Direct and Indirect Nociceptive Input from the Trigeminal Dorsal Horn to Pain-Modulating Neurons in the Rostral Ventromedial Medulla.

The brain is able to amplify or suppress nociceptive signals by means of descending projections to the spinal and trigeminal dorsal horns from the rostral ventromedial medulla (RVM). Two physiologically defined cell classes within RVM, "ON-cells" and "OFF-cells," respectively facilitate and inhibit nociceptive transmission. However, sensory pathways through which nociceptive input drives changes in RVM cell activity are only now being defined. We recently showed that indirect inputs from the dorsal horn via the parabrachial complex (PB) convey nociceptive information to RVM. The purpose of the present study was to determine whether there are also direct dorsal horn inputs to RVM pain-modulating neurons. We focused on the trigeminal dorsal horn, which conveys sensory input from the face and head, and used a combination of single-cell recording with optogenetic activation and inhibition of projections to RVM and PB from the trigeminal interpolaris-caudalis transition zone (Vi/Vc) in male and female rats. We determined that a direct projection from ventral Vi/Vc to RVM carries nociceptive information to RVM pain-modulating neurons. This projection included a GABAergic component, which could contribute to nociceptive inhibition of OFF-cells. This approach also revealed a parallel, indirect, relay of trigeminal information to RVM via PB. Activation of the indirect pathway through PB produced a more sustained response in RVM compared with activation of the direct projection from Vi/Vc. These data demonstrate that a direct trigeminal output conveys nociceptive information to RVM pain-modulating neurons with a parallel indirect pathway through the parabrachial complex.