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

BACKGROUND: 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. AIM: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.