Project update: Probing nociception in near physiological mice fMRI Abstract: Combining mouse genetics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. The aim of this presentation is to introduce an enabling methodology to permit the study of large-scale brain circuits in pain processing using near-physiological mouse fMRI. In contrast to established subcutaneous electrostimulation paradigms, the proposed method focuses on the reproducible application of brief, mild noxious heat stimuli (46 °C /14 sec) to the plantar hindpaw of anesthetized mice. This permits research into clinically relevant forms of chronic pain, such as hyperalgesia and allodynia. The method comprises further advances in technical, procedural and data processing tools for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying this method to wildtype mice resulted in BOLD activation patterns closely resembling those observed in humans – a basic requirement for translational studies. Status: confirmed