Galanin is known to have both excitatory and inhibitory effects in the CNS, effects that are known to be concentration dependent (Wiesenfeld-Hallin et al. 1989). Galanin (Gal) activates two G protein coupled receptors (GalR) in DRG neurones, GalR1 and GalR2 (Waters & Krause, 1999). Thus Gal may have differing functional effects on different DRG neuronal populations. Recently Gal was shown to have both inhibitory and facilitatory effects on knee joint afferent responses to noxious joint movement (Heppelmann et al. 2000), supporting this hypothesis. The aim of this study was to determine the effect of close arterial Gal administration on mechanically- and cold-evoked responses of cutaneous afferents. As Gal peptide is rapidly degraded in vivo in the systemic circulation, repeated measurements could be made in the same afferents. Recordings were made from 16 single cutaneous high threshold mechanosensitive (HTM) fibres from teased filaments of the saphenous nerve, in deeply anaesthetised male Wistar rats (250-350g, sodium pentobarbital ~20mg kg^-1 h^-1 i.v.). Conduction velocities were determined by electrical stimulation of the receptive field (RF); all were <5ms^-1. Mechanical thresholds for activation were determined using graded von Frey (VF) hairs (0.2-180g). Responses to cold were activated by skin cooling by acetone. Data are medians ± semi-interquartile range unless otherwise noted. Galanin (10^-4M) altered mechanically evoked activity in 13/16 HTMs, increasing firing frequency in 12 and decreasing activity in 1 of the units (p<0.05 Chi squared cf. saline vehicle). In the HTM population in which activity was increased, planned comparisons showed that Gal significantly increased responses of HTMs to 4g (0+0.1 cont., 0.23 ± 1Hz Gal, p=0.03, Wilcoxon signed rank) and 10g (0.2+0.6 cont., 0.7 ± 1.8Hz Gal, p=0.02, Wilcoxon signed rank). 6 HTM units also responded to cooling, increasing their firing rate in response to cutaneous acetone (2.4±1.1 cont, vs 3.2±1.1 Hz, acetone; p<0.01 ANOVA + Bonferroni; means ± s.e.m.). This was significantly attenuated by Gal (2.2±1.0 Hz acetone + Gal: p<0.001 ANOVA + Bonferroni; mean ± s.e.m.). Thus, in cutaneous high threshold mechanonociceptors, 10^-4M galanin exerts excitatory effects by enhancing their responses to non-noxious stimuli (4-10g). In HTMs also responsive to cold, however, 10^-4M Gal inhibits activity evoked by skin cooling. We suggest that the differential effects of galanin on different sensory stimuli reflects differences in primary afferent GalR receptor expression. Future work will concentrate on the effects of GalR2 specific agonists on primary afferents.