A tale of two itches. Common features and notable differences in brain activation evoked by cowhage and histamine induced itch

Abstract

Previous PET and fMRI brain imaging studies targeting neural networks processing itch sensation have previously used histamine as the sole itch inducer. In contrast with histamine, cowhage-induced itch is mediated via proteinase activated receptors PAR2 and is transmitted through a separate spinothalamic pathway, therefore imaging the brain activation evoked by cowhage could provide further insight central processing of itch. We report for the first time a functional MRI Arterial Spin Labeling (ASL) study of neuronal processing of itch induced by cowhage analyzed in contrast with histamine-induced itch. We also explored the brain responses induced by histamine and cowhage combined in a tight sequence. The results of our analyses obtained in a group of 15 healthy volunteers suggested that cowhage and histamine co-activated a core group of brain structures, while also revealed notable differences. Core areas activated by both stimuli were found in the thalamus, primary and secondary somatosensory cortices, posterior parietal cortex, superior and middle temporal cortices, PCC, ACC, precuneus and cuneus. Cowhage induced a notably distinct and more extensive involvement of the insular cortex, claustrum, basal ganglia, putamen, thalamic nuclei and pulvinar. The differences observed between these two itch modalities were investigated to determine the impact of quantitative versus qualitative factors, and correlations between itch intensity and the patterns in brain activation were explored. Our analysis revealed that the most significant differences between cowhage and histamine itch were not affected by stimulus intensity, although a subset of regions displayed activations which were intensity-dependent. The combined application of cowhage and histamine highlighted the role of insula and claustrum in the processing of both itch modalities in the same time. The present results suggest the existence of overlapping but also distinct neuronal networks processing these two different types of itch.

TRP Channels and Pruritus

“…In a PET study, a positive correlation was found between the subjective intensity of histamine evoked itch sensation and the activity of the insula and the anterior cingulate cortex [43]. Moreover, Papoiu and colleagues [44] identified different cerebral activity patterns in itch evoked by histamine or cowhage.…”

“…Among them, PAR2, expressed by sensory neurons, is considered as a key molecule in itch sensation [66][67][68]. In experimental models, by using cowhage spicules (which contain the protease mucunain) to activate PAR2, a histamine-independent parallel itch pathway was identified and found to significantly contribute to chronic itch sensation [10,27,44,69,70]. Interestingly, the activation of PAR2 by kallikrein (a tryptic enzyme) related proteases was also shown in epidermal keratinocytes [71] which further argue for the impact of the pathway in pruriceptive itch.…”

Geschlechtsspezifische Unterschiede bei chronischem Pruritus

“…In klinischen Studien klagten Frauen häufi ger über Schmerzen, die länger andauerten und intensiver waren als bei Männern (Unruh 1996). In experimentellen Studien zu diesem Thema wiesen Frauen eine niedrigere Schmerzschwelle (Riley et al 1998) (Kleyn et al 2012;Papoiu et al 2012). Der lentiforme Nucleus nimmt dabei eine modulierende Rolle im sog.…”

Le prurit : des avancées physiopathologiques considérables

“…L'activation de ces récepteurs ne s'accompagne d'ailleurs pas d'une papule oedémateuse, contrairement à celle qui accompagne la réaction à l'activation des récepteurs de l'histamine. Elle est suivie par l'activation de neurones différents des neurones histaminergiques dans la moelle épinière [13], puis dans le cerveau [14]. Ce n'est que dans un deuxième degré de différenciation avec les nocicepteurs est encore l'objet de débats [4].…”

“…Ainsi, le cortex somato-sensoriel, le cortex pariétal, des aires motrices (cortex moteur primaire, aire motrice supplémentaire, cortex pré-moteur), le cortex préfrontal, le gyrus cingulaire antérieur, l'insula ou le mésencéphale sont activés en cas de prurit. Le claustrum, l'insula, les ganglions basaux, le putamen et le thalamus sont plus activés par le cowhage que par l'histamine [14]. Le processing cérébral du prurit est très sensible à la température [30].…”