mentioned above) where it is either turned off or on by the bodies natural opioids.

If the nerve pathway is turned on nerve will releases nerve chemicals like serotonin + noradrenaline (see table below) that will transfer the message through nerve cells (interneurons + 2nd order neurons) to stop the messages from telling the brain (spinothalamic tract (rex laminae 1,2 + 5) to cause pain and release the bodies natural painkillers (endogandenous cannaboids)



Neurotransmitter Function
Noradrenaline increases alertness, promotes vigilance, restlessness, anxiety enhances memory processing. It can also increase your heart rate, blow flow to muscles blood pressure and blood sugar. Reduces blood flow to the gastrointestinal system.


Adrenaline Increasing blood flow to muscles, blood round the body, blood sugar levels and pupil dilation.
Seratonin (5-HT) Reduced the size of your blood vessels. Controls memory, learning, mood including aggression, anxiety, thoughts, depression and sleep
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1 Comment

  1. Julie says: Reply

    My name is Julie and I am a runner with CRPS. I am a CSCS and PTA and I recently had to close my gym due to the fatigue. I’ve had CRPS since 2014 in my left foot from bunion surgery and it’s the bone form with the osteopenia. I was treated in Italy with neridronic acid which ended the stress fractures from the osteopenia. I am constantly trying to find ways to stop the glia cell activation. I think that exercise is the best way even though everyone else thinks that I am crazy. Here is a great, new PubMed study on exercise for neuropathic pain.

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