Descending control of spinal nociception that originates from the midbrain periaqueductal grey (PAG) is an important determinant of the pain experience. We have recently shown that cyclooxygenase-1 (COX-1) regulates activity at the level of the PAG and that COX-1 inhibition exerts a preferential effect on C- versus A-nociceptor-evoked withdrawal reflexes (Leith et al, 2007). The current study investigated whether this differential control of C- versus A-nociceptor-evoked activity may be mediated in the spinal dorsal horn. Extracellular recordings were made from wide dynamic range deep dorsal horn neurones (n=18) with receptive fields on the hindpaw dorsum in alphadolone/alphaxalone-anaesthetised (~20mg.kg^-1.hr^-1, i.v.) male Wistar rats (280-300g; n=18). At 8 minute intervals, either fast (7.5°C.s^-1, 30-57°C) or slow (2.5°C.s^-1, 30-55°C) rates of heating were applied to the receptive field to preferentially activate Aδ- or C-heat nociceptors respectively (Yeomans et al, 1996a; 1996b; McMullan et al, 2004). Neuronal responses were recorded for 30min before and 65min after administration of the COX-1 inhibitor SC560 (50nM; 300nl volume; n=14) or vehicle (phosphate-buffered saline; n=4) into the ventrolateral-PAG. Afferent input to each cell was characterised by percutaneous electrical stimulation of the receptive field at suprathreshold (1.5 and 3.0 times threshold) intensity for C-fibre activation and the degree of C-fibre input was quantified. SC560 significantly increased the firing threshold of neurones to both fast and slow heat ramps (to a peak of 127±3% and 145±11% of control threshold respectively, mean±S.E.M., ANOVA, both p<0.01, n=8-9; overall effect on firing threshold (measured as area under the curve (AUC) over the timecourse 0-65min) 186±25min.°C and 211±36min.°C respectively, mean±S.E.M., ANOVA, both p<0.01) compared to vehicle. Peak change in firing threshold post-SC560 and overall effect on firing threshold were not significantly different between fast and slow heat ramps (p=0.0911 and p=0.5791 respectively, t-test, n=8-9). A significant positive correlation was found between the change in firing threshold (both peak threshold and overall effect on firing threshold) produced by SC560 and the degree of C-fibre afferent input to the neurones (r=0.5795, p<0.05 and r=0.6625, p<0.01 respectively, Spearman’s rank correlation). The data show that COX-1 inhibition in the ventrolateral-PAG inhibits the responses of wide dynamic range dorsal horn neurones to A- and C-heat nociceptor stimulation and suggests that the degree of descending control from the PAG on individual neurones may be dependent on the extent of their C-fibre innervation.