Abstract
BackgroundPsychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis. The rodent prefrontal cortex (PFC) including cingulate areas is also related to the affective dimension of pain. We previously reported PFC nociceptive responses inhibited by inputs from the amygdala, such as with dopamine (DA) D2 receptor (D2R) blockers, to show decreased effect on amygdala projections. In this study, we examined whether direct projections from the ventral tegmental area (VTA) to the PFC affect nociceptive responses in the PFC.ResultsHigh frequency stimulation (HFS, 50 Hz, 30 s) delivered to the VTA produced long-lasting suppression (LLS) of nociceptive responses in the rat PFC including cingulate and prelimbic areas. Nociceptive responses evoked by mechanical pressure stimulation (2 s duration at 500 g constant force) applied to the tails of urethane-anesthetized rats were recorded using extracellular unit recording methods in the PFC. HFS delivered to the VTA, which has been reported to increase DA concentrations in the PFC, significantly suppressed nociceptive responses. The LLS of nociceptive responses persisted for about 30 minutes and recovered to the control level within 60 min after HFS. We also demonstrated local microinjection of a selective D2 agonist of DA receptors to induce LLS of mechanical nociceptive responses, while a D2 but not a D1 antagonist impaired the LLS evoked by HFS. In contrast, DA depletion by a 6-hydroxydopamine injection or a low concentration of DA induced by a κ-opiate receptor agonist injected into the VTA had minimal effect on nociceptive responses in the PFC.ConclusionHFS delivered to VTA inhibited nociceptive responses for a long period in PFC. DA D2R activation mediated by local D2 agonist injection also induced LLS of mechanical nociceptive responses. The mesocortical DA system may modify PFC nociceptive responses via D2 activity.
Highlights
Psychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis
HFS delivered to the ventral tegmental area (VTA) decreased nociceptive responses in the prefrontal cortex (PFC) High frequency stimulation (HFS, 50 Hz, 30 s) delivered to the VTA impaired PFC nociceptive responses evoked by mechanical stimulation applied to the rat tail (11 units/9 rats) (Figure 1B)
HFS delivered to the VTA inhibited nociceptive responses recorded in the PFC
Summary
Psychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis. We examined whether direct projections from the ventral tegmental area (VTA) to the PFC affect nociceptive responses in the PFC. In clinical reports on PD, patients frequently complain of neuropathic or central pain before motor disorders [12,13,14] These clinical reports indicate that the brain DA level modifies pain sensations. We determined whether lower DA concentration changes in the VTA induced by 6-OHDA lesions alter nociceptive responses in the PFC. We examined effects of a κ-opiate receptor agonist injected into VTA on nociceptive responses. A κ-opiate receptor agonist injected into VTA inhibited only DA neurons projecting to PFC and reduced DA level in PFC [19]
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