Abstract
Functional magnetic resonance imaging (fMRI) in rodents enables non-invasive studies of brain function in response to peripheral input or at rest. In this study we describe a thermal stimulation paradigm using infrared laser diodes to apply noxious heat to the forepaw of mice in order to study nociceptive processing. Stimulation at 45 and 46°C led to robust BOLD signal changes in various brain structures including the somatosensory cortices and the thalamus. The BOLD signal amplitude scaled with the temperature applied but not with the area irradiated by the laser beam. To demonstrate the specificity of the paradigm for assessing nociceptive signaling we administered the quaternary lidocaine derivative QX-314 to the forepaws, which due to its positive charge cannot readily cross biological membranes. However, upon activation of TRPV1 channels following the administration of capsaicin the BOLD signal was largely abolished, indicative of a selective block of the C-fiber nociceptors due to QX-314 having entered the cells via the now open TRPV1 channels. This demonstrates that the cerebral BOLD response to thermal noxious paw stimulation is specifically mediated by C-fibers.
Highlights
Functional magnetic resonance imaging in animals enables non-invasive studies of brain function, e.g. involving the sensory system
Capsaicin activates and opens the TRPV1 channel, allowing the QX-314 molecule to enter the cell and block the sodium channels by binding to a specific site located at its intracellular domain, inhibiting the propagation of action potentials [19]. In this Functional magnetic resonance imaging (fMRI) study we showed that pretreating mice with QX-314 in combination with capsaicin led to abolishment of the blood oxygen level dependent (BOLD) fMRI signal elicited by thermal stimulation, while administration of either compound alone did not affect the signal amplitude
BOLD Signal Changes Correlate with the Thermal Stimulation Paradigm
Summary
Functional magnetic resonance imaging (fMRI) in animals enables non-invasive studies of brain function, e.g. involving the sensory system. FMRI of Pain Processing in Mouse Brain Elicited by Thermal Stimulation stimulus, which would lead to the activation of neurons. In view of these potential drawbacks, at the aim of this study was to establish a more physiological stimulation paradigm with better controllable parameters using an infrared laser to induce noxious stimulation by local heating of the forepaws. Thermal stimulation in mouse fMRI should provide a powerful tool to investigate various pathologies and mechanisms of pain disorders, taking advantage of the many available transgenic mouse models It has the additional benefit of being a translational method, as laser heat stimulation has been used in clinical fMRI studies [8]. This protocol led to reproducible changes in the blood oxygen level dependent (BOLD) signal intensity in the various brain areas including those associated with pain processing, with signal amplitudes increasing as a function of skin temperature
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