Different functional roles of nociceptor subclasses in human

 

Project description

Chronic pain, especially neuropathic pain, and chronic itch are still major health burdens since the underlying mechanisms in humans are insufficiently understood. Activation of peripheral nociceptors and pruriceptors (unmyelinated peripheral nerve fibers, C-fibers).may lead to the subjective perception of pain and/or itch.  We assume that in human two different nociceptor classes have completely different functional roles in the perception of itch and pain. Mechano-sensitive nociceptors seem to be important for the discriminative component of acute pain whereas the mechano-insensitive nociceptors of humans play a crucial role in inflammation pain, neuropathic pain and in intense emotionally aversive acute pain. We hypothesize, that the central connectivity and signal processing of the input via these two systems is different and that therefore different emotional involvement and behaviour could result.

We will scrutinize the properties of different peripheral nociceptor classes with help of microneurography and psychophysics especially in plastic situations like neuropathy and examine the functional role of these two different systems with fMRI and psychophysics.

Microneurography allows to perform electrophysiological examinations in healthy subjects and chronic pain or itch patients on the level of single action potentials in single axons of nociceptors.

Vision

After establishing the neurophysiological basis of differential properties of the two human nociceptor classes, we will show that the activation of these two nociceptor classes result in different central signal processing and contribute to different aspects of chronic pain and itch. Knowledge about a pathway, crucially involved in the negative emotional aspects of chronic itch and pain perception, may lead towards specific targets for pharmacological modulation of chronic itch and pain.