Their depth profiles in the dorsal horn as this would provide direct evidence of a developmentally �C based shift in their sites of termination and/or or their synaptic strength. Following our initial work demonstrating an involvement of EphB receptors-ephrins interaction in modulation of pain processing in the spinal cord, a growing number of other studies has provided evidence supporting a role of EphB receptors in a variety of short-term inflammatory and longer-term, chronic pain models. Initially, the unequivocal identification of the specific EphB receptor involved had been impossible, due to the lack of suitable reagents and in particular specific agonists and antagonists. A study by Han et al., performed on one of the strains of EphB1 KO mice used here, confirmed the hypothesis of an involvement of EphB1 receptors in neuropathic pain and in physical dependence to morphine, comparing the behavioural responses of EphB1 KO, heterozygous and WT mice. In their study, a complete lack of development of thermal hyperalgesia was observed in EphB1 KO mice in the CCI model. Here, we examine the EphB1 KO mice studied by Han et al. in a number of other models, including short-term and long-term inflammation, tissue damage and PNL. Even if the molecular and cellular 4-(Benzyloxy)phenol mechanisms underlying hypersensitivity in experimental Folinic acid calcium salt pentahydrate models of pain have not been completely clarified, it is clear that different molecular and cellular mechanisms underlie hypersensitivity in different pain models, and also mechanical and thermal hyperalgesia in the same model; for example, with regard to neuropathic pain, it has been shown that there are significant differences in the mechanisms leading to chronic pain in different models, and in the mechanisms leading to the induction of thermal and mechanical hyperalgesia. It is therefore important to establish if and to what extent EphB1 receptors contribute to thermal and mechanical hyperalgesia, as well as spontaneous pain behaviour, in pain states of different aetiology. In a number of models we observed a complete lack of development of mechanical and thermal hyperalgesia, as we expected on the basis of previous findings obtained in rats treated with the EphB receptor blocker EphB1-Fc or in EphB1 KO mice. However, in the CFA-induced inflammatory pain model hyperalgesia and allodynia developed almost normally in KO mice, but recovery was accelerated. This is particularly interesting because due to its duration the CFA model would arguably be one of the most clinically relevant. Furthermore, this finding was partially replicated in the PLN model of neuropathic pain where thermal hyperalgesia developed almost normally in KO mice, but recovery was accelerated. The results obtained in the CFA and PNL models indicate that EphB1 receptors play a significant role in maintaining sensitisation hence emphasising their importance as a potential therapeutic target. The behavioural findings reported here are evidence of a crucial role of EphB1 receptors in the onset and/or maintenance of thermal and mechanical hypersensitivity in a variety of models of pain, but what are the specific cellular and molecular mechanisms involved? Notwithstanding the number of differences in the molecular and cellular changes they induce, in all of the models we have used, a supposed common mechanism is represented by classical central sensitisation, an activity-dependent increase in the strength of synaptic 
transmission between primary sensory afferents and dorsal horn neurons.