Evidence suggests that galanin and its receptors including GalR1 are involved in the modulation of nociception. To understand the contributions of this galanin receptor subtype to the analgesic effect of galanin, we systematically examined the nociception phenotype of the GalR1 knockout (KO) mice. (1) Baseline thresholds: Thermal escape latencies and tactile thresholds of the hind paws were not different between the GalR1 KO and wild type (WT) mice. (2) Thermal injury evoked hyperalgesia: Thermal injury (52 degrees C, 45 s) to one hind paw resulted in a reduction in the thermal escape latency as compared to the uninjured paw. The right/left difference score was significantly greater in the KO (5.9 +/- 0.8 s) than for the WT (2.8 +/- 0.7 s) indicating a greater hyperalgesia. (3) Formalin-induced flinching: Formalin paw injection (2.5%/20 microl) produced a two-phase flinching in both GalR1 KO and WT groups, that was detected by an automated flinching sensor device. Phase II flinching of KO (1510 +/- 90) was slightly greater than that observed for WT (1290 +/- 126), but the difference is not statistically significant. (4) Nerve injury evoked allodynia: Tactile thresholds were assessed prior to and at intervals up to 21 days after left L5 spinal nerve ligation and transection. In both GalR1 KO and WT mice, nerve injury caused thresholds to fall to 0.2-0.3g though 11 days. On days 14-21, GalR1 KO animals showed a significant recovery as compared to WT. In summary, GalR1 KO mice showed no difference from WT with respect to acute nociception, but showed a modest tendency towards increased hyperalgesia after tissue injury and inflammation. These results are consistent with a regulatory effect of galanin at GalR1 receptors on nociceptive processing.