Effects of pruritogens and algogens on rostral ventromedial medullary ON and OFF cells

Abstract

Rostroventromedial medulla (RVM) ON and OFF cells are thought to facilitate and inhibit spinal nociceptive transmission, respectively. However, it is unknown how ON and OFF cells respond to pruritic stimuli or how they contribute to descending modulation of spinal itch signaling. In pentobarbital sodium-anesthetized mice, single-unit recordings were made in RVM from ON and OFF cells identified by their respective increase or decrease in firing that occurred just before nocifensive hindlimb withdrawal elicited by paw pinch. Of RVM ON cells, 75% (21/28) were excited by intradermal histamine, 50% (10/20) by intradermal chloroquine, and 75% (27/36) by intradermal capsaicin. Most chemically responsive units also responded to a scratch stimulus applied to the injected hindpaw. Few ON cells responded to intradermal injection of vehicle (saline: 5/32; Tween 2/17) but still responded to scratching. For OFF cells, intradermal histamine and scratching inhibited 32% (6/19) with no effect of histamine in the remainder. Intradermal chloroquine inhibited 44% (4/9) and intradermal capsaicin inhibited 61% (11/18) of OFF cells. Few OFF cells were affected by vehicles (Tween: 1 inhibited, 7 unaffected; saline: 3 excited, 1 inhibited, 8 unaffected). Both ON and OFF cells that responded to one chemical usually also responded to others, whereas units unresponsive to the first-tested chemical tended not to respond to others. These results indicate that ascending pruriceptive signals activate RVM ON cells and inhibit RVM OFF cells. These effects are considered to facilitate and disinhibit spinal pain transmission, respectively. It is currently not clear if spinal itch transmission is similarly modulated.NEW & NOTEWORTHY The rostroventromedial medulla (RVM) contains ON and OFF cells that are, respectively, excited and inhibited by noxious stimuli and have descending projections that facilitate and inhibit spinal nociceptive transmission. Most RVM ON cells were excited, and OFF cells inhibited, by intradermal injection of the pruritogens histamine and chloroquine, as well as the algogen capsaicin. These results indicate that itchy stimuli activate RVM neurons that presumably give rise to descending modulation of spinal itch transmission.