Mechanisms underlying the contribution of chemokines to pain are not completely understood. Lymphotactin (XCL1) signals via the receptor XCR1 but its role in pain is unknown. In this study, we hypothesize a contribution of XCL1 to excitatory activity in the spinal cord and trigeminal systems. We used electrophysiology in adult rat trigeminal brainstem and lumbar spinal cord slices in vitro to determine the effects of XCL1 on subnucleus caudalis (Vc) and substantia gelatinosa (SG) excitability. All procedures were carried out under anaesthesia (pentobarbital, 50 mg/kg i.p.) and accorded with UK Home Office legislation. Extracellular recordings were made in Vc and SG using transverse brainstem and spinal cord slices, respectively. Superfusion with XCL1 (2h) enhanced a form of rhythmic activity that can be quantified using spectral analysis. XCL1 significantly increased power area and power amplitude parameters in Vc and SG (all p < 0.05) indicating an enhanced level of intrinsic excitability. This is similar to 4-aminopyridine-induced augmented excitability in spinal cord which is an accepted model of enhanced central excitability. These data suggest a role for XCL1 in central sensitization which has been associated to chronic pain.