Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 11 December 2007
Vol. 2007, Issue 416, p. tw449
[DOI: 10.1126/stke.4162007tw449]


Neurobiology Pain in the Brain

L. Bryan Ray

Science, Science’s STKE, AAAS, Washington, DC 20005, USA

Delaney et al. provide new insights into signaling mechanisms that may help explain the integration of pain with stress reactions and with cognitive and emotional processing of pain signals in the brain. The discoveries come from an analysis of neurons in the central amygdala, a brain region where emotional responses to sensory stimuli are derived. Neurons carrying nociceptive information from a region known as the parabranchial nucleus make large synapses on cells of the central amygdala. Neurotransmission at these sites in rat brain slices was inhibited by noradrenaline, which is released by noradrenergic afferent neurons in the region. Electrophysiological experiments showed that noradrenaline acted presynaptically and appeared not to affect the probability of vesicle release but rather to limit the number of active release sites within the synapse. Experiments with inhibitors indicated that the noradrenaline acted at {alpha}2-adrenergic receptors coupled to Gi- or Go-type heterotrimeric guanine nucleotide-binding proteins (G proteins). Loading of presynaptic terminals with a membrane-permeable peptide that binds to G protein β{gamma} subunits inhibited the effects of noradrenaline, implicating Gβ{gamma} subunits in the process. Imaging of intracellular calcium concentrations with fluorescent dye showed that noradrenaline’s effects were independent of calcium concentrations. Thus, the Gβ{gamma} subunits appeared not to act by modulating channel activity but possibly by interacting with the vesicle release machinery. The actions of exogenous noradrenaline were also reproduced in experiments where release of noradrenaline from endogenous neurons was electrically stimulated. Tully et al. point out in commentary on the paper that this calcium-independent regulation might be particularly appropriate to reduce painful sensations during stressful situations that cause release of noradrenaline. Repetitive neuronal firing might gradually increase intracellular calcium concentrations sufficiently to overcome calcium-mediated inhibitory mechanisms, whereas the noradrenaline effect should be maintained even in the presence of rapid firing of presynaptic neurons.

A. J. Delaney, J. W. Crane, P. Sah, Noradrenaline modulates transmission at a central synapse by a presynaptic mechanism. Neuron 56, 880-892 (2007). [PubMed]

K. Tully, Y. Li, V. Y. Bolshakov, Keeping in check painful synapses in central amygdala. Neuron 56, 757-759 (2007). [PubMed]

Citation: L. B. Ray, Pain in the Brain. Sci. STKE 2007, tw449 (2007).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882