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Understanding Pain, A Ten+ Week Ecourse: Part 7

By Jonathan Blood Smyth

Week 7. Central sensitization

Welcome to the seventh instalment of my Ten+ Week Ecourse, I hope you find it interesting and stimulating.

Part Seven continues with the concept of central sensitization, an important idea if we are to make any headway understanding the different types of pain conditions.

This is part of the plastic nature of the nervous system and it contributes to a significant up-regulation of the pain system.

You are welcome to publish this course in your newsletters or on your web site, on condition you do not alter it and that you keep the resource box at the bottom of each instalment.

Last time we talked about the way the pain system is plastic and can learn and change its outputs in response to what comes in. We also went through what happens after an injury in terms of the response of the nervous system.

I know you want to move on to manage your pain, or manage people with pain, on to real pain management strategies. But try and be patient, we really do need to understand this stuff if we are to be effective.

Central Sensitization

The changes of central sensitization occur at the cellular level within the spinal cord and brain. They illustrate the ability of these neurons to change in response to pain inputs. This ability is called plasticity.

NMDA Receptors
Receptors are cells in the nervous system which respond to one or several chemicals, leading them to fire off. We happen to have receptors in our nervous systems which respond to chemicals from asian poppies. Heroin!

Receptors to the amino acid receptor NMDA type are implicated in the development of central sensitization. Release of excitatory chemicals from the central ends of pain nerves as they connect into the central nervous system causes a series of changes in the spinal cord nerves they synapse with.

These changes make the NMDA receptors and neurons more sensitive to further release of excitatory chemicals. The result is that the nerve cells become more excitable, more easily firing off and with greater output strength.

However, once the pain system is activated it doesn’t take much to produce pain and even innocuous input such as touch can do it. Up-regulation refers to this increased response of the pain producing system to decreased inputs.

Nitric oxide production
The increased excitability of the cells caused by the NMDA process increases the calcium ion concentrations, which stimulates the production of nitric oxide. This is thought to be able to diffuse out of the cell and may be a factor in the spread of excitement which seems to occur in spinal cord nerves.

Glutamate receptors other than NMDA
NMDA receptors may not be that important in the development of all types of central sensitization. They are thought to be more important in thermal sensitization and less in mechanical.

Other glutamate receptors exist and may drive the acute mechanical sensitization we see in injury and other pain syndromes.

Neuroanatomical reorganization

This is an important and interesting concept. It may be important in contributing to up-regulation, and help explain some changes which occur especially in nerve injury.

After nerve injury, incoming myelinated axons which normally make connections in lamina 3 and 4 of the spinal cord can sprout into lamina 2 and make connections there. In this way incoming nerves which conduct touch and pressure could connect directly with the pain conducting nerves in the spinal cord.

This may be an explanation for allodynia, where an input which is not normally painful is felt as pain. I think of it as a form of short-circuit or mis-wiring, leading to the wrong information being received by the brain. In this case the wrong information is pain.

Responses of the cell groups in the spinal cord

The wide dynamic range cells are common in the deeper laminae of the spinal cord. They take inputs from pain and non-pain nerves and respond in proportion to the intensity of the input. If they become sensitized they may fire off a much higher rates, even following mild touch or heat stimulation.

This may help explain secondary hyperalgesia, where pain is felt on stimulation of normal, non-injured tissues.

Nociceptive-specific cells
Cells which are specific to pain transmission are common in the more superficial spinal cord laminae. They get their inputs from unmyelinated C fibres, and do not usually respond to non-harmful inputs.

However, the reactions of these cells can change in response to sensitizing inputs from pain nerves. They start to react to inputs from myelinated nerves which would not normally cause a response.

The results are felt at higher levels in the nervous system and may be a factor contributing to increased perception of pain from inputs from both injured and un-injured tissues.

Summary of central sensitization

I know it’s a bit mind boggling, at least it is for me, but an understanding of this is vital to assessing and managing pain syndromes. If you or your patient has a highly sensitized nervous system this both explains some of the “odd” features and makes you think about how you might treat or manage the problem.

There are five major ways which tissue injury causes up-regulation of the pain producing system, leading to increased pain perception:

  1. The response thresholds of peripheral pain nerves reduce, so they are more likely to fire with peripheral stimulation.
  2. Previously inactive (”silent”) pain receptors are activated by the inflammation process, increasing the numbers of active pain receptors available.
  3. Peripheral input can cause changes in the myelinated (non pain transmitting) nerves, making them behave like pain transmitting nerves.
  4. Central sensitization can lower the levels at which the spinal, pain-processing cord neurons respond.
  5. Central sensitization can increase the effect of inputs which were previously non-painful, such as input from large, myelinated neurons. These can then be interpreted as pain and damage.

This ability of the nervous system to be so plastic, and to bring in extra pain nerves and nerves which don’t normally contribute to our pain experience, explains why an injury can cause such a strong up-regulation of the pain system.

Next we move on the next part of this story, how pain affects our motor responses, our movement.


Understanding Pain, A Ten+ Week Ecourse by Jonathan Blood Smyth. The Physiotherapy Site is your resource for orthopaedics, joint replacement, physiotherapy and pain.

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