Peripheral vs Central Sensitization

To understand peripheral vs central sensitization, you need to understand how the nerves in your body are organized, and the different ways in which they can carry pain messages.

There are basically two big divisions of nerves. One type of nerves are myelinated, and the other type are unmyelinated. Myelin is the nerve sheath that covers some nerves and will speed up the transmission of all the messages along these nerves.

Peripheral Sensitization

The number of unmyelinated nerves outnumbers myelinated by many times. The most common unmyelinated fibers are C fibers, and these only carry pain messages. They carry them slowly and are found all over your body, ready to turn on when there is a pain message.

When C fibers are turned on, they do two things. The first thing they do is carry pain messages up to the brain.

The second thing they do is at the nerve endings, which is where the nerves begin in your body. The C fibers at the nerve endings are capable of turning on and producing the substances of the inflammatory soup.

The Inflammatory Soup

The inflammatory soup is the name for a group of substances produced in your body when there is inflammation. There’s substance P, antihistamine, prostaglandin, bradykinin, and many others.

These are the substances that your blood provides when there is damage to your body. When you’re injured, the blood vessels in the area become leaky and these substances emerge to heal the damage.

If you twist an ankle, ankle, initially, you feel the pain because of the tissue damage. After that, you feel the pain because the whole of the area has become inflamed in order for your body to heal it. These substances in the inflammatory soup are all algogenic, meaning they cause pain. They are also a part of the healing process.

The C fiber nerve endings can also produce this inflammatory soup and this is the main cause of peripheral sensitization.

If you think logically, why should the C fiber nerve endings be able to produce the inflammatory soup? The answer is that if the fiber is turned on, it will be telling you that there is damage in the area. So it would be very efficient if the fiber itself could also start the process of healing.

From a teleological point of view, this makes sense. However, what you’re hoping is that the fiber will only turn on when there is damage and will then turn off the inflammatory soup production when things start getting better.

Neurogenic Inflammation

Most of the time, this is exactly what happens. But sometimes this doesn’t happen and this is when peripheral sensitization can occur. This can be a very powerful cause of pain. Its other name is neurogenic inflammation: inflammation arising from the nerve endings. It’s a significant factor both in healing and in chronic inflammation.

Peripheral sensitization due to neurogenic inflammation can be a factor in chronic tendinitis. In fact, this type of inflammation is an important factor in anything that has ‘itis’ at the end of it.

This includes: arthritis, tendonitis, tenosynovitis, myositis (muscle inflammation,) osteitis (bone inflammation,) and vasculitis (inflammation of blood vessels.)

So this is peripheral sensitization, and next we’ll look at central sensitization.

Central Sensitization

Central sensitization arises from the nerves in the dorsal horn of your spinal cord and the nerves in your brain.

These are the second-order neurons. The first-order neurons are located in your body, and the second-order neurons start at the dorsal horn of your spinal cord and go up to your brain.

When you have central sensitization, nerve messages are transferred onto your spinal cord at the dorsal horn. It is at this synapse (where two nerves connect) that messages can be amplified.

With central sensitization, nerve messages coming from your body can be normal – and should cause no pain. But if at the dorsal horn of the spinal cord, they are amplified, and by the time they reach your pain, what should have been a normal message, has been turned right up to be a message of pain.

The key issue here is that your brain is the organ which interprets messages from your nerves. If the initial message was normal, your brain doesn’t know that.

It only interacts and interprets the final message which reaches it. And if this message has been amplified en route, what you feel is a lot of pain, even when you have littler or no physical damage.

Diagram showing a pain message starting at your thumb, reaching your spine and being amplified, so you feel much more pain than you should

The second place messages can be amplified by central sensitization is in your brain. Researchers have shown that people with chronic pain have measurable changes taking place in their brain. Their brains actually adapt to being constantly bombarded with pain messages.

However, this adaptation is not a useful one, and what happens is their brain actually becomes better at processing pain messages. Larger areas of the brain are used to process pain messages in people with chronic pain, and this has been shown by functional MRI brain scans.

This is the second part of central sensitization: a neuroplastic change in the brain caused by being in pain for a long time.

Visual representation of a functional MRI brain scan. The brain on the left belongs to someone in chronic pain: larger areas of the brain are active when they feel pain.

Peripheral vs Central Sensitization: How do you Tell the Difference?

Technically, it can be difficult to tell whether you have peripheral or central sensitization. For some people, the pain is completely peripheral. Others have only central sensitization. More commonly though, people have a mix of both kinds, making it hard to separate out causes.

Practically, though, the treatment for both conditions is similar, so the exact causes become more academic than useful in terms of getting out of pain.

You can’t tell the difference between peripheral and central sensitization by the kind of pain you feel. This is you can only decode the final signal that reaches your brain.

The only way to tell them apart is by blocking the peripheral nociceptors (pain-producing structures.) So if the disc or joint or other peripheral structure is blocked by using local anaesthetic and the pain disappears, then it is due to a peripheral cause.

If you block the messages from the peripheral source with anesthetic and still have pain, then your pain is 100% central sensitization. The most classic example of central sensitization is phantom limb pain, where the limb and its nerve endings are completely missing, but you still feel pain.

However, most people have a mixture of peripheral and central sensitization, so if you block the peripheral source (ie. by putting local into a painful joint) and the pain is reduced, but not gone entirely, then you know it’s a mixture of the two causes.

In chronic pain, it is really common to have both peripheral and central sensitization occurring at the same time. 

Similarly, it’s very difficult to know if neurogenic inflammation is due to tissue damage, or peripheral sensitization, or a mixture of the two. This is because the inflammatory soup can be produced by many different structures.

It can be produced by the joint capsule if the joint is damaged. Tendons and ligaments can also produce inflammation. Nerve endings can produce these same substances and this is what turns on peripheral sensitization.

Therefore, it becomes very difficult to define accurately exactly what is causing the sensitization, and you have to look at other factors.

Factors like how long you’ve been in pain (should you have gotten better by now?) and how the pain behaves, (is it behaving like a structural or pain system pain?) are important to make an educated assessment of the underlying cause.

Realistically, if you have either form of sensitization, the things you’ll need to do to quieten it down are similar. Here’s where to find out more about whether your pain system is sensitized, and what you can do about it.