Acute and chronic pain affect a significant amount of people across the US every year. Thus, the development of effective analgesics free of serious side effects has been a major challenging area of medicine. The development of effective analgesics to combat pain has been slowed by a lack of progress in understanding of the development and physiology of the pain pathway. To this end, the long-term objective of this proposal is to understand the factors and mechanisms regulating the development of the nociceptive pathway. Thus, we describe a series of aims to investigate the role of calcium-permeable kainate receptors in synapse formation between rat nociceptive dorsal root ganglion and spinal cord dorsal horn neurons. In the first aim, we set resolve the presence of these receptors at the growth cone of DRG neurons and determine whether they play any role in growth cone dynamics by calcium-imaging techniques.
In aim 2, we propose to establish the time course of synapse formation and the effects of pharmacological blockade of these receptors on synapse formation by using electrophysiology and immunocytochemistry. Finally, we propose to directly test their role in synapse formation by overexpressing and silencing their genes in vitro. ? ?
| Joseph, Donald J; Williams, Damian J; MacDermott, Amy B (2011) Modulation of neurite outgrowth by activation of calcium-permeable kainate receptors expressed by rat nociceptive-like dorsal root ganglion neurons. Dev Neurobiol 71:818-35 |
| Joseph, Donald J; Choudhury, Papiya; Macdermott, Amy B (2010) An in vitro assay system for studying synapse formation between nociceptive dorsal root ganglion and dorsal horn neurons. J Neurosci Methods 189:197-204 |
