Pain and the immune-system

 beheerder    04 Apr 2018 : 09:30


In one of the latest CRAFTA Blogs my lovely colleague Gemma from beautiful Barcelona was writing about Bruxism and how to interpret, assess and treat this condition.

In one of the latest CRAFTA Blogs my lovely colleague Gemma from beautiful Barcelona was writing about Bruxism and how to interpret, assess and treat this condition. She perfectly described the important role of clinical reasoning processes when treating patients with several problems like pain and movement dysfunction or symptoms like dizziness or tinnitus. Gemma referred to Louis Gifford’s Mature Organism Model, which is not just a very clever system to understand pain mechanisms, but also to use it as therapeutic tool for patient education.
Gifford described a cycle of INPUT – SCUTINISING – OUTPUT that is able to facilitate itself, and is also under certain external influence, as it might be stress or other emotional situations. But there are not just certain external factors that are able to influence the peripheral and central processing of pain disorders. Since several years, scientists come up with lots of data to the role of the humans´ immune system on pain and other, quite complex, diseases.

The Immune-System and Pain?
The immune system consists of loads of organs and cells and is, next to the nervous system, the most complex organ system in the humans´ body. It is working as a very effective protector against a multitude of pathogens like viruses, bacteria and other microorganisms. Furthermore, it monitors the body to effectively destroy tumor-like cells, that permanently grow in our body but due to the several immune-cells don´t have a chance to grow. There are some immune reactions everybody knows quite well. Those reactions are very important mechanisms to heal tissue damage or to survive diseases:

  • Inflammation (distribution of histamine, leukotriene…)
  • Fever (raising the bodies core-temperature to “kill” unfamiliar intruders)
  • Building antibodies (e.g. influenza)

Our nervous system contains billions of neurons. That cells are connected to each other via, as well, billions of synapses. The structural and functional “neighbor” of these neurons are immune-cells, namely microglia, astrocytes or oligodendrocytes. You have to imagine those “neighbor”-cells as quite silent observers. In contrast to neurons, those cells do not have the task or even the ability to send information from the periphery to the central nervous system and back (conduction). They are just interacting and communicating with the nervous system. As long everything is okay, they remain quite silent. As written before, it is obvious that, as soon something is going on, think about intruder activation (viruses) or tissue-damage, those cells send their special tools to the specific location to start the healing processes via inflammation. They start to fight against bacterial infections via fever and macrophages, also called “eating-cells”.
We already know quite well the function of the nervous system (peripheral nerves, the spinal cord and the brain) in acute and persistent pain mechanisms. If peripheral and central sensitization, because of multitude ongoing processes, develop, symptoms can remain without tissue damage, just because of sensitizing processes in the dorsal horn of the spinal cord. These processes work because of neurotransmitter release (e.g. glutamate or aspartate) that facilitate neuronal conduction to suprathalamic, cortical areas. The brain decides if the incoming stimulus is dangerous or not. Under certain circumstances the brain can´t differentiate if it is dangerous or not and normal touch or easy movements get painful because of a maladaptive processing.
Now, what’s the immune systems role now?
Though it is sometimes not very comfortable and annoying we actually are happy about the reactions of our immune system and that it is working like that. But in the last fifteen years, scientists found out, that the immune-system, especially our microglia and astrocytes might also play an important role in the persistence of certain chronic pain disorders. It seems like those cells have an anti-inflammatory effect, as well as a pro-inflammatory effect. That doesn´t sound very logical but research in cell-physiology shows quite remarkable results.
If a certain nociceptive process is going on long enough, microglia and astrocytes start to pour out glutamate into the synaptic gap, that means that the already sensitized dorsal horn gets even more sensitized and more “danger”-information has to be scrutinized in your brain.
A scenario you wouldn´t wish.
So maybe the following metaphor is not the best one, but it describes in simple words what is going on when your immune-system is influencing the nervous-system in its role of nociception:
“The alarm system (brain) of your beloved house and garden (body) is malfunctioning (maladaptive mechanism, central sensitization) so that it starts to yell and ring all the time the cat (not dangerous) is entering via the backdoor. Even more now, you have some neighbors (immune-cells), that most of the time watch for your house but now, however, start to throw stones at your house and yell: “Hey, hey!!! Watch out, this cat it is dangerous, I remember this from the last time it entered your garden!!!”

4 4 Blog 01

Simplified view into the dorsal horn: The immune cells start to facilitate sensitizing processes by pouring out neurotransmitters into the synaptic gap!

Till now those mechanisms of the neuro-immunological system are not completely understood. Especially the role of the immune-cells, as pro- and / or anti-inflammatory factors remain unclear. What we know is, that the immune-system is under the control of our vegetative nervous system. This knowledge leads to the importance of the psycho-immunological context of stress-disorders and pain.
Chronic headache is the second common persistent neuro-musculo-skeletal disorder right after persistent low back pain. Like in all (chronic) disorders it is important to watch at this condition with a biopsychosocial perspective and try to understand the patient within a holistic approach. It is important to listen to your patients’ story carefully and also ask specific questions regarding health issues and yellow flags. With the knowledge of neuro-immunology several chronic face and head syndromes can be viewed and managed in a different light. Remember, that important factors that can be influenced BY the immune-system, but also have impact ON the immune-system are:

  • Sleep
  • Nutrition
  • Stress disorders
  • Malign diseases in the patients´ history
  • Infections

You don´t have to be a psychologist or a specialist in dietetics and nutrition but you have to recognize the facts, because now you know that this can be signs of a maladaptive working neuro-immune-system. So, in the next step go on, build a network of specialists in this area and communicate with them. If you treat or manage patients with chronic, especially neuropathic, pain disorders you have more re-assessement parameters than pain-threshold and movement dysfunctions. The mature organism model, used in CRAFTA, gives you a nice guideline to think into this direction.
Clinical implications.
What does this knowledge mean for the treatment of head and facial pain? Do we need some kind of paradigm shift leading to a more multimodal management of chronic head and facial pain states and does it also indicate to a broader understanding in acute situations?
The therapists clinical reasoning process should include an understanding of influencing factors for the patients’ situation. That means that the questioning in the beginning also regards to eating habits, sleeping disorders and could be expanded with psychosocial screening tools. This requires a lot of experience in communication and empathic social skills. The challenge is to guide the patient through his situation and also get into a good self-reflective approach.
If therapists assess and acknowledge those challenges regarding to neuro-immunology factors it is necessary to cooperate with other professions but also be clear and linear in the clinical process. Nevertheless, it might be useful to treat the patient also with endurance training, strengthening exercises or neurodynamic movements for the whole neuraxis (SLUMP movements etc.). All those applied, sometimes non-specific, techniques have several effect-mechanisms. Always be aware that every intervention has multifactorial effects, may they be mechanical, neuro-immuno-physiological or psychological. Treat the human – not the diagnosis.

4 4 Blog 02


Allianz chronischer Schmerz. (2018). Allianz chronischer Schmerz Österreich. Retrieved February 21, 2018, from
Gifford, L. (2014). Aches and Pains. CNS Press Ltd., Kestresl, Swanpool, Falmouth, Cornwall, TR11 5BD, UK.
Haydon, P. G. (2001). GLIA: listening and talking to the synapse. Nature Reviews. Neuroscience, 2(3), 185–193.
Milligan, E. D., & Watkins, L. R. (2009). Pathological and protective roles of glia in chronic pain. Nature Reviews. Neuroscience, 10(1), 23–36.
Tracey, K. J. (2009). Reflex control of immunity. Nature Reviews. Immunology, 9(6), 418–428.

News Categories