Dopamine reuptake inhibition in the rostral agranular insular cortex produces antinociception

We provide evidence for an antinociceptive effect of dopamine in the rat ce rebral cortex that is mediated through descending nociceptive inhibition of spinal neurons. Injection of the dopamine reuptake inhibitor GBR-12935 in the rostral agranular insular cortex (RAIC), a cortical area that receives a dense dopaminergic projection and is involved in descending antinocicepti on (Burkey et al., 1996), resulted in dose-dependent inhibition of formalin -induced nociceptive behavior, without any alteration of motor function. In jection of the dopamine reuptake inhibitor in the surrounding cortical area s had no effect on nociceptive behaviors. GBR-12935 also produced a reducti on in noxious stimulus-induced c-fos expression in nociceptive areas of the spinal dorsal horn, suggesting that dopamine in the RAIC acts in part thro ugh descending antinociception. Electrophysiological recording from single wide dynamic range-type spinal dorsal horn neurons confirmed the descending nociceptive inhibitory effect. GBR-12935 in the RAIC significantly reduced neuronal responses evoked by noxious thermal stimulation of the skin, an e ffect that was reversed by local administration of the selective D1 recepto r antagonist SCH-23390. Finally, administration of SCH-23390 alone in the R AIC decreased paw withdrawal latencies from noxious heat, suggesting that d opamine acts tonically in the cortex to inhibit nociception.