Neuropsychiatry Laboratory

Lab head: Maxwell Bennett
Location: M02 - Mallet Street Campus

Lab members: M Bennett (head)

Pain representation in the brain: the astrocytic model for fMRI and the interpretation of images

Primary supervisor: Maxwell Bennett

Pain of superficial (cutaneous) origin is sharp and restricted, whereas pain of deep origin (muscle and viscera) is dull and diffuse. Using functional magnetic resonance (fMRI), major differences in the regions of the brain 'activated' in these different conditions have been noted by L. Henderson and his colleagues. These include regions associated with the emotions (perigenual cingulate cortex), with stimulus localization and intensity (somatosensory cortex) and motor control (motor cortex and cingulate motor area). However, the identification of regions as 'activated' depends on what fMRI is measuring, which is changes in the blood oxygen level development (BOLD). It is now known that changes in blood flow at the level of capillaries and arterioles is under the control of the endfeet of astrocytes whose processes enfold of the order of 10,000 synapses. Adenosine, nitric oxide and epoxyeicosatrenoic acids (EETs) are the substances released at the interface between astrocyte endfeet and the endothelial cells of blood vessels. These substances have powerful relaxing effects on the smooth muscle of blood vessels, leading to vasodilation and an increase in blood flow.

The question examined in this project is:- what is the mechanism by which activity at synapses is conveyed to blood vessels through astrocytes, and to what extent the resultant BOLD signal changes can be said to reflect "activated" brain regions? Without determination of this mechanism and the factors which perturb it, use of fMRI to investigate pain pathways in the brain must be carried out with some caution.

L. Henderson et al., (2006) Pain 120: 286-296.
A. Arthurs & S. Boniface (2002) Trends in Neuroscience 25: 27-31.
A. Volterra & J. Meldoles (2005) Nature Reviews Neuroscience 6: 626- .
C. Pepplatt & D. Attwell (2004) Nature 431: 137- .
R. Kochler et al., (2006) Journal of Applied Physiology 100: 302-317.

Discipline: Physiology