Spinal bombesin-recognized neurones mediate more nonhistaminergic than histaminergic sensation of itch in mice

Abstract

There may be distinct pathways for transmission of histaminergic and nonhistaminergic itch, but all scratching behaviours elicited by histamine-dependent and histamine-independent pruritogens are diminished when spinal bombesin-recognized neurones are ablated. To investigate whether there is a difference in transmission of spinal itch signals between histamine-induced itch and nonhistamine-induced itch after neurotoxic destruction of spinal bombesin-recognized neurones. To ascertain the different relevance of spinal bombesin-recognized neurones in transmission of itch signals between these two classes of pruritogens, we determined the distribution of Fos-positive cells in the dorsal horn of spinal cord after stimulation with histamine (500 μg/site) and chloroquine (200 μg/site) in mice with spinal bombesin-recognized neurones ablated by intrathecal injection of bombesin-saporin (400 ng/5 μL). We found that after stimulation with both histamine and chloroquine, fewer Fos-positive cells were present in mice treated with bombesin-saporin compared with those treated with saporin alone. The reduction in Fos expression was greater with chloroquine than with histamine, and the distribution of Fos-positive cells was also different. We used biotin-labelled isolectin (IB)4, which labels one subset of C-fibres, and found that the percentages of Fos-positive cells in three areas (the dorsal to IB4-labelled region, the IB4-labelled region itself, and the ventral to IB4-labelled region) all changed significantly after intradermal injection of chloroquine, but not histamine, in mice treated with bombesin-saporin. These results suggest that spinal bombesin-recognized neurones are critical to both the histamine-dependent and histamine-independent pathways for itch, and that they mediate more nonhistaminergic than histaminergic sensation of itch in mice.