The development and/or maintenance of thermal and mechanical hyperalgesia and spontaneous pain in a variety of pain models; EphB1 receptors are necessary for the induction of phosphorylation of the NR2B subunit of the NMDA receptor and are Lomitapide Mesylate involved in the increase of c-fos expression in models of inflammatory pain and tissue injury and in microglial activation following PNL. EphB1 receptors, together with other Eph receptors, play an important role in neuronal development, therefore it was important to establish that EphB1 KO mice were normal in terms of development of nociceptive pathways and nociception, in order to be suitable in models for the study of the modulation of pain processing. This had not been examined in previous studies using these mice. Since pain sensitivity in animal models is measured through behavioural tests dependent on a motor response, it was also important to test na? ��ve KO mice in comparison to WT 
littermate in a motor test, particular in light of findings indicating that EphB1 KO exhibit neuronal loss in the substantia nigra. We found no indication that this loss affected the response to acute noxious stimuli using a variety of tests, including thermal and mechanical stimuli, or to the first phase of the formalin test, reflecting acute tissue damage. Gross anatomical abnormalities were also absent from both the DRG and the dorsal horn of the spinal cord. Similarly electrophysiological recording at the cord dorsum, measuring the spatial distribution and amplitudes of the CAPs and FPs following sciatic nerve stimulation, did not reveal any difference between WT and EphB1 KO mice in terms of somatotopic organisation of sensory projections in the spinal cord. Although the presence of developmental defects in glutamatergic synapses in the hippocampus of transgenic EphB2 KO mice remains unclear, it is possible that in single mutants compensatory mechanisms, due to the presence of other EphB receptors, which bind promiscuously to the same ephrinB ligands, may allow a comparatively normal development. We cannot however exclude the presence of subtle changes, for example at the level of the glutamatergic synapses of sensory afferents onto dorsal horn neurons, below the level of detection behaviourally. In this respect our finding of enhanced sural nerve evoked superficial dorsal horn FPs is of relevance in that it indicates such a change in the connectivity of Ab-fibres. Our simplest explanation for this finding draws on the changes Mepiroxol observed early postnatally in the rat where the predominant A-fibre innervation of the superficial dorsal horn at birth undergoes a dramatic, activity-dependent withdrawal of the nerve terminals to deeper layers over the first postnatal weeks. It is proposed here that such functional and structural reorganisation did not occur in EphB1KO mice. Further studies are needed to determine whether inhibitory or excitatory interneurons, projection neurons or both, are involved in this refinement process. Although this change in the connectivity of A fibres in the sural nerve is of considerable interest in view of the guidance role of Eph receptors during development, it had no demonstrable impact on the behavioural tests we employed, or on the gross anatomical connectivity of C and Ad fibres. Another possible explanation for the enhanced synaptic transmission we observed could be a change in the electrophysiological properties of the large diameter Ab-fibre, as described in DRG neurons for a rat model of osteoarthritic pain and more recently in a neuropathic pain model.