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The rat model of cervical dorsal root injury mimics the avulsion of dorsal roots in humans following brachial plexus injury, a condition that leads to debilitating sensory disturbances and intractable neuropathic pain that is not amenable to repair. This injury disrupts sensory inputs from the dorsal roots to the spinal cord and the damaged axons do not regenerate across the PNS-CNS interface, the dorsal root entry zone. This thesis investigated the role of OECs for repairing DRI-associated neuropathic pain, which has never been previously explored. Chapter 2 of this thesis characterised two DRI models, a partial (2-root) or complete (4-root) deafferentation of the rat forepaw. The 2-root animals developed persistent allodynia and hyperalgesia, whereas in the 4-root DRI, in contrast, reduced sensation (desensitisation) was found within the affected forepaw. The degree of deficits on performing complex, skilled forepaw movements was proportional to the severity of DRI. Sensory control of forepaw movements was permanently abolishes in animals with 4-root DRI. With the goal of repairing DRI-associated neuropathic pain, the efficacy of genetically modified OECs that carry a novel GDNF construct was examined. These modified GDNF-OECs were able to produce GDNF in vitro, however, died rapidly and failed to yield long term GDNF expression after both acute and delayed transplantation into the DRI spinal cord. Unmodified plain OECs were then used. The results show that delayed transplantation of OECs attenuated the development of DRI-associated allodynia and hyperalgesia. Central reorganisations occurred within the dorsal horn following DRI, including reduction in the area of deep dorsal horn, permanent depletion of IB4-labeled axons and restoration of CGRP-labelled afferents in the denervated superficial laminae. The development of neuropathic pain is suggested to be mediated by the aberrant expansion of large myelinated VGLUT1-positive afferents into the superficial laminae, which normally receive nociceptive inputs. The effect of OECs on modulating nociception seems to be mediated by factors other than inhibition of afferent sprouting. In conclusion, the results in this thesis demonstrated the potential effect of OECs for modulating DRI-associated neuropathic pain. This finding could have clinical applicability for resistant pain sequelae resulting from neurotrauma.

To investigate the roles of different dorsal spinal pathways in controlling movements in rats, I performed lesions of specific spinal pathways and measured the behaviour abilities of rats using different sensorimotor behavioural tests. The first experiment was designed to understand the contribution of sensory pathways traveling in the dorsal funiculus during locomotion and skilled movements using sensitive behavioural tests. I demonstrated that ascending sensory fibers play an important role during overground locomotion and contribute to skilled forelimb movements. The second experiment compared the differences in sensorimotor abilities caused by dorsal funicular lesions performed at two different levels of rat spinal cord. My results showed that the pathways present in the cervical and thoracic dorsal funiculus exert different functional effects over control of limb movement during locomotion. The third experiment investigated the compensatory potential of dorsal funicular pathways after dorsolateral funicular injuries in rats. My results showed that dorsal funicular pathways do not compensate for loss of dorsolateral pathways during the execution of locomotor tasks, though there is indirect evidence that rats with dorsolateral funicular lesions might rely more on ascending sensory pathways in the dorsolateral funiculus during skilled forelimb movements. Finally, the fourth experiment was designed to investigate the compensation from dorsolateral funicular pathways after injuries to pyramidal tract in rats. I demonstrated that pathways running in the spinal dorsolateral funiculus do provide compensatory input to spinal circuitry to maintain skilled reaching abilities after lesions of the pyramidal tract but these same pathways do not appear to compensate during either overground locomotion or skilled locomotion. Thus, this compensatory response is task-specific. These results highlight the fact that behavioural context determines the nature of compensation from spared pathways after spinal cord injuries.

To investigate the roles of different dorsal spinal pathways in controlling movements in rats, I performed lesions of specific spinal pathways and measured the behaviour abilities of rats using different sensorimotor behavioural tests. The first experiment was designed to understand the contribution of sensory pathways traveling in the dorsal funiculus during locomotion and skilled movements using sensitive behavioural tests. I demonstrated that ascending sensory fibers play an important role during overground locomotion and contribute to skilled forelimb movements. The second experiment compared the differences in sensorimotor abilities caused by dorsal funicular lesions performed at two different levels of rat spinal cord. My results showed that the pathways present in the cervical and thoracic dorsal funiculus exert different functional effects over control of limb movement during locomotion. The third experiment investigated the compensatory potential of dorsal funicular pathways after dorsolateral funicular injuries in rats. My results showed that dorsal funicular pathways do not compensate for loss of dorsolateral pathways during the execution of locomotor tasks, though there is indirect evidence that rats with dorsolateral funicular lesions might rely more on ascending sensory pathways in the dorsolateral funiculus during skilled forelimb movements. Finally, the fourth experiment was designed to investigate the compensation from dorsolateral funicular pathways after injuries to pyramidal tract in rats. I demonstrated that pathways running in the spinal dorsolateral funiculus do provide compensatory input to spinal circuitry to maintain skilled reaching abilities after lesions of the pyramidal tract but these same pathways do not appear to compensate during either overground locomotion or skilled locomotion. Thus, this compensatory response is task-specific. These results highlight the fact that behavioural context determines the nature of compensation from spared pathways after spinal cord injuries.