Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior

Benedict J. Kolber, Michael C. Montana, Yarimar Carrasquillo, Jian Xu, Stephen F. Heinemann, Louis J. Muglia, Robert W. Gereau IV

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78 Scopus citations

Abstract

The central nucleus of the amygdala (CeA) has been identified as a site of nociceptive processing important for sensitization induced by peripheral injury. However, the cellular signaling components underlying this function remain unknown. Here, we identify metabotropic glutamate receptor 5 (mGluR5) as an integral component of nociceptive processing in the CeA. Pharmacological activation of mGluRs with (R,S)-3,5-dihydroxyphenylglycine (DHPG) in the CeA of mice is sufficient to induce peripheral hypersensitivity in the absence of injury. DHPG-induced peripheral hypersensitivity is reduced via pharmacological blockade of mGluR5 or genetic disruption of mGluR5. Furthermore, pharmacological blockade or conditional deletion ofmGluR5in theCeAabrogates inflammation-induced hypersensitivity, demonstrating the necessity of mGluR5 in CeA-mediated pain modulation. Moreover, we demonstrate that phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2) is downstream of mGluR5 activation in the CeA and is necessary for the full expression of peripheral inflammation-induced behavioral sensitization. Finally, we present evidence of right hemispheric lateralization of mGluR5 modulation of amygdalar nociceptive processing. We demonstrate that unilateral pharmacological activation of mGluR5 in the CeA produces distinct behavioral responses depending on whether the right or left amygdala is injected. We also demonstrate significantly higher levels of mGluR5 expression in the right amygdala compared with the left under baseline conditions, suggesting a potential mechanism for right hemispheric lateralization of amygdala function in pain processing. Together, these results establish an integral role for mGluR5 and ERK1/2 in nociceptive processing in the CeA.

Original languageEnglish (US)
Pages (from-to)8203-8213
Number of pages11
JournalJournal of Neuroscience
Volume30
Issue number24
DOIs
StatePublished - Jun 16 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kolber, B. J., Montana, M. C., Carrasquillo, Y., Xu, J., Heinemann, S. F., Muglia, L. J., & Gereau IV, R. W. (2010). Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior. Journal of Neuroscience, 30(24), 8203-8213. https://doi.org/10.1523/JNEUROSCI.1216-10.2010