Studies Explain Why That Itch Needs Scratching

The itch-scratch cycle in humans tracked to specific regions of the brain, including areas related to reward, pain sensation, and addiction, functional brain imaging studies showed. The imaging results showed different neural activation patterns associated with itching versus scratching and with active scratching versus passive scratching performed by an observer. The findings, combined with other research reported here at the Society for Investigative Dermatology meeting, improve the understanding of the itch-scratch cycle to develop more effective therapies for itching conditions, including psoriasis and atopic dermatitis. Activation of brain areas previously linked to addiction and the formation of strong emotional attachments appears to "underline the hedonistic aspects of scratching," Alexandru D. Papoiu, MD, PhD, of Wake Forest University in Winston-Salem, N.C., and colleagues reported in a poster presentation. "These findings highlight the addictive nature of the itch-scratch cycle and suggest a role for the dopaminergic system in the central nervous system in modulating itch relief. Functional imaging studies in relation to pruritus could be further designed to develop an effective therapy in the future," they added. Previous studies of brain processing related to the itch-scratch cycle involved interventions that mimicked scratching. Real scratching constitutes a conscious, voluntary, motor response that is continuously adjusted by means of a neural feedback system, Papoiu and colleagues noted. Feedback loops assess receptive inputs and "appreciate the reward" afforded by scratching. Using 3-D functional MRI of the brain, investigators performed a study to visualize the key mechanisms and actions involved in itch relief. Specifically, they sought to capture: Where the decision to scratch occurs How motions are adjusted in response to itch relief The pleasurability of scratching Patterns of brain processing associated with self-scratching versus passive scratching Prior to investigating the itch-scratch cycle, investigators obtained several control images for comparison. They induced itching by exposing the forearm of volunteers to cowhage, a tropical woody vine with pods covered with barbed hairs. For active scratching the volunteers were instructed to use only the tips of their fingers and to try to avoid all other movement. Passive scratching was performed by observers using a cytology brush. The resulting MR images showed that active scratching more effectively relieved itch than did passive scratching, as reflected in more extensive deactivation of the anterior cingulate cortex, prefrontal cortex, insula, and lentiform nucleus. Involvement of the reward system was reflected in deactivation of the ventral tegmentum from the brain and the raphé nucleus by active scratching in comparison to itching. In contrast, passive scratching was associated with deactivation of the anterior cingulate cortex, the medial orbitofrontal cortex, caudate nucleus, and the nucleus accumbens. Another study reported at SID provided the first look into the genetics associated with itch. For the past 4 years researchers have studied itching behavior in a colony of Rhesus macaques with chronic itch. Investigators correlated the observational data with skin innervation and dermal expression patterns of the itch-specific mediator gastrin-releasing peptide (GRP). Using skin and spinal-cord tissue, Leigh Nattkemper, also of Wake Forest University, and colleagues found increased expression of GRP in lichenified (heavily scratched) versus nonlichenified skin, which correlated with increased expression of GRP receptor (GRPR) in the spinal cord of animals that chronically scratched versus those that did not. "Current experimental approaches to investigate the pathogenesis of chronic pruritus are largely limited to rodent models," Nattkemper and colleagues stated in a poster presentation. "This is the first study to show that the itch-specific receptor GRPR and its ligand GRP are linked to chronic itch in primates." A third report at the SID meeting provided details of a clinical investigation into variations in itch perception and the relief afforded by scratching. After induction of itching by cowhage exposure, 18 volunteers rated itch intensity and the pleasurability of scratching using a visual analog scale. The forearm, ankle, and back were tested separately. The results showed that higher baseline itch was associated with increased itch reduction by scratching at all three sites. For the forearm and ankle, higher itch during scratching correlated with increased pleasurability. "Pleasurability paralleled the curve of itch reduction for the back and forearm," Shawn G. Kwatra, also at Wake Forest University, and colleagues reported. "However, scratching pleasurability at the ankle remained elevated and only slightly decreased while itch was diminishing." "There are topographical differences in itch intensity, the effectiveness of scratching in relieving itch, and the associated pleasurability," they added. "Itch was more intensely perceived at the ankle, while scratching attenuated itch most effectively on the back."