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Abstract Background The synaptic and cellular mechanisms of pain-related central sensitization in the spinal cord are not fully understood yet. Calcitonin gene-related peptide (CGRP) has been identified as an important molecule in spinal nociceptive processing and ensuing behavioral responses, but its contribution to synaptic plasticity, cellular mechanisms and site of action in the spinal cord remain to be determined. Here we address the role of CGRP in synaptic plasticity in the spinal dorsal horn in a model of arthritic pain. Results Whole-cell current- and voltage-clamp recordings were made from substantia gelatinosa (SG) neurons in spinal cord slices from control rats and arthritic rats (> 6 h postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents in the dorsal root near the dorsal root entry zone. Neurons in slices from arthritic rats showed increased synaptic transmission and excitability compared to controls. A selective CGRP1 receptor antagonist (CGRP8-37) reversed synaptic plasticity in neurons from arthritic rats but had no significant effect on normal transmission. CGRP facilitated synaptic transmission in the arthritis pain model more strongly than under normal conditions where both facilitatory and inhibitory effects were observed. CGRP also increased neuronal excitability. Miniature EPSC analysis suggested a post- rather than pre-synaptic mechanism of CGRP action. Conclusion This study is the first to show synaptic plasticity in the spinal dorsal horn in a model of arthritic pain that involves a postsynaptic action of CGRP on SG neurons.

Abstract Background The latero-capsular part of the central nucleus of the amygdala (CeLC) is the target of the spino-parabrachio-amygdaloid pain pathway. Our previous studies showed that CeLC neurons develop synaptic plasticity and increased neuronal excitability in the kaolin/carrageenan model of arthritic pain. These pain-related changes involve presynaptic group I metabotropic glutamate receptors (mGluRs) and postsynaptic NMDA and calcitonin gene-related peptide (CGRP1) receptors. Here we address the role of group II mGluRs. Results Whole-cell current- and voltage-clamp recordings were made from CeLC neurons in brain slices from control rats and arthritic rats (>6 h postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents from the pontine parabrachial (PB) area. A selective group II mGluR agonist (LY354740) decreased the amplitude of EPSCs more potently in CeLC neurons from arthritic rats (IC50 = 0.59 nM) than in control animals (IC50 = 15.0 nM). The inhibitory effect of LY354740 was reversed by a group II mGluR antagonist (EGLU) but not a GABAA receptor antagonist (bicuculline). LY354740 decreased frequency, but not amplitude, of miniature EPSCs in the presence of TTX. No significant changes of neuronal excitability measures (membrane slope conductance and action potential firing rate) were detected. Conclusion Our data suggest that group II mGluRs act presynaptically to modulate synaptic plasticity in the amygdala in a model of arthritic pain.

Introduction: Primary care in the United States faces unprecedented challenges from an aging population and the accompanying prevalence of chronic disease. In response, continuing medical education (CME) initiatives have begun to adopt the principles of performance improvement (PI) into their design, although currently there is a dearth of evidence from national initiatives supporting the effectiveness of this methodology. The specific aim of this study was to demonstrate the value of a national PI-CM E activity to improve the performance of physicians treating patients with diabetes. Methods: We analyzed data from the American Academy of Family Physicians' METRIC® PI-CME activity in a cohort of family physician learners. The study utilized the 3-stage design standard approved for PI-CME. Baseline and follow-up performance data across a range of clinical and systems-based measures were compared in aggregate. Results: Data were assessed for 509 learners who completed the activity. Statistically significant changes occurred both for self-assessment of a range of practice aspects and for diabetes care measures. Learners recognized that the organization of their practices had improved, and mechanisms were in place for better staff feedback, as well as aspects of patient self-management. Based on the clinical data obtained from 11 538 patient charts, 6 out of 8 diabetes measures were significantly improved. Discussion: The activity appears to have had a positive, measurable impact on the medical practice of learners and suggests that, when appropriately designed and executed, PI-CME on a national scale can be a useful vehicle to influence performance change in physicians and to inform future CME activities. [ABSTRACT FROM AUTHOR]