The Translational Studies of Pain: From Spinal Neurones to Human Perception

摘要: The discovery of new treatments for chronic pain relies on the detection pre-clinical targets and progression to successful clinical trials. In order improve this transition reliable translational models must be identified, based mechanisms that underlie symptoms pain. This thesis aimed validate use 3 potential models: topical capsaicin, ultraviolet irradiation (UVB) UVB rekindling. Furthermore, using a mechanism approach treatment, modulation capsaicin induced sensitisation was explored in animals humans. characterise rats, vivo electrophysiological recordings were made from single unit dorsal horn wide dynamic range neurones. Evoked responses thermal, mechanical electrical stimulation quantified. To complement animal studies, full QST profiling undertaken healthy human volunteers. Assessments thresholds made, as well numerical ratings sub supra threshold stimuli, best compare these results with rodent data. All tested evoked similar sensory changes across species, each used infer peripheral central components. Sensory by included hypersensitivity accompanied facilitation Aδ fibre range. These are reflective both sensitisation. prevented pre-treatment adenosine receptor 1 (A1R) agonist, CPA. appeared strictly model, resulting no secondary or receptive field expansion. On other hand, rekindling model showed clear signs engaging mechanisms, including thermal allodynia, brush Aβ responses. Overall, we confirmed short-term consequences, may mimic certain pathophysiologies, could engaged quantified rats volunteers response engagement number clinically relevant phenomena, such inflammation/ driving modifications. As will useful investigating inflammatory assessing analgesic efficacy novel medications.