The ventral striatum is implicated in the analgesic effect of mood changes.

BACKGROUND: The ventral striatum, particularly the nucleus accumbens, is commonly associated with the processing of reward and positive stimuli, positive affect as well as antinociceptive processes. OBJECTIVES: The present study examined whether the ventral striatum is implicated in analgesia resulting from positive mood change induced by pleasant odours. METHODS: Functional magnetic resonance imaging studies were conducted in healthy individuals receiving painful heat stimuli in the presence of pleasant or unpleasant odours, which were used to induce positive and negative mood states. Ventral striatum activity was examined in the two mood states. RESULTS: For most subjects, pleasant odours improved mood and reduced pain unpleasantness perception relative to unpleasant odours. In the pleasant odour condition, the maximum activation of both the left and right ventral striatum was positively correlated with the amount of pain reduction. Furthermore, the left and right ventral striatum activations positively covaried with one another, and the right ventral striatum activation positively correlated with that in the periaqueductal grey matter. Both ventral striatum activations negatively covaried with the activation of the right mediodorsal thalamus, left dorsal anterior cingulate cortex, left medial prefrontal cortex and right ventrolateral prefrontal cortex. CONCLUSIONS: Because both the mediodorsal thalamus and anterior cingulate are involved in pain affect perception, and activation within the prefrontal areas and periaqueductal grey matter were previously shown to correlate with mood-related pain modulation, it is concluded that the ventral striatum is likely implicated in the analgesic effect of positive mood changes induced by pleasant odours on pain unpleasantness.

The beta3 subunit of the Na+,K+-ATPase mediates variable nociceptive sensitivity in the formalin test.

It is widely appreciated that there is significant inter-individual variability in pain sensitivity, yet only a handful of contributing genetic variants have been identified. Computational genetic mapping and quantitative trait locus analysis suggested that variation within the gene coding for the beta3 subunit of the Na+,K+-ATPase pump (Atp1b3) contributes to inter-strain differences in the early phase formalin pain behavior. Significant strain differences in Atp1b3 gene expression, beta3 protein expression, and biophysical properties of the Na+,K+ pump in dorsal root ganglia neurons from resistant (A/J) and sensitive (C57BL/6J) mouse strains supported the genetic prediction. Furthermore, in vivo siRNA knockdown of the beta3 subunit produced strain-specific changes in the early phase pain response, completely rescuing the strain difference. These findings indicate that the beta3 subunit of the Na+,K+-ATPase is a novel determinant of nociceptive sensitivity and further supports the notion that pain variability genes can have very selective effects on individual pain modalities.