Characteristics and consequences of subcellular calcium signalling in spinal neurons and glia in chronic inflammatory and neuropathic pain

Background:  

Psychophysical studies have documented that the two chemosensory systems of the nose, the olfactory system and the trigeminal system, do not operate independently of each other. Instead, non-nociceptive olfactory stimulation can increase the perception of pain while nociceptive trigeminal stimulation can decrease olfactory perception. Project A04 was designed to identify and characterize points of interaction between these two systems at the levels of sensory endings in the periphery as well as in second-order neurons in the trigeminal brainstem. Furthermore, the impact of non-nociceptive input on nociceptive trigeminal signaling will also be examined in the cornea and in the dura mater, using non-nociceptive cold fibers to generate innocuous sensory signals. The general goal of this project is to identify mechanisms that may underlie non-nociceptive modulation of painful conditions, such as headache.

A04 image

Working-Hypothesis:

  Co-stimulation of non-nociceptive afferents in nose, cornea and dura changes activity patterns of second-order neurons in the spinal trigeminal nucleus during application of a nociceptive stimulus. 

Project sections: 

1. Characterization of trigeminal afferents from nose, cornea and dura

2. Examination of afferent convergence on the spinal trigeminal nucleus

3. Cross-talk between peripheral nociceptive and non-nociceptive fibers

4. Effects of non-nociceptive co-stimulation on second-order neurons

5. Modulation of nocifensive behavior by olfactory stimuli

Methods:   

Project A04 uses a combination of neuroanatomy, electrophysiology and behavioral studies. To trace the system of afferent fibers targeting the spinal trigeminal nucleus, we use a range of genetically encoded labels in nociceptors, cold fibers and olfactory sensory neurons. Neuronal activity will be monitored mainly using extracellular single-unit recordings from isolated sensory organs and from the brain stem of anesthetized animals. The impact of olfaction on nocifensive behavior will be examined using a TRPV1-mediated, aversive two-bottle-choice test. 

Scientific goal: 

To establish whether and where trigeminal nociceptive processing can be modulated by olfaction and somatic non-nociceptive afferents. To this end we plan to identify structural and functional points of inter-modal cross-talk in primary afferents, second-order neurons, and to characterize cross-talk effects on behavioral patterns.

 

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