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

Manganese ion (Mn(2+)) 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 (MnCl(2), 120mmol/L, iontophoretically with a 5-μA current for 15min) into the right medial thalamus. Innocuous (at a 50-μA intensity for 0.2ms) or noxious (at a 5-mA intensity for 2ms) electrical stimuli were applied through a pair of needles in the left forepaw pads once every 6s for 5h. Enhanced transport of Mn(2+) 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 (5mg/kg and 1mg/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. Noxious stimulation induced enhancement of manganese ion transportation from medial thalamus to cingulate cortex and medial striatum, but not motor cortex. A combination of manganese-enhanced magnetic resonance imaging with activity-dependent contrast is useful for delineating functional connections of the medial pain pathway.