Fractalkine is the only member of the CX3C subgroup of chemokines. It exists as a trans-membrane protein that can be cleaved to release its chemokine domain. Fractalkine activates only one known receptor, CX3CR1, which has been shown to be present in the dorsal root ganglion (DRG). Using semi-quantitative RT-PCR analysis we have shown that CX3CR1 mRNA is present in the intact adult mouse DRG and that levels increase 5.8-fold at 1 week and 6.2-fold at 3 weeks after sciatic nerve axotomy. Immunohistochemistry of the DRG has shown that CX3CR1 and fractalkine proteins are present predominantly in glia and neurons respectively. These results suggested that fractalkine-CX3CR1 might be involved in the adaptive response of the PNS to injury, and thus may play a role in modulating nociception and/or neuronal regeneration after injury. To investigate the effect of fractalkine on pain-related behaviour, it was administered intra-sciatically into mice (1). Fractalkine had no effect on either thermal or mechano-sensory pain behaviours in intact mice. However, when administered at the time of spared nerve injury (SNI) surgery (a model of neuropathic pain) (2), it attenuated mechano-sensory allodynia. Intra-sciatic fractalkine also reduced nociceptive behaviour in response to intra-dermal formalin (3). Studies of CX3CR1 knockout and wildtype mice demonstrated that in naive animals the knockouts have lower withdrawal thresholds to both thermal and mechanical stimulation. Furthermore, following SNI (2), the knockouts developed more allodynia than wildtypes. These results imply that CX3CR1 activation by fractalkine has an anti-nociceptive role after nerve injury when expression of the receptor is markedly up-regulated. Before surgery, animals were anaesthetised with Hypnorm:Hypnovel:water at a ratio of 1:1:2 and a dose of 5 μl/g. Animals were killed humanely 2 weeks after surgery.