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Itch is a multidimensional experience involving various brain regions associated with sensory perception and emotion, as well as an urge to scratch employing the motor system. Scratch temporarily relieves itch sensation in healthy subjects. However, in patients with chronic itch, rather than inhibit, scratch may aggravate itch. Patients with chronic itch, such as those with atopic dermatitis, experience severe itch and a strong desire to scratch. This urge to scratch is the driving force underlying the formation of the itch‐scratch‐cycle, an addictive and vicious cycle in chronic itch patients. This vicious itch‐scratch behaviour and various types of addiction (henceforth, including recreational drug use) were shown to share common sensory mechanisms. Abnormalities have been observed in central neural circuits, including the reward, motivation/drive, control and learning/memory circuits, as well as other brain systems. Reward systems, including the ventral tegmental area (VTA), nucleus accumbens (NAc) and striatum, are important for brain processing of both addiction and itch. In addition to reward, addicted individuals can experience severe disruptions in motor control, cognitive awareness, executive function, learning/memory and even emotional functions. Findings showing that addiction and itch share a common neurobiological foundation could have important mechanistic and therapeutic implications. Here we propose that similar neuroadaptations exist in addiction and chronic itch patients. [ABSTRACT FROM AUTHOR]

Abstract: Nerve growth factor (NGF) was reported to be increased in the serum and skin of atopic dermatitis (AD) patients, to the extent that serum nerve growth factor levels were proposed to serve as a marker of disease severity. We studied NGF levels in the serum and dermis using skin microdialysis and attempted to correlate them with disease severity. We also examined if potential differences between morning and evening levels of NGF can explain the phenomenon of nocturnal itch. In addition, neurogenic inflammation and itch were induced using histamine iontophoresis in lesional and non-lesional skin and the effect of experimental itch on dermal NGF concentration was examined. We found that systemic (serum) and eczematous skin levels of NGF in AD are significantly lower in comparison to healthy controls. Serum NGF decreases from morning to late afternoon in both groups. Interestingly, serum NGF levels were correlated to disease severity in the morning in AD, although the NGF concentration in AD were significantly lower than in the healthy group. The local itch and neurogenic inflammation induction via experimental histamine reduced local NGF levels in the eczema and non-lesional skin in atopics, but not in the healthy controls, where it was slightly increased. The higher the clinical severity of the eczema, a significantly less pronounced effect of neurogenic inflammation on the local levels of NGF was found. The availability of measurable NGF might be reduced by a higher expression of NGF receptors. The fluctuations of NGF levels during the day suggest a complex modulation of this neurotrophin, potentially linked to stress or to an altered neurophysiological mechanism. [Copyright &y& Elsevier]

In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of ΔFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of ΔFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress. Image 1 • The rewarding effect can be evoked by scratching under itch stimuli. • Pharmacogenetic suppression of dopaminergic neurons decreases scratching. • Scratching under itch stimuli activates mesolimbic dopamine neurons. • The restriction of scratching activates PVN-CRH neurons. [ABSTRACT FROM AUTHOR]