The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC) provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc). This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP) test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation.
Cortical mechanisms that regulate acute or chronic pain remain poorly understood. The prefrontal cortex (PFC) exerts crucial control of sensory and affective behaviors. Recent studies show that activation of the projections from the PFC to the nucleus accumbens (NAc), an important pathway in the brain’s reward circuitry, can produce inhibition of both sensory and affective components of pain. However, it is unclear whether this circuit is endogenously engaged in pain regulation. To answer this question, we disrupted this circuit using an optogenetic strategy. We expressed halorhodopsin in pyramidal neurons from the PFC, and then selectively inhibited the axonal projection from these neurons to neurons in the NAc core. Our results reveal that inhibition of the PFC or its projection to the NAc, heightens both sensory and affective symptoms of acute pain in naïve rats. Inhibition of this corticostriatal pathway also increased nociceptive sensitivity and the aversive response in a chronic neuropathic pain model. Finally, corticostriatal inhibition resulted in a similar aversive phenotype as chronic pain. These results strongly suggest that the projection from the PFC to the NAc plays an important role in endogenous pain regulation, and its impairment contributes to the pathology of chronic pain.
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