Functional tracing of medial nociceptive pathways using activity-dependent manganese-enhanced MRI

Manganese ion (Mn2+) was used as a paramagnetic contrast agent in T1-weighted magnetic resonance imaging (MRI) images. They enter neural cells though voltage-gated calcium channels and are activity-dependently transported along axons and across synapses. The aim of the present study was to investigate the nociceptive medial thalamus projection in rats by activity-dependent manganese-enhanced magnetic resonance imaging (MEMRI). Rats under urethane and α-chloralose anesthesia were microinjected with manganese chloride (MnCl2, 120 mmol/L, iontophoretically with a 5-μA current for 15 min) into the right medial thalamus. Innocuous (at a 50-μA intensity for 0.2 ms) or noxious (at a 5-mA intensity for 2 ms) electrical stimuli were applied through a pair of needles in the left forepaw pads once every 6 s for 5 h. Enhanced transport of Mn2+ were found in the anterior cingulate cortex, midcingulate cortex, retrosplenial cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala in the noxious-stimulated group. Enhancements in the anterior cingulate cortex, midcingulate cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala, but not the retrosplenial cortex, were attenuated by an intraperitoneal injection of morphine (5 mg/kg and 1 mg/kg/h, intraperitoneal). These results indicate that a combination of MEMRI with activity-induced manganese-dependent contrast is useful for delineating functional connections in the pain pathway.