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The AMPA Receptor in Descending Circuitry: Role in Activity-Dependent Plasticity

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Neurons throughout the rostral ventromedial medulla (RVM), a pivotal structure in descending pain modulatory circuitry, express the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors. Recent studies suggest that glutamatergic neurotransmission, through AMPA receptors, plays a key role in the development of activity-dependent plasticity in the RVM in response to persistent inflammatory hyperalgesia. Peripheral inflammation induces a time-dependent enhancement of AMPA-produced descending inhibition, an upregulation of AMPA receptor GluR1 subunit expression associated with an increased neuronal activation in the RVM, and an increase in the level of GluR1 phosphorylation. These convergent findings suggest that neuronal activation and GluR1 expression/activation contribute to the enhanced descending pain modulation after inflammatory hyperalgesia. The increased AMPA neurotransmission in the RVM, together with an increase in N-methyl-D-aspartate receptor activation, leads to increased excitability and activity-dependent plasticity in the brain stem pain modulatory circuitry.
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Keywords: AMPA; Descending modulation; GluR1; Hyperalgesia; Inflammation; Phosphoserine 831 GluR1; Rostral ventromedial medulla

Document Type: Review Article

Affiliations: 1: Department of Organizational Systems & Adult Health, School of Nursing, University of Maryland, Baltimore, MD 21201, USA 2: Department of Biomedical Sciences, Dental School, and Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA

Publication date: 01 February 2005

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  • Reviews in Analgesia (formerly Analgesia) is an international journal that publishes in English original reviews by experts on topics related to the basic mechanisms and therapeutics of pain relief. Reviews are invited that focus on pain mechanisms, endogenous mediators of pain, mechanisms of analgesia, and the synthesis, testing, or mechanism of action study of known or experimental analgesic compounds-including nonanalgesic and side effect endpoints and abuse liability. In addition, reviews of clinical studies or practice are invited that help elucidate the mechanism of action of known analgesic drugs, or that report on the use of experimental compounds or combinations. Reviews on new or standard methodological approaches, statistical analyses, and theoretical or mathematical treatments are also invited.
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