PAIN MODULATION

Neurobiological mechanisms of endogenous pain modulation

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 Obiettivo del progetto (Objective)

'Chronic pain is one of the largest medical health problems in Europe, affecting about 20% of all adults. To combat chronic pain, we need an improved understanding of the mechanisms underpinning pain. We know that pain is not an invariant mapping from the physical intensity of sensory stimulation to perception, but is subject to various modulating factors that reduce or enhance pain perception. Endogenous pain modulation involves systems that originate in cortical areas, which communicate – via subcortical and brainstem structures – with the spinal cord, where nociceptive processing is controlled. Previous research has focused on anti-nociceptive mechanisms, but it is becoming increasingly clear that pro-nociceptive mechanisms also play an important role in chronic pain.

This proposal will therefore be investigating the neurobiological mechanisms that underlie both directions of pain modulation, by using the models of placebo analgesia and nocebo hyperalgesia in functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) studies. A first objective is to investigate bidirectional brainstem control of spinal cord responses with dedicated fMRI tools. The second objective – which involves ultra high-field fMRI – is to characterize the subcortical-brainstem networks in detail that intervene between cortical and spinal processing. Finally, a third objective is to determine cortical pain control mechanisms by using MEG in combination with analysis of evoked and induced responses. All three objectives will put a strong emphasis on connectivity analyses.

The proposal will provide important insights into pro- and anti-nociceptive pain-modulatory processes at an unprecedented level of detail. Such an endeavor is clinically important, as malfunction of pain control systems is a key underlying factor in the generation and maintenance of chronic pain, which is an enormous burden not only for the affected individual, but also for health-care systems worldwide.'

Descrizione progetto (Article)

Researchers hypothesise that chronic pain is the result of an individual's inability to modulate, or control, pain appropriately. The dysfunction most likely occurs in the spinal cord, the first part of the central nervous system where pain signals are processed and relayed to the brain.

An EU-funded project, 'Neurobiological mechanisms of endogenous pain modulation' (PAIN MODULATION), aim to better understand how pain is experienced. The first phase of the project involved using functional magnetic resonance imaging (fMRI) to pinpoint the location of responses to painful stimuli. Investigators found that pain responses are located in the back of the spinal cord.

Next, investigators studied whether the spinal cord would respond to visual stimuli that are related to pain responses. They found that if a participant learned to relate pain to visual stimuli, the spinal cord responded. Interestingly, the more a participant expected pain, the weaker the response to the painful stimulus. On the flip side, the spinal cord responded to visual signals that predicted upcoming pain.

The pain response was also found to be dynamic. For example, if visual stimuli were no longer followed by pain, the spinal cord response decayed. These findings suggest that there is a top-down pathway from the brain to the spinal cord that modulates spinal cord neurons with the expectation of upcoming pain.

In the second phase of the project, researchers are conducting experiments using magnetoencephalography. This work will allow researchers to measure response time to pain in milliseconds, which is much faster than fMRI. Focusing on response time may add to understanding of the subjective aspects of pain.

The PAIN MODULATION project is mapping pain modulation capabilities of a healthy central nervous system. The hope is that these findings will provide guidance for studies in patients with dysfunctional systems who are suffering from chronic pain.