Recent progress in unraveling central nervous system processing of itch sensation

Abstract

Itch is the major symptom of many allergic or inflammatory skin diseases, yet it is still difficult to measure objectively. This article shows and updates the development and approaches of central nervous system investigation of itch.Human neuroimaging studies on the physiology and pathophysiology of itch sensation have been hampered by the lack of a reproducible "on-off" stimulus. Short-term alternating temperature modulation of histamine-induced itch has recently been shown to provide on-off characteristics.Recent studies with functional magnetic resonance imaging demonstrate that itch sensation in healthy volunteers is processed by a network of brain regions contributing to the encoding of sensory, emotional, attentional, evaluative, and motivational aspects of itch.

Figure 1

Biphasic stimulus model using 32°C stimulation to decrease and 25°C stimulation to increase histamine-induced itch. The red/blue columns represent the mean itch intensity (VAS range, 0-100) of 9 healthy volunteers obtained every 4 seconds during the 20 seconds of the 32°C stimulation (red columns were numbered 1-5) and during the 20 seconds of the 25°C stimulation period (blue columns were numbered 6-10). Two sessions, each with 14 consecutive cycles of 32°C followed by 25°C stimulation, were applied. The yellow line represents the scratch threshold (33% itch intensity). Asterisks indicate significant differences between rating intervals. **P < 0.01, ***P < 0.001. From Pfab et al[13].

Figure 2

The increase of histamine-induced itch during the first 8 seconds of the 25°C stimulation periods (as compared with saline) is associated with an increase (red) and decrease (blue) of activation in various brain structures subserving sensory, emotional, cognitive, and motivational aspects of itch processing. As an example, the averaged relative fMRI BOLD signal of all subjects during 20 seconds of the 25°C stimulation period is presented: for the pre-SMA region with increased and the cingulate cortex with decreased activation in comparison with saline. DLPFC indicates dorsolateral prefrontal cortex; IPC, inferior parietal cortex; MFC, medial frontal cortex; OFC, orbitofrontal cortex; R, right side of the brain. From Valet et al[14].