It is well-established that the amygdala, a forebrain multinuclear structure, plays a crucial role in emotional? behaviors such as fear, anxiety, and stress. It has recently been proposed that the amygdala, in particular the? central nucleus (CeA), is also involved in the modulation of pain sensation. Evidence from anatomical,? behavioral, and physiological studies support the hypothesis that the amygdala serves as a neural pain center? that integrates noxious sensory information and emotions. Preliminary results from our lab and others have? demonstrated that electrophysiological changes occur in the central nucleus of the amygdala during periods of? persistent pain. For this reason, we have been performing studies aimed at elucidating the signaling cascades? involved in the modulation of pain sensation by the amygdala. Our preliminary studies indicate that? inflammation of one hindpaw induces acute pain in the injected paw, and after a period of several hours, also? in the uninjured contralateral paw. Interestingly, the timing of the onset of this contralateral hypersensitivity? coincides with the activation of the extracellular signal regulated kinase (ERK) in the right amygdala,? specifically in the laterocapsular subdivision of the central nucleus (CeC). Our preliminary data support the? hypothesis that ERK activation in the right (but not left) CeC underlies the development of generalized pain? hypersensitivity after inflammation. However, there are still a number of unanswered questions regarding the? role of amygdala ERK activation in pain modulation. The present application will address some of these issues.? In the first aim, we will test whether the right lateralized ERK activation in the CeC is physiologically relevant in? multiple pain models.
The second aim of the proposal utilizes patch clamp recordings from brain slices to test? the hypothesis that ERK activation leads to acute modulation of neuronal excitability and/or synaptic? transmission in the CeC. These studies will lay important groundwork for future investigations of the? importance of amygdala ERK signaling in pain sensitization.
| Kolber, Benedict J; Montana, Michael C; Carrasquillo, Yarimar et al. (2010) Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior. J Neurosci 30:8203-13 |
| Ji, Ru-Rong; Gereau 4th, Robert W; Malcangio, Marzia et al. (2009) MAP kinase and pain. Brain Res Rev 60:135-48 |
| Carrasquillo, Yarimar; Gereau 4th, Robert W (2008) Hemispheric lateralization of a molecular signal for pain modulation in the amygdala. Mol Pain 4:24 |
