Thalamic processing of pain and putative control by cortical feedback


What is the manifestation of pathological pain in the mammalian 

brain? Our efforts ultimately aim to control neuronal activity in order to improve the outcome for patients suffering from pain.

Pain signals are relayed through the thalamus and are potentially altered (enhanced or attenuated) by cortical feedback (red). We investigate this possibility by controlling cortical feedback pathways optogenetically an using DREADDs in rodent pain models of acute and chronic pain.

Background: The sensation of pain is likely caused by specific activity patterns or signatures in neuronal networks that have primarily non-pain related functions, rather than a result of activity in specific, dedicated pain pathways. Common to pain and normal sensory signals is mandatory passage through the thalamus, a brain region which processes and relays information to the cortex.

The thalamus has rich, dynamic information processing abilities: signals are transformed in the thalamus by interactions between the thalamus and cortex, sculpting perception of sensory information. Importantly, in the context of the neural representation of pain, we need to better understand how normal and pathological thalamic activity contributes to pain perception. To understand the interplay between pain and thalamic signal processing, our group uses deep-brain electrophysiology, cell-type specific modulation of neuronal activity (optogenetics, DREADDS), and behavioral assays in awake, behaving mice

The mammalian brain (here from a mouse) is characterized by extensive corticothalamic feedback pathways. One pathway originates in the deepest layer of the cortex (layer 6) and provides a major input to the thalamus. In this transgenic mouse, the layer 6 corticothalamic pathway can be controlled specifically by optical stimulation of light sensitive ion channels expressed exclusively in L6 neurons and their axons (orange).

We focus on the following questions:

How does the thalamus encode pain?

A basic question is how thalamic spiking patterns determine how normal somatic stimuli are translated to either normal or a painful percepts. Knowing the “mapping” between thalamic spikes and pain allows us to investigate how changes in thalamic excitability lead to pathological conditions.

How does chronic pain develop?

When pain becomes chronic, a necessary if unpleasant sensation becomes a debilitating disorder. Dramatic and long-lasting changes in thalamic excitability are associated with the development of chronic pain. We investigate if such changes in thalamic excitability play a causal role in the development of chronic pain. Understanding pathophysiological changes in thalamic function and regulation associated with the development of chronic pain will help identify potential targets for pain treatment in order to prevent or reverse these changes on a mechanistic level.

Can we control thalamic pain transduction by activating “top-down” pathways?

The flow of information through the thalamus is controlled by top-down corticothalamic pathways which give the cortex the power to alter thalamic excitability. We investigate how chronic and acute pain perception is influenced by such corticothalamic “feedback,” with the specific goal of therapeutic intervention in cortico-subcortical communication in order to alleviate pain.



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