Effect And Neuronal Mechanism Of Stimulation Of Midbrain Periaqueductal Gray On Itch

Itch is an unpleasant sensation that causes scratch or the desire to scratch. Severe itch is always accompanied with different kinds of diseases, including skin diseases, thyroid disorder, and acquired immune deficiency syndrome. Unfortunately, there exists few effective diagnosis or treatment for itch. It is because the psychological and pathological process of itch is not clear. A lot of researches concentrate on ascending pathways of itch while there is little about its descending pathways. Studies of descending control of itch signals will allow a better understanding of neuronal mechanisms of itch, as well as providing methods and basic theories for the treatment of the refractory itch. When a large number of studies demonstrate that midbrain periaqueductal gray matter (PAG) plays an important role in the modulation of pain sensation, PAG may also participate the descending inhibition of itch as indicated in some studies. However, there is no report examining the effects and neuronal mechanisms of stimulating midbrain PAG on itch.The present study aims to explore the effect and neuronal mechanism of stimulating midbrain PAG on itch behavior in mice, with intracerebral electrical stimulation and drug injection approaches. The results are as follows:1. We examined the effect of electrical stimulation of PAG on histamine-induced scratching behavior of mice. We found that electrical stimulation of dPAG produced an inhibition of the scratch behaviors. The number of scratches in control group was114(±48, n=8) within the first30minutes after subcutaneous administration of histamine to the back of the neck. The number of scratches in the dPAG stimulation group was46(±8, n=8),-60%reduction. These results indicate that PAG is involved in the modulation of itch sensation.2. To study the mechanism underlying the inhibition of itch by electrical stimulation of dPAG in mice, the role of5-HT receptors in dPAG mediated inhibition of itch was examined. Metergoline, a selective antagonist of5-HT was locally administered to dPAG through an implanted cannula before subcutaneous injection of histamine and then electrical stimulations were delivered to the dPAG. We found that the number of scratches in electrical-stimulation group was39.8%of control (±8.1, n=6); metergoline tended to reverse the effect of electrical stimulation. Thus, in the presence of the5-HT antagonist, the number of scratches following electrical stimulation was65.7%of control (±14.3%, n=6), suggesting a role of5-HT in mediating dPAG modulation of itch, although this effect did not reach statistical significance. However, this finding needs to be confirmed with additional experiments.In conclusion, electrical stimulation of PAG reduces histamine-induced scratch behavior in mice, suggesting a role of PAG in modulation of itch signal processing.