Not all pain is alike: How the spinal cord modulates our perception

Mr. Eippert, you start your new research group on pain perception this month at the MPI CBS. What do you find especially fascinating about this topic?

There are two sides of pain. On the one hand, it’s a signal essential for survival that alerts us of imminent or real injuries. People who are genetically unable to sense pain often die young as they live without this protective function. On the other hand, pain can heavily impair our quality of life, especially when it becomes chronic. I find it particularly interesting that at different times we can perceive the exact same physical pain stimulus as quite different.

What’s the reason for that?

It seems that individual differences in how pain is perceived are crucial. It has long been assumed that perception is passive. We receive stimuli from the outer world through our senses: there’s light falling on my retina and that is why I can see you; there are acoustic waves reaching my eardrum and that’s why I can hear you. However, in the last decade or two we have realized more and more that our perception is also heavily influenced by what we’ve learned. Based on these experiences we derive expectations about what will happen next. Thus, perception is also a very active process.

This can for instance also be seen in chronic pain patients: they know exactly what pain to expect when making a certain movement as they’ve learned it over a long time span. I would now like to investigate how predispositions such as these, or learned expectations, influence our perception of pain. It means, for example, that there can be differences between the pain signal that originates from a knee-joint for example and the pain information that is already stored in the central nervous system.

The placebo effect, which you’ve intensively investigated, is also based on expectations.

Exactly. We normally expect that we’ll feel less pain after taking a painkiller since we’ve learned this over the course of our lives. It gets interesting when it comes to taking a placebo, an inert ‘drug’ that should have no effect, but which we believe to be a real drug. In this case it’s the learned expectations alone that reduce the pain signals in the central nervous system. During my PhD in Hamburg we could show that such an expectation activates the body’s own pain inhibitors, especially endorphins. These substances influence the pain neurons in the spinal cord and indeed, we feel less pain.

What would you like to learn in this field at MPI CBS?

I’d like to look at the mechanisms by which our past experience modulates pain and explore how we can use this to intervene therapeutically. To do that I would like to determine whether a current model of visual and auditory perception, the so-called predictive coding model, also applies to the perception of pain. According to this model the brain constantly makes predictions about the next sensory stimulus, compares them with the current status and forwards any unexpected deviations, the so-called prediction errors, to a higher neuronal level. That means the brain might be primarily “interested“ in the deviations, as these signal valuable new information. So far, it has been assumed that these processes take mostly place in the higher parts of the brain, such as the cortex.
We think however, that in the context of pain the spinal cord, an evolutionarily old structure that has barely changed in vertebrates, might also play a crucial role in these fundamental processes of perception.

In what way? What role does the spinal cord play in pain perception?

This is exactly what we want to find out. We already know that it’s the first relay station for pain signals on their way to the brain. Pain from any part of the body first arrives in the spinal cord, it’s kind of the eye of a needle. Any change of the pain signal at this central station can therefore have vast consequences for what reaches the higher brain areas. As the first station of pain processing, the spinal cord is also the first location where pain can be inhibited. Therefore, we assume that the spinal cord plays an important role in situations where we experience the same pain differently, for example when we are distracted or under the influence of the placebo effect.

Perception and spinal cord—how do they actually relate to one another? Isn’t perception something that takes places as a higher cognitive ability in the cortex?

Those are good questions. The latter I would answer with “yes”. However, the process of perception likely begins in the lower levels of the central nervous system. A study has shown, for instance, that people who are able to inhibit pain processing in the spinal cord through cognitive strategies (such as distraction) also feel much less pain. Psychological factors, such as our expectations, indeed seem to be at work at a very deep level in our nervous system.

Furthermore, it’s important to note that pain is composed of many components: where it occurs, how strong it is and how unpleasant it is. These factors are processed in different parts of the brain. Possibly, the beginning of these various aspects can be already be found in the spinal cord. This is another topic which we would like to investigate – but it will certainly be a big challenge since the spinal cord is hard to investigate.

Why is that?

The spinal cord is only as thick as a thumb. With current MRI methods our spatial resolution is about one millimetre, which means we only have about 10 to 15 data points in a cross-section of the spinal cord. Furthermore, it is located very close to the lungs and is also influenced by the heartbeat: each time we breath or our heart beats, the image of the spinal cord is blurred, and this happens to a much greater extent than in the brain.

In addition to the perception of pain, what would you like to investigate at the MPI CBS in the upcoming years?

Due to the technical difficulties I just described, we would like to improve the methods for investigating the spinal cord. That means, for instance, developing better models for eliminating the disturbing influences from the heart and lungs, and also developing methods that will allow us to reach resolutions below one millimetre.

In parallel, we would like to reach a better understanding of how the scarcely researched spinal cord works. Which aspects of perception is it involved in: for instance, where is the intensity of our pain processed? How do the different parts of the spinal cord, for instance the cervical and lumbar sections, cooperate with each other?

During my time Oxford, we also discovered that the spinal cord—like the brain—never rests, even when we’re not doing anything. Up until now, these continuously fluctuating levels of activity have mostly been associated with higher cognitive abilities in the cortex. Our findings seem to suggest there is a continuous information exchange between the spinal cord and the brain, or that autonomic centres in the spinal cord generate spontaneous activity. As you can see, the spinal cord is highly unexplored terrain, to which we will dedicate our research.

We’re looking forward to your results. Mr. Eippert, thank you for this conversation.

The interview was conducted by Verena Müller.